Acute and Chronic Pain Management

## Outpatient Management of Chronic Pain

*Franzes Anne Z. Liongson, Rina Bhalodi, Christopher McCarthy, Sanjay V. Menghani and Ajaz Siddiqui*

## **Abstract**

In this chapter, we provide an overview of the most current techniques in the evaluation, diagnosis, and treatment of pain in the outpatient setting. We performed a targeted literature review by searching for the terms such as "chronic pain" and "pain management." Relevant articles were cited, and findings were described in the chapter text. Additionally, we supplemented our review with images from the Spine and Pain Associates' offices at St. Luke's University Health Network (SLUHN) in Bethlehem, PA, as well as medical illustrations by our authors. We begin the review with a description of pain—its definition, components, complexity, and classifications and then provide a stepwise outline of the pharmacologic approach beyond nonsteroidal anti-inflammatory drugs before delving into newer interventional pain management procedures. Subsequently, this chapter is not comprehensive as it does not provide extensive discussion on older, more established procedures such as epidural steroid injections as well as practices falling out of favor such as discograms and neurolysis. Instead, we focus on newer subacute to chronic nonmalignant pain interventions. Finally, we attempt to highlight future directions of the growing field. Overall, we provide an overview of the management of chronic by providing insights into updates to chronic pain management.

**Keywords:** chronic pain, interventional pain, outpatient medicine, opioids, narcotics

## **1. Introduction**

Pain is a complicated, subjective sensation that results from physical stimuli as well as psychological factors. Pain can vary in location, severity, quality, and consistency. It can occur in response to either physical injury or emotional distress. While there are multiple definitions that have been proposed, the most widely accepted definition of pain, as described by Cohen *et al.* in 2018 is *"*an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" [1].

The pain response is generated by the propagation of nociceptive signals by neurons in the central nervous system (CNS) and peripheral nervous system (PNS) in response to noxious stimuli. Fundamentally, the mechanism of pain comprises detection of noxious stimuli, transduction of noxious stimuli into electrochemical signals, transmission of the electrical signals by neuronal pathways, and modulation through the nervous system

to produce the sensation of pain. This process is facilitated by the axons, also known as nerve fibers, which propagate the nociceptive signals to the central nervous system [2].

Pain begins with detection of primary noxious stimuli. Research shows that Transient Receptor Potential (TRP) superfamily of ion channels play a vital role in the detection of pain [3]. Following detection, signals are sent along axons of sensory neurons toward the CNS. The nerve fiber types recognized to play a major role in pain include Aδ and C fibers, two types of primary afferent (sensory) nociceptors. Type Aδ fibers are myelinated nerve fibers with fast conduction speeds that are activated by thermal and mechanical stimuli. They are associated with prickling pain of short duration. Type C fibers are unmyelinated nerve fibers with slow conduction speeds that are activated by thermal, mechanical, and chemical stimuli. They are associated with poorly localized, dull pain. Some C-fibers may also be peptidergic, which means that they express neuropeptides such as substance P (SP), neurokinins, and calcitonin gene-related peptide (CGRP) [4]. There is association between specific TRP channels and specific types of nerve fibers; for example, TRPV1, which is the receptor for capsaicin is associated with sensory neurons having Type C fiber axons [5]. Alternatively, TRPM8, which responds to cold sensation and menthol, is associated with sensory neurons that have Aδ and C fibers [6]. Nerve fibers carry the action potential, an electrochemical signal generated in response to the detected noxious stimuli.

The action potential generated by nociceptors in response to noxious stimuli is transmitted between neurons and culminates with the release of neurotransmitters. Common neurotransmitters and their effects on pain are listed in **Table 1**.


#### **Table 1.**

*Neurotransmitters and their effects on pain.*

Neurotransmitters that act as inflammatory mediators include prostaglandins (PGE2, PGI2), leukotriene B4 (LTB4), nerve growth factor (NGF), bradykinin (BK), adenosine triphosphate (ATP), adenosine, tachykinins (substance P (SP), neurokinin A (NKA), and neurokinin B (NKB)), 5-hydroxytryptamine (5-HT), histamine, glutamate, norepinephrine (NE), and nitric oxide (NO). Neurotransmitters acting as non-inflammatory mediators include calcitonin generelated peptide (CGRP), gamma-aminobutyric acid (GABA), opioid peptides, glycine, and cannabinoids [7]. These various neurotransmitters are involved with pain transduction, transmission, and modulation, thus facilitating the mechanism of pain [8, 9].

## **2. Classification of pain**

## **2.1 Acute versus chronic pain**

Pain is classified as either acute or chronic. Acute pain begins suddenly, often due to an injury to the body. It can be caused by, but not limited to, broken bones, burns, sprains, wounds, falls, and medical procedures. Acute pain is not a disease and better classified as a symptom that indicates an inflammatory process that brings attention to tissue damage. Acute pain may affect more than the injured part of the body and can be debilitating due to loss of function, fatigue, or sleep deprivation. Generally, acute pain resolves within 3 months as the body heals. Acute pain can often be treated with the application of ice, analgesics, immobilization, and support bandages.

Acute pain can become chronic pain. Chronic pain is ongoing pain that lasts for more than 6 months and is usually much harder to diagnose and treat than acute pain. Chronic pain occurs when the physical condition causing acute pain remains unresolved in cases such as cancer or arthritis. Chronic pain also occurs when the nervous system is damaged or malfunctions, sending pain signals to the brain without a specific cause. In 2012, the Journal of Pain estimated that the cost of chronic pain was around \$600 billion dollars when taking healthcare costs and lowered productivity into account [10]. In 2019, the National Institute for Health Services found that more than 50% of Americans were experiencing chronic pain, and back pain was the lead contributor at 39% [11–13]. Common causes of chronic pain include joint pain due to degenerative damage and overuse, migraines, neuropathic pain, and cancer. More in-depth discussion of chronic pain conditions and treatment options is in the following section of this chapter and summarized in **Table 2**.

## **2.2 Nociceptive versus neuropathic pain**

The two most common types of pain are nociceptive pain and neuropathic pain. Nociceptive pain is caused by tissue damage or injury to the skin, bones, muscles, or joints. Examples include pain from a broken arm, a sprained ankle, a puncture wound, or a fall.

Neuropathic pain (commonly described as "pins and needles") is a numbing or shooting pain that results from damage to the nerves. Common causes of nerve damage resulting in neuropathic pain include uncontrolled diabetes, infections, surgical procedures, radiation treatments, and physical trauma.


#### **Table 2.**

*Chronic pain conditions and treatment options.*

## **3. Chronic pain conditions and their conservative management**

## **3.1 Complex regional pain syndrome**

Complex regional pain syndrome (CRPS) is broadly defined as prolonged and excess inflammation and pain following an injury. CRPS has both acute and chronic forms. CRPS is characterized by spontaneous or excessive pain following mild touch or allodynia. Other symptoms include changes in skin temperature, color and swelling. CRPS usually improves over time and severe and prolonged cases are rare but profoundly disabling. Most CRPS is caused by improper function of the peripheral C-fiber nerves. Excess firing of these nerve fibers sends pain messages to the brain and triggers inflammation. Injuries in CRPS typically are subtle and may go unnoticed.

Early or mild cases of CRPS generally resolve on their own. Primary treatments include physical therapy, psychotherapy, and medications. Several classes of medications have been reported as effective for CRPS, but none are FDA approved. Medications include acetaminophen, NSAIDS, and topical anesthetics. Drugs used for other neuropathic pain conditions (discussed in further detail in subsequent sections

of this chapter) such as nortriptyline, gabapentin, pregabalin, amitriptyline, and duloxetine have also been shown to be effective. Corticosteroids such as prednisolone and methylprednisolone can be used to treat inflammation, swelling, and edema. Opioids such as oxycodone, morphine, hydrocodone and fentanyl may be required for the most severe cases.

## **3.2 Arthritis**

Arthritis is the swelling and tenderness of one or more joints. The main symptoms of arthritis are joint pain and stiffness, swelling, and decreased range of motion that typically worsens with age. The most common types of arthritis are osteoarthritis and rheumatoid arthritis. While osteoarthritis causes breakdown of cartilage, rheumatoid arthritis is a disease where the immune system attacks the lining of the joints. Treatments vary depending on the type of arthritis and focus on reducing symptoms and improving quality of life. Arthritis is usually diagnosed by physical examination. Analysis of body fluids can identify the type of arthritis. Imaging such as X-rays, CT, and MRI can detect problems within the joint causing symptoms.

Arthritis treatment focuses on relieving pain and improving joint function. The medications used to treat arthritis depend on the type of arthritis. NSAIDS such as ibuprofen and naproxen sodium can relieve pain and inflammation. Acetaminophen has been shown not to be as effective as NSAIDS for arthritis pain. Counterirritant ointments applied over the aching joint may interfere with the transmission of pain from the joint. Corticosteroid medications such as prednisone will reduce inflammation and pain and slow joint damage. Exercise can improve the range of motion, strengthen muscles, and reduce pain.

## **3.3 Fibromyalgia**

Fibromyalgia is characterized by widespread musculoskeletal pain, cognitive difficulties, tenderness, fatigue, numbness or tingling in the arms and legs, heightened sensitivity, sleep disturbances, and emotional and mental distress. Newer guidelines from the American College of Rheumatology require the main factor for diagnosis to be widespread pain throughout the body for at least 3 months. Fibromyalgia affects about 2% of the adult population. Symptoms often begin after a physical trauma or psychological stress. Women are more likely than men to develop fibromyalgia. Fibromyalgia coexists with tension headaches, chronic fatigue syndrome, TMJ, irritable bowel syndrome, postural tachycardia syndrome, depression, and anxiety. The pain, fatigue, and poor sleep quality can interfere with function at home and at work.

The cause of fibromyalgia is unknown; however, many researchers believe that fibromyalgia amplifies painful sensations by affecting the way the brain and spinal cord process signals. This involves the increase in levels of certain chemicals in the brain that signal pain. The brain pain receptors become sensitized and overreact to painful and non-painful signals. Risk factors include sex, genetics, infections, and physical or emotional trauma. Patients with arthritis and lupus are more likely to develop fibromyalgia.

Fibromyalgia is treated with both medications and lifestyle strategies. The main focus of treatment is to reduce pain and improve the quality of life. Common medications to reduce pain include pain relievers, antidepressants, and anti-seizure drugs. Over-the-counter (OTC) pain relievers such as acetaminophen, ibuprofen, or naproxen sodium may be helpful. Opioid medications are not recommended due to significant

side effects and addiction and may worsen pain over time. Duloxetine (Cymbalta) and milnacipran (Savella) are FDA approved for treating fibromyalgia and may ease pain and fatigue associated with fibromyalgia. Amitriptyline or the muscle relaxant cyclobenzaprine may be prescribed to promote sleep. The epilepsy drug gabapentin is sometimes used to reduce fibromyalgia symptoms. Pregabalin (Lyrica) is used to treat nerve pain and is FDA approved for treating pain caused by fibromyalgia.

Lifestyle changes include aerobic exercise and muscle strengthening exercises, stress management techniques such as meditation, yoga, and massage, sleep habits to improve the quality of sleep, and cognitive behavioral therapy (CBT) to treat underlying depression.

#### **3.4 Cancer pain**

Cancer pain is often caused by cancer compressing on or infiltrating a part of the body, diagnostic procedures, or treatments or from skin, nerve, or other tissue damage caused by hormone imbalance or immune response. Tumors cause pain by crushing or infiltrating tissue, triggering inflammation or infection, or releasing chemicals that stimulate pain. Invasion of the bone by cancer is the most common source of cancer pain. When tumors compress, invade, or inflame parts of the nervous system, they can cause pain. Chronic pain may be continuous or intermittent. Despite pain being adequately controlled by long-acting drugs, breakthrough pain may occasionally occur and is treated with fast-acting analgesics. The presence of cancer pain depends on the location and stage of the cancer. About half of the patients diagnosed with cancer are in pain at a given time and two-thirds of patients with advanced cancer experience debilitating pain. Cancer pain can be either eliminated or adequately controlled in about 80–90% of the cases. Unfortunately, nearly 50% of cancer patients receive suboptimal pain care.

Cancer pain treatment aims to relieve pain with minimal side effects. WHO guidelines recommend prompt administration of drugs when cancer pain occurs. Non-opioid medications such as paracetamol, dipyrone, non-steroidal anti-inflammatory drugs, or COX-2 inhibitors should be administered when pain is not severe. Refractory cancer pain may require more aggressive treatment with mild opioids such as codeine, dextropropoxyphene, dihydrocodeine, or tramadol. Mild opioids are replaced by stronger opioids such as morphine if pain control is still not adequate. More than half of patients with advanced cancer and pain will require strong opioids. Morphine is effective at relieving cancer pain although oxycodone shows superior tolerability and analgesic effect. Side effects of nausea and constipation are rarely severe enough to cause stopping treatment. Sedation and cognitive impairment usually occur with the initial dose and increase with the strength of the opioid. There is some evidence that buprenorphine is another opioid with some evidence of analgesic effect. Other medicines that can also relieve pain, including antidepressants, anti-seizure drugs, and steroids A nerve block procedure can be used to stop pain signals from being sent to the brain. In this procedure, a numbing medicine is injected around or into a nerve. Pain relief may also be enhanced through acupuncture, massage, physical therapy, relaxation exercises, meditation, and hypnosis.

#### **3.5 Chronic pelvic pain syndrome**

Chronic pelvic pain occurs in the abdomen, genital area, lower back, or thighs and lasts more than 6 months. The pain may become worse when urinating, having

#### *Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

intercourse, walking, or during menstrual periods. Chronic pelvic pain is often caused by irritable bowel syndrome, interstitial cystitis, pelvic floor dysfunction, endometriosis, pelvic injury, and ovarian cysts. Determining the cause of chronic pelvic pain often involves a process of elimination as many different disorders can result in pelvic pain. Pelvic exam can reveal signs of infection, abnormal growths, or tense pelvic floor muscles. Blood and urine tests can check for infections. Ultrasound is useful for detecting masses or cysts in the ovaries, uterus, and fallopian tubes. X-ray, CT scans, and MRI can detect abnormal structure and growths. Laparoscopy allows for a view of pelvic organs to check for abnormal tissues or signs of infection.

There are several treatments depending on the cause of pelvic pain. Hormone medications may relieve pelvic pain that coincides with a particular phase of the menstrual cycle and the hormonal changes that control ovulation and menstruation. Antibiotics can be prescribed for infections that are a source of pelvic pain. Antidepressant medications can be effective for chronic pelvic pain. TCAs such as amitriptyline and nortriptyline have been shown to relieve chronic pelvic pain even in the absence of depression. Physical therapy, neurostimulation, trigger point injections, and psychotherapy can also be an effective part of the treatment plan.

## **4. Traditional pharmacologic approaches to pain**

## **4.1 Opioids**

According to the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain, nonopioids are preferred to opioids for the treatment of chronic pain [14]. If pain cannot be adequately controlled with OTC medications, opioid therapy may be recommended for a limited time. The decision to initiate opioid therapy for the treatment of pain is challenging and should only be made after a thorough assessment has been performed to ascertain the complete nature of the pain, comorbid patient conditions, and pain treatments that have been trialed in the past. Opioids should be prescribed alongside both non-opioid medications and non-pharmacologic treatments and should be closely monitored as prolonged use is not recommended due to risks of addiction, tolerance, and misuse [15].

More than 191 million opioid prescriptions were dispensed to Americans in 2017. Thus, it is important to screen patients for mental illness and substance use disorders that would place them at increased risk for overdose. In an effort to reduce the risk of opioid addiction and misuse, medical societies including the CDC recommend utilizing risk reduction strategies, including written pain agreements prior to starting opioid treatment for chronic pain. These agreements provide opportunities to establish pain goals, discuss the risks and benefits of opioid therapy, and clearly outline the treatment plan that will be utilized to monitor and guide opioid use.

Opioids, sometimes referred to as narcotics, are strong painkillers derived from the opium poppy plant and are used to block pain signals between the brain and the body, providing immediate relief to intense pain by altering the brain's perception of pain. They may be prescribed for low back pain, neuropathic pain, or arthritis pain [14, 16]. Opioids act primarily by binding to the μ-opioid receptor (MOR) on the cell membrane of neurons. Respiratory depression is one of the most dangerous risks associated with opioids and in severe cases can cause apnea. The risk is higher if patients have underlying respiratory conditions such as asthma or sleep apnea. Constipation is also a common side effect associated with chronic opioid use.

Popular examples of opioids include hydrocodone, hydromorphone, methadone, fentanyl, meperidine, morphine, tramadol, and oxycodone. The most common drugs involved in prescription opioid overdose deaths include methadone, oxycodone, and hydrocodone. A recent study showed that 67% of patients who require opioid-based medications were also receiving one or more other prescription drugs. Adverse drug interaction events can be linked to polypharmacy. A recent analysis among chronic back pain patients on long-term opioid analgesics reported that the overall prevalence of drug–drug interactions (DDIs) was 27% [17].

There are numerous drugs that can interact with opioid medications. Several opioids (including codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are metabolized by the cytochrome P450 (CYP450) system and are associated with DDIs that either reduce opioid efficacy or exacerbate side effects. Morphine, oxymorphone, and hydromorphone are not metabolized by the CYP450 system and are generally involved in fewer DDIs. When prescribing opioids, it is important to remember that they can exacerbate sedation and respiratory when utilized alongside alcohol, anxiolytics, and hypnotics. Opioids can also interact with certain antibiotics, antidepressants, anti-seizure medications, antifungals, and antiretrovirals.

Tramadol is a commonly prescribed opioid that has analgesic properties as well as alternative mechanisms of action. Tramadol is found as a racemic mixture of two enantiomers that have synergistic effects: one enantiomer works as a selective μ agonist and inhibits serotonin reuptake, while the other enantiomer inhibits serotonin and norepinephrine reuptake [18]. Tramadol and its active metabolite (M1) inhibit ascending pain pathways by binding to μ receptors in the central nervous system [18]. Inhibition of reuptake of serotonin and norepinephrine by tramadol and M1 inhibit descending pain pathways to aid in pain relief [18]. It is important to take into consideration that the side effects of tramadol include seizures, NMS, and serotonin syndrome.

Buprenorphine offers a safer alternative for patients who require opioids to manage chronic pain, given the unique pharmacological properties that allow it to provide adequate analgesia with less abuse potential. As a long-acting partial μ receptor agonist and κ receptor antagonist, it leads to analgesia. High dose administration of buprenorphine leads to μ receptor antagonism, achieving the opposite effect. Combination of buprenorphine and naloxone, the pure μ receptor antagonist, is available as Suboxone [18]. The combinatory effects of Suboxone are designed to prevent illicit intravenous use.

#### **4.2 Non-opioid options for pain**

There are several well-known and well-utilized non-opioid approaches to pain management beyond non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Several examples include topical anesthetics, counterirritants, corticosteroids, muscle relaxants, anti-depressants, and anti-seizure medications. **Table 3** provides an overview of pharmacologic approaches and common side effects of each approach.

Topical anesthetics are valuable options in pain management as they achieve relief with a low risk of side effects and drug interactions. There are many formulations available such as creams, ointments, gels, lotions, and patches. Lidocaine 5% patch (Lidoderm) is also FDA approved for the treatment of postherpetic neuralgia. In addition to topical anesthetics, counterirritants (including salicylates, capsaicin, and menthol) can be utilized to provide local and temporary irritation that distracts and interrupts pain signals to the brain. Capsaicin, in the form of Qutenza, is FDA approved for the treatment of pain associated with postherpetic neuralgia.

## *Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*


#### **Table 3.**

*Common pharmacologic approaches to pain management with examples and common side effects.*

Steroids are powerful anti-inflammatory medications that can be taken orally or injected. Corticosteroids are used to treat migraines, osteoarthritis, rheumatoid arthritis, and low back pain. Prednisone (Deltasone) and Decadron (Dexamethasone) are examples of corticosteroids.

Muscle relaxants are used to reduce aches and pains associated with muscle strains, sprains, or spasms by relaxing tight muscles and improving the quality of sleep. Muscle relaxants are not typically recommended for treating chronic pain, but they may help with fibromyalgia and low back pain symptoms. Examples of muscle relaxants include baclofen, tizanidine, chlorzoxazone, methocarbamol, and carisoprodol.

Tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have been shown to be effective for treating chronic pain through their interactions with norepinephrine. SNRIs are the preferred treatment for neuropathic pain as they are generally better tolerated by patients than TCAs. The most commonly utilized SNRI for chronic pain is duloxetine (Cymbalta), which is FDA approved for treating fibromyalgia as well as diabetic neuropathy. SNRIs have a delayed onset of maximal effect and patients may have to wait weeks before achieving best results. Common side effects include diarrhea, nausea, dry mouth, and dizziness.

TCAs remain inexpensive options for treatment of depression as well as for pain control. The dose utilized for pain control is typically lower than the dose utilized

for antidepressant treatment. Commonly utilized TCAs for pain are amitriptyline (Elavil) as well as nortriptyline (Pamelor). Common side effects include dry mouth, dizziness, weight gain, and constipation.

In patients on serotonergic drugs, a rare, but potentially life-threatening condition known as serotonin syndrome can occur when excess serotonin builds up in the body (this can occur if two serotonergic medications are taken concurrently or if an excess of a serotonergic drug is consumed). Symptoms of serotonin syndrome can vary from mild symptoms including diarrhea and nausea to severe symptoms including fever, seizures, and hyperreflexia.

Anti-seizure medications treat chronic neuropathic pain by reducing overactive pain signals from damaged nerves. Examples of anti-seizure medications include pregabalin (Lyrica) and gabapentin (Neurontin). Gabapentin and pregabalin are both FDA approved for postherpetic neuralgia and pregabalin is also FDA approved for diabetic neuropathy and fibromyalgia. Side effects of gabapentin and pregabalin include weight gain, fluid buildup, sleepiness, and drowsiness. Gabapentin and pregabalin cannot be stopped abruptly; they must be withdrawn gradually to minimize withdrawal symptoms such as confusion, delusions, agitation, and sweating.

## **5. Novel pharmacologic approaches to chronic pain**

#### **5.1 Ketamine**

Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist originally labeled as CI-581, is a phencyclidine derivative that has been in clinical use since its FDA approval in 1970 after which it became recognized for its ability to safely induce short-term anesthesia and analgesia. Its use was limited in clinical practice because of its psychodysleptic, hallucinatory, effects. Recently, ketamine has become the subject of research interest and began to be used in acute, chronic, and cancer pain management [19]. Its potential to be a future pharmacologic treatment option for conditions ranging from major depressive disorder and addiction to asthma and cancer growth is also being studied [20].

Ketamine noncompetitively binds to the ligand-gated NMDA receptors in the central nervous system, particularly in the prefrontal cortex and hippocampus, which results in decreased channel opening frequency and duration. Since activation of the NMDA receptor is believed to play a major role in chronic pain, the effect of ketamine on the NMDA receptor in combination with its effects on non-NMDA pathways involved in pain regulation is believed to be responsible for its analgesic properties [21]. Non-NMDA pathways thought to be associated with the analgesic properties of ketamine include the nicotinic and muscarinic cholinergic receptor antagonism, sodium and potassium channel blockade, high-affinity D2 dopamine receptor and L-type voltage-gated calcium channel activation, GABA-A signaling, and descending modulatory pathway enhancement [22].

The increased use of intravenous ketamine infusions for chronic pain treatment in recent decades motivated the development of consensus guidelines in 2016 by the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists [23, 24]. The results of studies on efficacy of ketamine for chronic neuropathic pain and nociceptive pain are promising although results of the nociceptive pain studies are mixed. A metanalysis of 211 patients from

seven studies showed IV ketamine infusions demonstrated analgesia compared to placebo [19, 25]. In this study, the average infusion duration was 5 hours with a median ketamine dose of 0.35 mg/kg, with maximum effect observed between 48 hours and 2 weeks after infusion [25].

Although many pain clinics may administer ketamine intravenously, clinical regimens may encompass either continuous infusion or involve a bolus dose. The most common continuous IV ketamine infusion dose is from 2.0 to 5.0 mcg/kg/min. In some clinics, that continuous infusion dose may be preceded by an IV ketamine bolus of 0.5–1.0 mg/kg [26]. Ketamine infusion time is typically from 30 to 60 minutes in duration for one treatment. In some cases, the infusion duration may be up to 2 hours. The ketamine infusion treatment series generally consists of a total of four to six treatments that are administered two to three times per week, with the number of treatments increased if the patient does not demonstrate adequate response. Adverse effects of ketamine include increased secretions, bronchodilation, hallucinations, visual disturbances, unpleasant dreams, dysphoria, hepatotoxicity, and cystitis. See **Table 4** for a summary of this discussion.

## **5.2 Cannabis/CBD**

Cannabis, also known as hemp, is derived from a genus of flowering plant strains that produce active ingredients such as tetrahydrocannabinol (THC) and cannabidiol (CBD). The mechanism of action of THC comprises activation of cannabinoid receptor type 1 (CB1 receptor) and cannabinoid receptor type 2 (CB2 receptor) [27]. CB1 receptor expression is in the central and peripheral nervous system, while CB2 receptor expression is primarily in the periphery, mostly in cell types involved in immunity, hematopoietic cells, and glia cells [27]. These receptors result in both the analgesic and the psychotropic effects of cannabis [27]. CBD has demonstrated a negative allosteric effect on CB1 receptors and positive modulatory effects on the endocannabinoid system, which results in reduction of psychotropic effects from THC and potentiates the anticonvulsant and analgesic effects when administered concomitantly. Unlike THC, CBD is not psychotropic.

Although plant strains from which cannabis is derived have been grown for at least 12,000 years and there has been evidence of medicine use by Chinese emperors in 2700 BC, cannabis is still considered an investigational drug. Nabilone and dronabinol are synthetic derivatives of THC that are approved by the FDA for treating nausea and vomiting associated with chemotherapy. Clinical trials demonstrate potential for treatment of nausea and vomiting resulting from chemotherapy, appetite stimulation, chronic pain, and muscle spasms [27, 28]. Routes of administration for cannabis and its derivatives include inhalation vias smoking, ingestion, rectal, sublingual, transdermal, ocular, and intravenous [28].

Adverse effects of short-term use of cannabis include impairments in memory, motor coordination, and judgment. At higher doses, cannabis can also result in paranoia and psychosis. Long-term use of use of large quantities of marijuana can lead to addiction, cognitive impairments, chronic bronchitis (if use is via inhalation or smoking), and increased risk of chronic psychotic disorders such as schizophrenia in individuals with a high predisposition [28, 29]. There is also evidence that THC and CBD, the active components of cannabis, act on cytochrome P450 isozymes to influence the metabolism of substances, with THC being an inducer of CYP1A2 and CBD being an inhibitor of CYP3A4 and CYP2D6 [30]. **Table 4** provides a summary of this discussion.

## **5.3 Infusion therapy**

Infusion of IV lidocaine is a modality that can be considered. IV lidocaine is primarily indicated for treatment-resistant peripheral neuropathy [31].

Lidocaine, when used as a local anesthetic, blocks sodium-gated channels, which desensitize peripheral nociceptors. When used as an infusion, IV route, the lower dose blocks the sodium channels of the central nervous system (CNS), mainly affecting the spinal cord and dorsal root ganglia (DRG). Additionally, lidocaine can also affect potassium-gated cannels at the DRG; hyperpolarization cyclic nucleotides channels (HCN); and N-methyl-D-aspartate, (NMDA). The effect on the potassiumgated channels and HCN can contribute to spinal anesthesia. Lidocaine also has anti-inflammatory properties as it decreases cytokines and increases acetylcholine in the CSF, which inhibits spinal pain pathway.

IV lidocaine dosing varies; however, per a recent systematic review, pain clinics have dosed in the following: weight-based of 1–2-mg/kg bolus, a fixed-bolus dose of 50–100 mg, and a 1-mg/kg/hour continuous infusion. Notably, there is also no standard for duration of administration, and serum monitoring is not common practice [32].

Though not an absolute contraindication, careful dosing in patients with cardiac or hepatic failure is essential. The volume of distribution is smaller and the half-life is shorter in the former and the volume of distribution is larger and the half-life is longer in the latter [33]. Other possible complications include headaches, tinnitus, nausea, lightheadedness, paresthesia, hypotension, arrhythmia, respiratory depression, and cardiac arrest [31]. **Table 4** provides a summary of this discussion.


#### **Table 4.**

*Novel pharmacologic approaches to pain management with dosages, benefits, and common side effects.*

## **5.4 Additional treatments**

## *5.4.1 Paravertebral injection of botulinum toxin (Botox)*

Paravertebral injection of the botulinum toxin (Botox), commonly used in the treatment of headaches, appears to also have a place in the treatment of chronic lower back pain [34]. Botox's mechanism of action involves the reduction of muscle hyperactivity and tension by blocking the presynaptic release of acetylcholine [35].

The most common side effects include bruising and pain at the injection site. Dysphagia can be caused by injections near the neck and mouth. Contraindications include infection near injection site, allergy to medication, Eaton Lambert syndrome, or Myasthenia Gravis. Patients must be 13 years or older and not pregnant or nursing. Botox should be used with caution in patients with neuromuscular conduction disease or taking medications that alter this as well as those with peripheral motor neuron disease [35].

## *5.4.2 Trigger point injection*

Trigger point injections or dry needling is typically used for myofascial pain. They also have a role in alleviating pain from post-mastectomy pain syndrome (PMPS) [36]. These points are identified by palpation, observing for tenderness, referred pain or even twitching of muscle fibers when compressed, commonly referred to as "knots." A needle or an injection containing local anesthetic (avoid bupivacaine as this can be myotoxic) or even saline is inserted at these points directly into the muscle tissue. Care must be taken to avoid any major structures [37].

In order to carry out this procedure, a needle is inserted into the trigger point and "fanning" can be done, which theoretically disrupts connective tissue and causes muscle fiber relaxation and lengthening. Recent studies are currently exploring Radial Extracorporeal Shock Wave Therapy as an alternative to trigger point injections in the treatment of myofascial pain [38].

## **6. The use of external stimulation devices for chronic pain**

## **6.1 Transcutaneous electric nerve stimulation (TENS)**

Transcutaneous electrical nerve stimulation (TENS) is a safe, portable, costeffective, and noninvasive treatment approach used for pain management in patients who are refractory to pharmacological intervention. Electrical pulses are delivered to adhesive electrode pads positioned on the patient's skin overlying the region where treatment is to be administered [39]. The duration, frequency, and intensity of the electrical pulses delivered by the device can be adjusted by the care provider. The electrode pads are attached to two or more electrode wires connected to the batterypowered TENS device. TENS is believed to relieve pain via decreasing dorsal horn neuron sensitization and increasing gamma-aminobutyric acid (GABA) and glycine levels. **Figure 1** below shows a common setup for outpatient TENS treatment.

Indications for use include musculoskeletal pain, neuropathic pain, osteoarthritis, fibromyalgia, pelvic pain, and lower back pain [40, 41]. The use of TENS is not recommended in patients who have electronic implants such as pacemakers and cardiac

## **Figure 1.** *A schematic of a common setup for TENS treatment.*

defibrillators. Caution is also advised before use in individuals who are pregnant, have epilepsy, have active malignancy, have blood clots, have damaged skin, and are immunocompromised [42, 43]. Adverse effects of TENS include skin burns where electrode pads are placed and allergic reaction to electrode pad or its adhesive [39].

## **6.2 Inferential current stimulation**

Interferential current stimulation (ICS) is a convenient, cost-effective, and noninvasive treatment approach used for pain management in patients who are refractory to pharmacologic intervention. In ICS, alternation of two or more sinusoidal currents simultaneously generates interference and maximizes the ability of the current to permeate tissues while maintaining minimal cutaneous nerve stimulation [44]. Intersection and interference of currents in the region to be treated are facilitated by the way the two or more electrodes are placed on the skin for ICS treatment. **Figure 2** shows a schematic of outpatient ICS treatment.

Indications for use include muscle stimulation such as for physiotherapy or rehabilitation, knee osteoarthritis, chronic low back pain, shoulder soft tissue pain, chronic jaw pain, fibromyalgia, incontinence, edema reduction, and myofascial syndrome pain [44–46]. The use of ICS is contraindicated in patients who have implanted electronic devices such as pacemakers, cardiac defibrillators, or hearing aids. Caution is advised before use in patients who are pregnant, have cardiovascular disease, have inflammation or fever, have active malignancy, and have thrombosis. Adverse effects include skin burns, bruises, blisters, or swelling of skin overlying treated region as well as discomfort or muscle soreness in the treated region.

## **6.3 Pulsed electromagnetic field therapy**

Pulsed Electromagnetic Field Therapy (PEMF or PEMT) is a safe, noninvasive treatment approach used for pain management in patients who are refractory to pharmacologic intervention.

The PEMT device consists of a mat comprised of spiral coils and frequency generator that energizes the coils to generate a pulsed electromagnetic field [47, 48]. That electromagnetic field in turn induces electric fields in the patient's conductive

*Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

**Figure 2.** *A schematic of a common setup for ICS treatment.*

tissues via inductive coupling. PEMT is believed to cause changes in cellular signaling and modulation of inflammatory cytokines, growth factors, and membrane receptors that produces an analgesic effect [49–51]. **Figure 3** shows a common setup for PEMF/ PEMT treatment.

Indications for use include healing of non-union fractures, stress urinary incontinence, cervical fusion, depression, anxiety, brain cancer, fibromyalgia, rheumatoid arthritis, musculoskeletal pain, knee osteoarthritis, chronic pelvic pain, and chronic low back pain [52, 53]. The use of ICS is contraindicated in patients who have implanted devices such as cardiac defibrillators and pacemakers. Caution

**Figure 3.** *A schematic of a common setup for PEMF treatment.*

is advised before use in patients who are children, are pregnant, have cardiovascular disease, have inflammation or fever, have active malignancy, and have thrombosis. Adverse effects include possible cancer risk from exposure to low-frequency magnetic field.

### **6.4 Diathermy**

Diathermy is a noninvasive treatment approach used for pain management in patients who are refractory to pharmacologic intervention. The technique involves the controlled production of heat within body tissues using high-frequency electromagnetic current generated by diathermies, deep-heating agents such as ultrasound, shortwave, and microwave [54]. The heat generated is believed to increase local circulation, thus promoting toxin removal, facilitating tissue repair, and providing pain relief [55]. **Figure 4** shows a schematic for a common diathermy setup.

Indications for use include rotator cuff disease, bursitis, tendinitis, osteoarthritis, peripheral neuropathy, low back pain, musculoskeletal pain, and fibromyalgia [56, 57]. The use of ICS is contraindicated over wet dressings, reproductive organs, and infected open wounds. It is also contraindicated in patients who are pregnant, have impaired thermal sensation, have implanted devices such as pacemakers, have metal implants, have severe edema, and have bleeding disorders. Caution is advised before use in patients who have cardiac disease, have vascular disease, have active infection or fever, have active malignancy, and have thrombosis. Adverse effects include burns in the treated and adjacent tissues, shock or burn, and excessive heating of metal implants in body such as dental fillings or bone pins.

## **7. Interventional management of subacute and chronic pain**

Interventional pain management, borne of regional anesthesia and neural blockade, has evolved into a multimodal, multidisciplinary approach to treat the incredibly costly and debilitating symptoms of chronic pain. Due to the more

*Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

invasive nature of interventional procedures, they are not usually first line in the treatment of subacute to chronic pain. Typically, patients are seen in the pain management clinic after failure of pharmacological and/or physical therapy for at least 6 weeks. In 2016, low back and neck pain costs an estimated \$134.5 billion dollars and the most common symptom patients present with at interventional pain clinics [58].

Since the 1950s, epidural steroids injections (ESIs) have been used for pain relief of chronic lower back and neck pain, particularly for treatment of radiculopathy. ESI continues to be a mainstay of procedural pain management [59].

Interventional procedure steps may differ and depend on the physician's training and/or patient's body habitus, and the procedures described in this section take that into account in addition to two major pain society guidelines.

#### **7.1 Injectates**

#### *7.1.1 Glucocorticoids*

Long-acting (depot) glucocorticoids can be used in intra-articular and epidural injections. Two of the most used depot glucocorticoids include methylprednisolone acetate and triamcinolone acetonide. For peripheral intra-articular injections, there is no current standard for dosing of these steroids; however, it is common practice to base the dose on the size of the joint. For methylprednisolone acetate, 10–20, 40–60, and 40–80 mg are used in small, medium, and large joint sizes, respectively. Triamcinolone acetonide dosing is 8–10, 20–30, and 20–40 mg on small, medium, and large joint sizes, respectively.

Contraindications for injectates are septic arthritis due to risk of exacerbation of infection, juxta-articular osteoporosis due to risk of worsening bone density, periarticular fracture as glucocorticoids can inhibit bone healing, and join instability due to risk of weakening adjacent ligaments and capsule [60].

#### *7.1.2 Local anesthetics*

The most utilized local anesthetics include lidocaine and bupivacaine, both amides. These anesthetics can be used with or without epinephrine. Epinephrine is added for its vasoconstriction effects that decrease uptake of the local anesthetic into the circulatory system, which affects the cardio-and neuro toxicity and allowing for higher dosages, increases duration of action of the local anesthetic (except for bupivacaine), and decreases bleeding. The addition of epinephrine to local anesthetics is not recommended in procedures on digits of patients with peripheral vascular disease.

In the adult patient, lidocaine without epinephrine dosing should not exceed 4 mg/kg. Lidocaine with epinephrine should not exceed 7 mg/kg. Bupivacaine without epinephrine dosing should not exceed 2 mg/kg meanwhile bupivacaine with epinephrine should not exceed 3 mg/kg. Notably, lidocaine has a higher allowable dose increase with epinephrine when compared to bupivacaine because bupivacaine is more cardiotoxic due to its slower rate of dissociation at diastole, cardiotoxicity being the dose-limiting adverse reaction.

Bupivacaine, typically used at 0.25–0.5% concentration, is longer acting than lidocaine [61]. **Table 5** compares the more commonly used local anesthetics in pain clinics.


#### **Table 5.**

*Comparison of commonly used local anesthetics for interventional pain procedures.*

## **7.2 Imaging**

Interventional pain clinics rely on either surface landmarks or image guidance such as computed tomography (CT), fluoroscopy, or ultrasound. Historically, surface landmarks were the choice among physicians in performing interventional pain procedures. Imaging is more common now for the accuracy and precision of a procedure as well as improved safety of the patient. Ultrasound guidance, the oldest of the aforementioned imaging modalities, had resurgence across multiple specialties including pain medicine as it is a bedside, point-of-care tool that provides real-time visualization of needle placement and advancement as well as adjacent structures. Ultrasound technology also reduces radiation exposure to both patient and interventionalist [62].

An ultrasound suite requires a smaller footprint when compared to a room that has a C-arm (used for fluoroscopic guidance). Room and equipment setups vary according to physician preference. **Figure 5** below shows an example of a common material setup for ultrasound-guided injection within a room.

#### **Figure 5.**

*A schematic of a common setup for ultra-sounded guided procedures (not drawn to scale).*

## **7.3 Joint injections**

Most of the procedures listed below can be done with ultrasound or fluoroscopic guidance.

## *7.3.1 Hip joint injection*

The hip joint is the articulation of the acetabulum and the femoral head, also known as the femoroacetabular joint, is essentially a ball-and-socket joint. Notably, 40% of the femoral head is in contact with the acetabulum, lubricated by synovium, at all times—in extension, flexion, rotation, which allow for steady gait, rising from a seated position and general mobilization. This major joint is stabilized by way of ligaments (ischiofemoral, pubofemoral, and iliofemoral) and cartilage, particularly, the labrum. Osteoarthritis of the hip is deterioration of the articular cartilage, and this wear and tear may cause pain that can significantly affect activities of daily living (ADLs) [63]. This procedure can be done via either ultrasound or fluoroscopic guidance.

For performing the procedure under fluoroscopic guidance, anatomical landmarks are first identified by way of fluoroscopy in the AP and oblique views. The patient's hip region is prepped and draped in sterile fashion. The skin and subcutaneous tissues at the needle entry site are infiltrated with a small amount of Lidocaine. The needle is then advanced incrementally under fluoroscopic guidance toward the point where the femoral head meets the femoral neck until os is contacted and the joint space is entered. After negative aspiration, a small amount of contrast solution is injected showing an appropriate arthrogram to ensure that needle termination is not in an adjacent bursa and thereby truly intra-articular. Then, a solution consisting of a local anesthetic mixed with a glucocorticoid is injected slowly. **Figure 6** is an image of a fluoroscopic-guided right hip injection.

For performing the procedure under ultrasound guidance, the patient's hip region is prepped and draped in the usual sterile fashion. A needle is advanced incrementally under ultrasound guidance toward the femoral neck until os is contacted and the joint space is entered. The local anesthetic and glucocorticoid mixture is given after negative aspiration.

Potential risks and complications include infection, small vessel injury, and bleeding. Contraindications include, but are not limited to, acute fracture, bacteremia, septic arthritis, or infection at needle entry site.

## *7.3.2 Sacroiliac joint injection*

Sacroiliac (SI) joint pain is a common cause of mechanical low back pain. It is a pain, when described by patients, radiates to the back, typically below L5, and groin. Typically, degenerative etiology, pregnancy, or trauma can also cause SI joint pain. SI joint injections can be diagnostic as well as therapeutic. The SI joint, as the name suggests, is located between the sacrum and the ilium, bilaterally. Sensory innervation of this joint is not clearly defined; however, it may be lateral branches from dorsal sacral foramen and possibly L5 dorsal rami as well as the superior gluteal nerve [64].

The procedure is typically done with the guidance of fluoroscopy. The patient is prepped in a prone position until the inferior borders of the SI bony plates are parallel on imaging. With intermittent fluoroscopy, needle inserted is inferior until popping sensation is appreciated. Contrast is injected and should outline the SI joint. As with other joint Injections, injectate is local anesthetic and corticosteroid. This can also be done under CT or ultrasound guidance [65]. **Figure 7** shows an image of a right SI joint injection under fluoroscopy.

The risks to this procedure include increased pain at the site of insertion or injection, infection, trauma to nearby anatomy, including nerves. Unsuccessful pain reduction is also possible, when done under fluoroscopic guidance, this appears to be around 10% risk of failure [66].

#### **Figure 7.**

*An example of an image captured during fluoroscopic-guided right SI joint injection performed in the interventional pain clinic.*

## **7.4 Neuronal blockade**

Different forms of neural blockade, initially used for surgical anesthesia, have secured their positions in chronic pain management.

## *7.4.1 Greater occipital nerve*

The greater occipital nerve (GON) block can be used as a primary treatment for multiple types of severe headaches or, more commonly, treatment-resistant headaches. A GON block can relieve migraines, cervicogenic headaches, post-dural puncture headaches, and even optic neuralgia. GON block is particularly useful for patients who are not able to tolerate more common pharmacologic regimens, such as those with multiple comorbidities, as well as the elderly and pregnant patient population [67]. The GON stems from the medial branches of dorsal primary rami of the cervical nerve roots C2 – C4, and occasionally C5 and innervates the posterior scalp [68].

To carry out the procedure, the patient is placed in a prone or seated position with slight flexion at neck. Identify the surface landmarks, typically palpated, mastoid process, and occipital protuberance ipsilateral to the headache pain. The GON is about two-thirds of the distance from the mastoid process to the occipital protuberance, about 2 cm lateral and 2 cm inferior from the protuberance. Insert needle from an infero-lateral approach until contact is made with the periosteum and then retract about 1 mm. Aspirate needle at this location to ensure that needle tip is not in the occipital artery and inject with or without a sweeping motion. This can be done with ultrasound guidance and should be noted that GON is typically medial to the occipital artery as shown in **Figure 8**.

Local anesthetic with or without glucocorticoid is commonly used as the injectate. The use of glucocorticoids can be specifically effective for certain types of headaches such as cluster headaches [69].

As with other nerve blocks, intravascular injection can lead to significant complications. Cushingoid, secondary to excess glucocorticoid, can occur with serial blocks that contain glucocorticoid treatment [70].

## *7.4.2 Celiac plexus*

The blockade of the celiac plexus can be used for intractable abdominal pain, and most commonly pain caused pancreatic cancer [71, 72]. The celiac plexus has three major components, celiac, aortic, and superior mesenteric stemming from the anterolateral horn of the spinal cord at T5–T12. The celiac plexus innervates the gallbladder, liver, pancreas, and gastrointestinal tract from the stomach to the transverse colon [73].

To carry out this procedure, the patient is positioned in prone and with maximal kyphosis by bolster. Recent evidence suggests that ultrasound-guided celiac plexus blocks are safer and less costly [74]. The surface landmarks are T12 and L1 vertebral bodies. The needle is inserted at the inferior border of the 12th rib, about 6–8 cm from the midline, at a 45-degree posterior to anterior angle, and advanced toward the ventral surface of T12-L1 intervertebral space. Once contact is made with vertebral body, needle is advanced further by 1 cm into the prevertebral fascial plane. This can be confirmed by fluoroscopy [73]. **Figure 9** shows the anatomic considerations for the celiac plexus at vertebral level T12.

If a patient is unable to lie prone, an anterior para-aortic approach can be useful. At the anterior T12 vertebral body, the needle is inserted and advanced toward the abdominal aorta and injected into the antero-crural space. It must be noted that an anterior approach has a higher risk of organ injury [73]. In terms of the injectate used,

**Figure 9.** *Anatomic considerations for the celiac plexus.*

#### *Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

steroid and local anesthetics are used for benign etiologies of pain and neurolytics are for malignant etiology.

The possible complications from a celiac plexus nerve block or neurolysis include but are not limited to the following: orthostatic hypotension, paresthesia, infection, pneumothorax, paraplegia, and a higher risk of organ damage with the anterior approach [75].

## *7.4.3 Superior hypogastric plexus*

The blockade of the superior hypogastric plexus can be used for chronic pelvic pain caused by multiple etiologies including endometriosis, inflammatory processes, postoperative adhesions, and malignancy [76]. The superior hypogastric plexus is located in the retroperitoneal space, between L5-S1 vertebral bodies.

In the posterior approach, the patient is placed in prone position with emphasized flexion at the lumbar spine by bolster. The surface landmark of L4-L5 intervertebral space is identified, and under fluoroscopic-guidance, the needle is inserted 5–7 cm lateral of the middle of this space, from either side, at a 30-degree oblique and 30-degree caudad angle, toward the anterolateral L5-S1 paraspinous junction. Contrast should spread midline in the AP view and needle tip should be visualized at the anterolateral margin of L5 and spread anterior to the L5 vertebral body. It is important to emphasize the proximity of the superior hypogastric plexus to the iliac vessels [77]. Local anesthetic or neurolytic is commonly used as injectate.

This procedure can cause transient or even permanent retrograde ejaculation as the urogenital system is primarily innervated by the superior hypogastric plexus.

#### *7.4.4 Medial branch block (MBB) injection*

Facet joint injection is the injection of a combination of steroid and local anesthetic at the site of the joint, while medial branch block is injected right outside the joint at the medial branch of the dorsal rami. Theoretically, either may have prognostic value for radiofrequency ablation and the latter with more therapeutic value, however, mostly short-term. Common practice at pain management clinics usually requires successful diagnostic medial branch blocks on two separate occasions, which can be followed with radiofrequency ablation [78]. MBBs are indicated for spondylosis, post-laminectomy syndrome, facet arthropathy, and disk degeneration.

To carry out this procedure, the patient is placed in the prone (lumbar) or supine (cervical, anterior approach, other approaches include posterior or posterolateral, dependent on technique of interventionalist) position. Anatomical landmarks are identified with the aid of fluoroscopy in the PA and oblique views [77].

For the Lumbar Spine: The patient's lumbar region is prepped and draped in sterile fashion. The skin and subcutaneous tissues at each needle entry site are infiltrated with a small amount of lidocaine using a needle is incrementally advanced under fluoroscopic guidance in multiple views at each level such that the needle tip is advanced to contact os at the junction of the superior articulating process and the superomedial border of the transverse process at each of the cephalad levels as well as to contact os at the junction of the superior articulating process and the superomedial border of the sacral ala at the S1 level. After negative aspiration is confirmed, a small amount of lidocaine is injected into the cephalad needles and a small amount of 0.25% Bupivacaine is injected at the S1 level.

For the Cervical Spine: The patient's cervical region is prepped and draped in sterile fashion. The skin and subcutaneous tissues at each needle entry site are infiltrated with approximately a total of 3 mL of 1% lidocaine. Needles are advanced under fluoroscopic guidance from the lateral view such that the needle tips are positioned on os at the center of the cuboid masses of the posterior columns of targeted levels. Needle placement should be confirmed via fluoroscopy. At each level, following negative aspiration, a small amount of 0.25% Bupivacaine (or other anesthetic) is injected slowly.

After the procedure, the patient's skin is wiped clean and bandages are placed. **Figure 10** shows an example of an image capture by fluoroscopy for a medial branch block while **Figure 11** is an illustration that shows approximate location of the medial branch in relation to a vertebral body and facet joint.

In terms of anatomic considerations, the C3 deep medial branch, C4, and C6 medial branches are located slightly above the waist of their corresponding articular pillars and C5 medial branch tends to be located right at the waist of the articular pillar. The risks of the procedure include trauma or damage to nearby structures including the spinal cord or adjacent nerves, infection, epidural bleeding, or hematoma.

Other neuronal blocks include stellate ganglion as shown in **Figure 12** for head, neck, and upper arm pain, and genicular nerve for chronic osteoarthritis of the knee as shown in **Figure 13**.

Other procedures include shoulder injections as shown in **Figure 14** and piriformis injection as shown in **Figure 15** for piriformis syndrome, most commonly causing sciatic nerve entrapment and subsequent symptoms. Bursa injections provide relief for bursitis particularly trochanteric, ischial, subacromial, olecranon, and prepatellar.

#### **Figure 10.**

*An example of an image captured during fluoroscopic-guided medial branch block performed in the interventional pain clinic.*

*Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

**Figure 11.** *Anatomical considerations for medial branch blocks.*

**Figure 12.** *Anatomical considerations for stellate ganglion blockade.*

## **7.5 Radiofrequency ablation**

Literature on radiofrequency ablation (RFA) continues to show mixed results on its cost effectiveness and therapeutic efficacy [79]; despite this, RFA continues to be commonly performed in interventional pain suites, most commonly for facet joint pain as well as SI joint pain.

**Figure 13.** *Anatomical considerations for genicular nerve blockade.*

Prior to first time ablation of the MBB for facet joint pain, at least two rounds of successful diagnostic MBBs are usually required. Some hospital systems, such as St. Luke's University Health Network (SLUHN), provide patients with a pain diary after MBB to gauge success of procedure prior to RFA. Repeat ablation may have different prerequisites in different locations. Patients are educated that the goal of RFA is a 50% reduction in pain for about 6–12 months since tempering patient expectations is a mainstay of pain management practice.

RFA is currently being used for facet joint pain by targeting the medial branch of the dorsal ramus (since reimbursement is trending away from intra-articular facet joint injections), discogenic pain (ramus communicans), SI joint pain as well as radicular pain (DRG).

To carry out RFA, the patient is placed in the prone position. Anatomical landmarks are identified by way of palpation with fluoroscopy in the PA and oblique views. The patient's lumbar region is prepped and draped in the usual sterile fashion using chlorohexidine. The skin and subcutaneous tissues are infiltrated with a small amount of 1% Lidocaine at each of the intended needle entry sites. Via fluoroscopy in the AP and oblique views, needle tip is incrementally advanced under fluoroscopic guidance at each level. At each of these levels, the needle tip contacts the os at the superior medial border of the junction of the transverse process of the lumbar levels and to contact the os at the medial aspect of the groove formed by the sacral ala in the superior articular process of S1.

After proper needle placement is confirmed with fluoroscopic guidance at each level, sensory and/or motor stimulation is performed at 2 Hz and 50 Hz, respectively. Small amount of 2% lidocaine is instilled at all levels. After a period of approximately 90 seconds, each level is lesioned at 90 degrees Celsius. Following the initial lesioning,

**Figure 14.** *Anatomical considerations for shoulder injections.*

**Figure 15.** *Anatomical considerations piriformis injection.*

each needle tip is repositioned x 2 under fluoroscopic guidance in a clockwise and counterclockwise fashion. Following each reposition, a total of two additional lesions at each side are performed for 90 seconds at 90 degrees Celsius. See **Figure 16** for common settings. After all needles are removed, skin is wiped clean and bandage is placed [77]. **Figure 17** is a schematic of a common room setup for an RFA procedure.

**Figure 16.** *Initial RFA settings are 90° C for 90 seconds.*

**Figure 17.** *A schematic of a common setup of an RFA room (not drawn to scale).*

Classically, RFA involves thermal energy to cause a lesion and subsequent disruption of a nociceptive pain pathway, by way of Wallerian degeneration. There are currently other iterations including water-cooled radiofrequency ablation (WCRF), cryo-neurolysis, and pulsed radiofrequency ablation [80].

Dizziness and ataxia are possible complications, particularly with cervical RFA. There is also the possibility of infection, cutaneous numbness, dysesthesia, postprocedural pain, and trauma to adjacent structures.

The above discusses conventional continuous radiofrequency ablation. There is also pulsed radiofrequency ablation (PRF) that delivers sort bursts of current and water-cooled radiofrequency ablation (WCRF), a method that uses a continuous flow of water to regulate the flow of current and prevents the needle from overheating.

## **7.6 Spinal cord stimulation**

Spinal cord stimulators (SCS) are indicated for persistent pain status post spinal surgery also known as failed back surgery syndrome (FBSS), and it is moderately effective for radicular pain. It can also be used for Complex Regional pain syndrome (CRPS), painful diabetic neuropathy, and even postherpetic neuralgia and axial low-back pain. Notably, in Europe, SCS is used in refractory angina and peripheral vascular disease [81]. Psychiatric evaluation clearance is common place practice prior to a SCS trial. SCS is typically done in two stages, including a trial device and if effective (50% reduction in pain [82]) final device placement, both done under fluoroscopy.

A SCS trial includes the following steps: The patient is placed in the prone position with legs, abdomen, and arms padded, neck should be noted in neutral position with minimal discomfort. Patient is prepped in sterile fashion. Anatomical landmarks are identified by way of palpation and fluoroscopy in the AP view and the skin overlying the initial intended insertion site is infiltrated with a small amount of 1% Lidocaine. A Touhy needle is incrementally advanced using a loss-of-resistance technique with the aid of fluoroscopy in both the AP and lateral views into the appropriate epidural space. An 8-contact lead is subsequently passed through the Touhy needle and advanced into the epidural space under the aid of fluoroscopy to where the tip of the lead was is at the targeted endplate. The lead is confirmed posterior by way of fluoroscopy in the lateral view and in the AP view [77].

The patient's pain is adequately captured with initial stimulation and the introducer needles are removed with tips in place. The electrodes are secured with adhesive strips. Impedance is checked and multiple electric combinations were utilized to provide coverage of the patients' area of pain. **Figure 18** shows an example of a fluoroscopic image of a trial spinal cord stimulator placed in the thoracic spine.

Of note, prophylactic and postsurgical broad-spectrum antibiotics are used at SLUHN for the placement of the trial device.

If the SCS trial is successful, the final device is placed where an incision is made for tunneling the cables leads and a second incision is made to place the pulse generator above the iliac crest after which the lead cables are connected by tunneling to the pulse generator.

General lead placement locations are navigated by the location of pain [83]. **Table 6** below shows suggested lead placement based on symptomatic location of pain.

One of the most common complications of SCS is lead migration or damage causing decreased efficacy of treatment [84]. A more rare but potentially catastrophic

## **Figure 18.**

*An example of an image captured during fluoroscopic-guided thoracic epidural spinal cord stimulator leads trial.*


## **Table 6.**

*Location of pain and associated lead placement for spinal cord stimulation.*

complication is a spinal epidural hematoma, which can occur days to weeks after completion of procedure. Spinal epidural hematoma is a medical emergency and should be considered if patient experiences new onset severe back pain and/or neurological impairment [85]. Other complications include spinal cord trauma and tolerance to treatment, particularly in long-term use [86].

The progressing advancement of SCS has allowed for broadening of indications and will likely continue to do so. Placement of the device after a successful trial is usually completed by a Neurosurgeon or Orthopedic Spine surgeon who specializes in this placement, which can lead to a bottleneck in demand for the device placement. **Table 7** provides a summary of this discussion.


**Table 7.**

*Common indications and complications of Spinal Cord Stimulators indications.*

## **8. Discussion**

The primary goal of the outpatient pain clinic is to help patients improve their quality of life by reducing pain, decreasing dependence on narcotic pain medications, and supporting increased activity levels, thereby allowing a return to a sense of function. Pain may be complex, vague, and wildly subjective, but it can be targeted with a systematic approach that is consistently applied for every patient that presents to the clinic. A thorough history and physical should precede a decision on treatment approach.

The initial evaluation begins with a history of present illness (HPI) and a review of medical history. There are several "red flags" that may significantly alter the treatment plan and warrant further workup; therefore, a thorough history is essential to determine the appropriate treatment approach. When evaluating pain, it is important to take note of location, radiation of pain, duration, quality, severity, exacerbating factors, alleviating factors, history of trauma to the area, as well as the impact this pain has on activities of daily living (ADL). It is also important to note what treatments have already been trialed, including pain medications, external stimulation devices, and surgeries. Pain procedures and alternatives methods are helpful for patients who are not appropriate for more invasive surgical treatment, or for those whom surgery has failed, such as spinal cord stimulators for Failed Back Surgery Syndrome.

The physical exam begins the moment the patient steps foot into the office. General inspection includes overall gait, posture, range of motion, effort, even work of breathing. A neurological exam includes deep tendon reflexes, dermatome and myotome distributions, as well as strength (which can be indicative of neurological and/or musculoskeletal impairment), and tenderness on palpation. Provocation tests are helpful in discerning between symptoms that correlate with more than one etiology and a cluster of positive provocative tests increases accuracy of a diagnosis. For example, if a patient presents with neck pain, a Spurling's test is sensitive but not specific for acute radiculopathy if pain radiates into ipsilateral arm and Lhermitte is specific but not sensitive for cervical spinal cord compression.

Typically, interventional procedures are considered only after a patient has not improved or has experienced only limited improvement on more conservative measures such as medications and/or physical therapy for about 6 weeks. Those whose pain impedes on their ability to participate in physical therapy may also benefit from interventional procedures. Different prerequisites depend on the proposed treatment, and they are illustrated in the charts below (**Figures 14**–**18**). It can be argued that some procedures, especially less invasive procedures such as ultrasound-guided large joint injections, may be appropriate before this timeframe if the goal is to prevent dependence on narcotics, polypharmacy, or the multitude adverse effects pain medications can have.

Since back pain is the most commonly presenting chief complaint in an outpatient pain clinic, it is important to differentiate between organic and nonorganic back pain etiologies. Nonorganic back pain is more suspected if three or more of the following symptoms are positive: pain with axial compression or passive rotation, negative straight-leg raise with patient distraction, regional disturbance that does not follow dermatomal distributions, overreactions to physical examination, and non-anatomic specific tenderness. This does not mean this patient is not feeling pain; however, it may mean that certain procedures are not indicated. Avoidance of more invasive procedures would be prudent if organic back pain is ruled out. Patient with nonorganic back pain may benefit from optimization of medical and mental health, perhaps further workup, or appropriate referrals in addition to other treatments such as aforementioned external stimulation devices for distraction therapy, trigger point injections and/or SNRIs for conditions such as fibromyalgia, or even cannabis/CBD.

When a patient's back pain is suspicious for organic causes, it is helpful to keep broad stroke interventional mainstays in mind. Classically, radicular symptoms, spinal stenosis, and discogenic pain improve with ESI, facet joint dysfunction responds well to MBB, and SI joint dysfunction with SI joint injections. Newer interventions include RFA after a certain number of successful MBBs as well as the ablation of SI joint nerve, SCS for FBSS, and even radicular pain may be appropriate. Pain Management Physicians may wait at least 12 months after surgery prior to considering a trial of SCS for FBSS as it may take this long to recover from spinal surgery. External stimulation devices can be used in patients who cannot or will not undergo more invasive procedures. The chart seen in **Figure 19** is a general guide on how an interventionalist can organize the initial presenting symptoms with a potential treatment.

Research regarding number of ESIs prior to indications of surgical intervention is limited. For some interventional pain medicine physicians, surgery may be considered if subsequent ESIs continue to provide waning or minimal levels of relief either by percent of relief or temporal measures. There are multiple reasons why a patient may never be an appropriate candidate for surgery independent of ESI count.

Navigating the course of action, prerequisites and expectations of different treatments can be daunting for both patient and referring physician. The diagrams below illustrate example steps of some of the major interventional pain procedures, from the moment a patient walks into the clinic until day of procedure. The steps to a diagnostic MBB can be seen in **Figure 20** while the prerequisites for radiofrequency ablation of the Medial Branch can be seen in **Figure 21** as well as its continued use for treatment. **Figure 22** shows the process prior to an epidural steroid injection and in **Figure 23** the steps prior to SI joint injection. These may differ in different practices and can change as literature and policies are updated. It should be noted that the initial treatment is sometimes also known as diagnostic since a failure in that treatment may warrant further workup for source of pain.

## *Outpatient Management of Chronic Pain DOI: http://dx.doi.org/10.5772/intechopen.108993*

#### **Figure 19.**

*An example of a common pathway for epidural steroid injection and SI joint injection.*

#### **Figure 20.**

*An example of a common pathway including requirements prior to a diagnostic MBB.*

The benefits pain management contributes to medicine are vast and the potential contributions are boundless. This chapter pays tribute to the foundations of this specialty while highlighting newer innovations and expanding on already-established

#### **Figure 21.**

*An example of a common pathway including requirements prior to initial RFA of the MBB and continuation treatment.*

#### **Figure 22.**

*An example of a common pathway including requirements prior to diagnostic ESI.*

modalities that may be safer, faster, and more accessible such as ultrasound-guided procedures or advancement of current technology.

In 2019, COVID-19, a disease caused by the virus SARS-Cov-2, quickly spread resulting in a global pandemic and subsequent lockdown. The organic effects of this disease as well as the mental health consequences may have an interesting effect on the patient population presenting to outpatient pain clinics. The importance of a

#### **Figure 23.**

*An example of a common pathway including requirements prior to diagnostic SI joint injection.*

targeted evaluation as well as continued advancement of safer more efficacious treatments, invasive and noninvasive, will likely be more important than ever.

This chapter review is not comprehensive as there is a less detailed focus on already-established procedures such as epidural steroid injections and the multitude of peripheral nerve blocks, which are arguably the pillars of interventional pain management. Instead, this chapter focuses on the innovations that are becoming more common in clinical practice. Since pain management is a robust and advancing field, this chapter may not include newer procedures or lesser studied ones.

There are multiple procedures that have grown out of favor from common practice including discograms as they are painful, facet joint injections as medial branch block, and subsequent ablation provides longer relief for this type of back pain, neurolysis due to its increased risks when compared to neural blockade and ablation, and even intrathecal pumps, which are a good treatment option but require long-term maintenance and troubleshooting.

In contrast, there are forms of therapy such as prolotherapy, which is essentially the repeated injection of irritant or platelet-rich plasma (PRP) injections, which is the injection of autologous platelets into affected joint space to trigger connective tissue growth and/or repair and subsequent theoretical pain relief that are awaiting larger, more in-depth studies prior to acceptance into common practice.

Pain medicine's core specialties include Anesthesiology, Psychiatry, Physical Medicine and Rehabilitation, and Neurology. The diversity of the specialty allows for a multifaceted projection of innovation such as aforementioned prolotherapy and PRP injection as well as the augmentation of the perception of pain and visualizing biomarkers of pain, which expands the scope and impact of outpatient pain management.

## **9. Conclusions**

This chapter briefly describes the mechanism and pathways contributing to the perception of pain before discussing the current pharmacologic and non-pharmacologic agents that modulate these pathways as well as interventional pain approaches that are becoming more commonly used. In the outpatient pain management clinic, the focus is on subacute to chronic, non-cancer pain—its etiologies, evaluation, and subsequent management including the wide array of noninvasive treatments such as ketamine, external stimulation devices, and CBD, as well as more invasive modalities of treatment. We review the mainstay of interventional pain procedures and highlight its innovations such as radiofrequency ablation and spinal cord stimulators. As more research is conducted and technology advances, it is imperative to update medical health professionals on how to better help patients improve their quality of life and regain their function.

## **Acknowledgements**

Sanjay V. Menghani's training is supported by an F30 Ruth L. Kirschstein individual predoctoral NRSA fellowship from the NIGMS (5F30GM139246-02).

## **Conflict of interest**

The authors declare that the work for this book chapter was conducted in the absence of any commercial or financial relationships that could be considered a conflict of interest.

## **Author details**

Franzes Anne Z. Liongson1 \*, Rina Bhalodi1 , Christopher McCarthy1 , Sanjay V. Menghani2,3 and Ajaz Siddiqui4

1 St. Luke's University Hospital Network (SLUHN), Bethlehem, USA

2 University of Arizona College of Medicine – Tucson, Tucson, USA

3 Medical Scientist Training MD-PhD Program, University of Arizona College of Medicine – Tucson, Tucson, USA

4 Spine and Pain Associates, St. Luke's University Hospital Network (SLUHN), Bethlehem, USA

\*Address all correspondence to: franzes.liongson@sluhn.org

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## **Chapter 10**

## Acute Post-Operative Pain Management

*Samina Khatib, Syed S.N. Razvi, Mudassir M. Shaikh and Mohammad Moizuddin Khan*

## **Abstract**

Despite major advances in the field of anesthesia and medicine, postoperative pain continues to be undermanaged in a significant proportion of patients. The consequences of undermanaged pain are deleterious for both patients and the healthcare system. This review aims to give the readers a practical and updated approach to acute postoperative pain management. This chapter deals with the definition of pain, the physiology and pathophysiology of pain, and various approaches to the management of acute pain. A review of the literature was done to understand the methods of pain management with a major focus on the literature of the last decade (2010–2022). A literature search was done on PubMed and Google Scholar using keywords "acute postoperative pain" and "pain physiology." The research papers on the basics of pain physiology, the prevalence of acute post-operative pain and methods of acute postoperative pain management were reviewed. A brief practical approach for acute postoperative pain using pharmacological and non-pharmacological approaches and a brief discussion have been done on the approach for special group of patients. The management of acute postoperative pain can be done using various pharmacological and non-pharmacological methods. The approach for each patient has to be tailored depending on the individual patient's needs.

**Keywords:** acute postoperative pain, nociception, opioids, opioids, pain management, anesthesia

## **1. Introduction**

Anesthesia as a specialty has primarily originated from the human endeavor to control pain. In the evolution of medicine and surgery, complex surgeries have been made possible due to the pain relief given by the science of anesthesia. As modern anesthesiology evolved, the role of anesthesiologists is not confined only to operating and recovery rooms but extends to surgical wards also. Pain management in the postoperative period is one of the most essential components of postsurgical care.

## **1.1 What is pain?**

The International Association for Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage" [1]. Pain is a multidimensional experience with the following components: objective, subjective, physiological, emotional, and psychological [1]. Differences in pain experience are influenced by the biological response, psychological state, personality traits, and social traits [2]. A large systemic review of literature pooled from 165 studies showed that in the first 24 hours after major surgery (abdominal, thoracic, orthopedic, and gynecological), the mean incidence of moderate to severe pain was 30% and 11%, respectively [3]. The incidence of these pain levels varied by analgesic technique, with lower incidence with patient-controlled analgesia and epidural analgesia. A questionnaire survey of Asian countries by Vijayan et al. showed that only 30% of patients in India receive adequate pain management [4]. These and a large number of other surveys and studies show an unacceptable level of acute postoperative pain [5–11].

## **1.2 Pain can also be classified as physiological pain or pathological pain**

Physiological pain is a "normal" sensation and includes a range of transient sensations we experience in response to stimuli that are of sufficient intensity to threaten to damage the tissue or produce small localized areas of injury, but which neither provoke an extensive inflammatory response nor damage the nervous system. Pathological pain is a sensation that arises as a consequence of either the inflammatory response that accompanies tissue injury or as a result of damage to the nervous system [12]. Pathological pain involves the disruption of the normal selectivity or specialization of the somatosensory system [12].

## **1.3 Physiological pain**

The term "nociception" is a process by which information about tissue damage is conveyed to the central nervous system. Nociceptors are specialized, free, unmyelinated nerve endings that convey a variety of stimuli into nerve endings that the brain interprets as pain. Many patients can experience pain in the absence of a noxious stimulus.

The process of pain transmission is illustrated in the **Figure 1** and involves four steps [12]:


## **1.4 Pain pathways and neurobiology of nociception**

The etiology of acute postoperative pain is multifactorial. Surgical tissue injury releases histamine and inflammatory mediators (bradykinin, prostaglandins, serotonin, and nerve growth factor), which in turn activate peripheral nociceptors. These

nociceptors transmit the nociceptive information to the central nervous system by transduction and transmission [12].

Noxious stimuli are transduced by peripheral nociceptors and transmitted by A-delta and C nerve fibers to the dorsal horn of the spinal cord, where integration of peripheral nociceptive and descending modulatory input (i.e., serotonin, norepinephrine, GABA, enkephalin) occurs. After complex modulation, this information is passed on through the spinothalamic tract and spinoreticular tracts to higher centers where the pain is perceived. Some inputs pass to ventral and ventrolateral horns to initiate segmental spinal reflexes, which are associated with increased skeletal muscle tone, inhibition of phrenic nerve function, or decreased gastointestinal motility. The constant release of inflammatory mediators in the periphery sensitizes functional nociceptors and activates dormant ones (enlisted in **Table 1**). Further, it leads to a decreased threshold for activation and an increased rate of discharges. The surgical injury besides causing sensitization of primary and central pathways also leads to feelings of fear, anxiety, and frustration [2]. Intense noxious input from the periphery may lead to central sensitization and hyperexcitability causing a persistent post-injury change in central nervous system in addition to functional changes in the dorsal horn (spinal sensitization). This may lead to acute pain progression to chronic pain [12].The International Association for the Study of Pain defines chronic pain as persistent or recurrent pain lasting longer than 3 months [12].

The systemic response to surgery may contribute to perioperative morbidity and mortality. There are several systemic responses to surgery, including sympathetic nervous system activation, the neuroendocrine stress response, and inflammatory immunologic changes. Commonly observed pathophysiologic changes [14, 15] include:



#### **Table 1.**

*List of cytokines/inflammatory mediators that contribute to acute effects of postoperative pain.*


The neurohumoral responses (peripheral sensitization) and central sensitization have already been explained in the physiology of pain.

Following extensive tissue injury (following surgery), nociceptive impulses stimulate sympathetic cells in the hypothalamus and preganglionic neurons in the anterior lateral horn. Surgical trauma results in increased plasma concentrations of epinephrine and norepinephrine. The magnitude and duration of catecholamine release are directly related to patient factors such as the type of surgery, inherent sympathetic response, patient age, and genetic polymorphisms. Pathophysiological changes associated with increased sympathetic tone and altered regional perfusion are illustrated in **Figure 2** [15].


#### **Figure 2.**

*Pathophysiology of postoperative pain [15].*


## **1.5 Neuroendocrine responses**

Following tissue injury (the nociceptive impulses reach via the spinal cord and midbrain reticular formation), the neurogenic stimuli affect the hypothalamus, secretory target organs, or both and cause a neuroendocrine response [15, 16]. This is also called the stress response to injury and is characterized by increased secretion of catabolic hormones such as cortisol, glucagon, growth hormone, and catecholamines and a decreased release of anabolic hormones such as insulin and testosterone. This results in substrate mobilization, followed by hyperglycemia and a negative nitrogen balance. Associated changes include gluconeogenesis, glycogenolysis, proteolysis, and breakdown of lipid stores. These changes have short-term benefits of enhanced energy production; however, if this response is amplified or prolonged, catabolic aspects of stress response ensue, which can have a negative impact on the postsurgical outcome. The effects may be the following:


release of IL-6 and IL-1 β can also increase ACTH and cortisol secretion. The relation between plasma IL-6 and cortisol levels is linear in postsurgical patients. The prolonged nitrogen balance and sustained secretion of glucocorticoids result in impaired wound healing, decreased immunity, and diminution in protein synthesis, which may inhibit cell division, production of collagen, and acute convalescence; in already debilitated individuals, this can cause postoperative infections.


## **2. Preemptive analgesia and enhanced recovery after surgery**

Surgery produces a biphasic insult on the human body. First of all, during surgery, there is trauma to the tissue followed by an inflammatory process at the site, which is also responsible for noxious input. Both these processes sensitize the pain pathways. They occur at a peripheral level where there is a reduction in the threshold of nociceptive afferents at a central level with increased excitation of spinal neurons involved in pain transmission. This concept has implications in acute postoperative pain management and has led to the concept of preemptive analgesia [18]. This concept states that **t**he analgesic intervention preceding surgical injury is more effective in relieving acute postoperative pain than the same treatment following surgery. It works by preventing central sensitization in central nervous system to intense noxious stimuli, thus preventing pain hypersensitivity and hyperexcitability [18].

Enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care plans intended to accelerate the recovery process after surgical procedures by maintaining preoperative organ function and reducing the intense stress response following surgery [19]. Initiated by Professor Henrik Kehlet in the 1990s, ERAS, enhanced recovery programs (ERPs) or "fast-track" programs have become an important focus of perioperative management. These programs are designed to curtail the physiological and psychological responses to major surgery leading to a reduction in postoperative complications and hospital stays, improvements in cardiopulmonary function, earlier restoration of bowel activity, and earlier recommencement of normal activities. The ERAS protocols help to improve the quality of perioperative care with aim of alleviating the loss of functional capacity and speeding up the recovery process [20].

For ERAS programs, optimal pain management plays a key role. The complex nature of nociception and mixed mechanisms of generating surgical pain is responsible for the failure of unimodal analgesia to adequately address postoperative pain, hence the need for multimodal analgesia. Multimodal analgesia includes using multiple strategies and analgesics acting at various points of the pain pathway to manage postoperative pain. These strategies include patient education; local anesthetics-based infiltration, peripheral nerve blocks, neuraxial analgesia, and a combination of analgesic drugs that act via different mechanisms on different receptors within the pain transmission pathway to provide synergistic effects, superior analgesia, and physiological benefits [11]. The multimodal, evidence-based, and procedure-specific analgesic regimens should be the standard of care to achieve optimal analgesia with minimal side effects and facilitate the achievement of important ERAS milestones such as early mobilization and oral feeding [20]. Thoracic epidural analgesia (T6–T11) remains the gold standard for postoperative pain control in patients undergoing open abdominal surgery. Initiation of neural blockade before surgery and its maintenance throughout the surgery decreases the need for anesthetic agents, opioids, and muscle relaxants [20]. Epidural analgesia provides better postoperative static as well as dynamic analgesia for the first 72 hours to accelerate the recovery of gastrointestinal functions, decrease insulin resistance, and impact positively cardiovascular and respiratory functions. Intra-thecal analgesia is a valuable analgesic technique to improve early postoperative analgesia and facilitate surgical recovery [20]. Opioid side effects are dose-dependent and can cause a delayed recovery. Opioid-sparing analgesic strategies such as regional anesthetic techniques should be implemented in a context of a multimodal analgesic regimen.

Continuous wound infusion of local anesthetics leads to improved postoperative analgesia and reduces opioid consumption; however, the effect on the recovery of

bowel function is unclear. The use of intravenous lidocaine infusion, abdominal truncal blocks, intra-peritoneal anesthetic, and multimodal approach using NSAID, COX2 inhibitors, and paracetamol decreases opioid consumption by 30% and dosedependent side effects [20].

In ERAS, the attenuation and treatment of postoperative ileus are also important [20]. The prolonged ileus can be prevented by the use of opioid-sparing strategies, thoracic epidural analgesia, intravenous lidocaine, NSAIDs/COX-2inhibitors, ketamine, etc. The use of opioid antagonists such as alvimopan and metitrexone, the use of laxatives, and gum-chewing are useful strategies to reduce side effects related to opioids [20].

## **3. Assessment of pain**

This step is vital for effective pain management. Pain assessment should be done during rest as well as during movement. The assessment should be done before and after every treatment to evaluate the effectiveness of the treatment. In conditions where the pain is intense or in the intensive care units, and surgical wards, pain assessment, treatment, and re-evaluation should be done frequently or at regular intervals. Documentation of pain and response to treatment and adverse effects on a vital sign sheet is very much essential for proper treatment. It facilitates proper communication between staff and also facilitates auditing and quality control. Special attention should be paid to patients who cannot communicate their pain, e.g., those who are cognitively impaired, pediatric patients, unconscious patients, etc.

## **3.1 Self-assessment tools**

Patient self-report is the most useful tool and the gold standard, and one should always listen to the patients and believe what they say. Several patient self-assessment tools are available:


The VRS and NRS are used most frequently while VAS is used mainly as a research tool.

Postoperative pain control is often not isolated to the surgical site but includes other locations such as sore throat following intubation and also injection sites [21]. One approach is preparing a body map and marking the sites with pain and individual

## *Acute Post-Operative Pain Management DOI: http://dx.doi.org/10.5772/intechopen.109093*


#### **Figure 3.**

*Behaviorial pain scale [24].*

pain scores, but this is a tedious and impractical approach for the postoperative period. The multidimensional tools are under validation such as the Clinically Aligned Pain Assessment (CAPA) tool that measures five dimensions of pain including comfort, change in pain, pain control, functioning, and sleep [22]. It may improve assessment of pain in the postoperative period and leads to increased communication between patient and healthcare professionals and increases patient satisfaction levels [22].

For patients who are unable to self-report, e.g., dementia or patients who are unable to verbalize due to different reasons, standardized objective assessment tools have been designed and validated. One is the "Pain assessment in Advanced Dementia" (PAINAD) scale, the electronic pain assessment tool (e-PAT), Abbey pain scale, Dolopus-2, ADD Protocol, Observation Pain Behavioral tool, are some of the recommended tools for individuals with severe cognitive impairment [23]. Also Critical Care Pain Observation Tool and Behavioral Pain Scale are useful for pain assessment in patients who are unable to verbalize in critical care [23]. The surrogate measures such as opiate consumption may also be useful. The cardio-respiratory parameters are unreliable for pain assessment. The trends in pain assessment scores are more helpful than isolated pain scales [23]. An example of an assessment tool in non-verbal patients is illustrated in **Figure 3** [24]. This is the behavioral pain scale for assessing pain in critically ill patients on a ventilator [24]. A score of 0 indicates no pain, mild pain is indicated by a score of 0–3, moderate pain by a score of 3–6, and severe pain by a score of 6–8.

## **4. Goals of postoperative pain management**

Effective pain management not only decreases patient suffering but also reduces morbidity. It also facilitates early recovery and discharge from the hospital and reduces treatment costs. The goals of proper pain management are to improve the quality of life, facilitate postoperative recovery, reduce morbidity and improve functional outcomes, reduce hospital stay, prevent chronic pain, and promote patient satisfaction [21].

### **4.1 Principles for acute perioperative pain management**

Optimal perioperative pain management should done by charting out a pain management plan based on individual patient's needs. For this, one needs to evaluate every patient preoperatively to assess the medical history, presence of coexisting diseases, psychological conditions, history of chronic pain, substance abuse, and other concomitant medications [21]. A multimodal pain management plan, which includes pharmacological and non-pharmacological techniques, needs to be formulated based on the patient history. The patients and their families as well as the healthcare personnel need to be informed and educated regarding the pain management plan and its goals. In the postoperative period, tracking and documentation of pain are of utmost importance using an appropriate pain assessment tool. The medication and treatment technique should be altered based on the patient's response and the presence of any adverse events. Education of healthcare workers about proper storage, disposal, and record-keeping of opioids and tapering the doses after hospital discharge are important steps. Pain specialists may be consulted for patients with special needs and those with uncontrolled pain.

## **5. Treatment of acute postoperative pain**

Several options are available for treating postoperative pain including systemic (opioid and non-opioid) analgesics, regional analgesic techniques, and nonpharmacological methods. By taking into account each patient's preferences and making an individualized assessment of the risk and benefits of each treatment modality, the clinician can optimize the postoperative analgesic regimen for each patient.

## **6. Opioid medications**

The action of opioids is mediated through three types of opioid receptors, namely MOR (mu), DOR (delta), and KOR (kappa), with varying levels of affinity to each type of opioid receptor and also varying interactions with these receptors (agonists, partial agonists, antagonists). They exert analgesic effects, influence mood, and behavior, and affect respiratory, cardiovascular, gastrointestinal, neuroendocrine, and immune systems [25]. The analgesic efficacy of opioids is limited by the development of tolerance or due to side effects such as nausea, vomiting, pruritis, sedation, or respiratory depression. Opioids may be administered by subcutaneous, transcutaneous, transmucosal, or intramuscular routes, but the most important routes commonly employed are intravenous and oral. Opioids may also be delivered at specific anatomic sites such as intrathecal or epidural space. Long-acting opioids should be avoided in the immediate postoperative period except in patients who are already taking them before surgery [26]. When treating opioid-naïve adults, clinicians should avoid basal infusions with intravenous PCA, as it does not provide additional analgesia and is associated with nausea, vomiting, and respiratory depression [26].

## **7. Side effects of opioid medications**

The side effects of opioids are depicted in **Table 2**. The commonly used opioids and their routes of administration, side effects, and management are described briefly


**Table 2.** *Side effects of opioids [27].*

in **Table 3**. The incidence of life-threatening adverse events, such as respiratory depression, is rare and occurs within 24 hours. A systematic review of observational studies reported the incidence of postoperative opioid-induced respiratory depression as five in 1000 [27]. Also, those with preexisting cardiac disease, pulmonary disease, and obstructive sleep apnea are at increased risk of opioid-induced respiratory depression [27]. Other common side effects of opioid administration are sedation, dizziness, nausea, vomiting, constipation, physical dependence, and tolerance. Physical dependence and addiction are important concerns that can act as a barrier to pain management. Less common side effects are delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioids are constipation and nausea, which are difficult to manage. Mostly tolerance does not develop in them, especially to constipation. This may lead to discontinuation or under-dosing and inadequate analgesia.

## **8. Non-opioid medications**

These have been enlisted and described briefly in **Table 4** and are discussed as follows.

a. **Acetaminophen (Paracetamol):** It is used most often in conjunction with other medications as a part of multimodal analgesia protocol [16]. When used as a part of multimodal analgesia, it leads to faster recovery, higher levels of


**Table 3.**

*Commonly used opioids for acute pain: Routes of administration, side effects, and contraindications [28, 29].*

## *Acute Post-Operative Pain Management DOI: http://dx.doi.org/10.5772/intechopen.109093*


#### **Table 4.**

*Non-opioid group of drugs for postoperative pain management [28].*

satisfaction, fewer opioid adverse effects, and a decrease in the length of hospital stay. A statistically significant decreased mean consumption in mean cumulative 24-hour morphine consumption is observed with paracetamol compared with placebo after major surgery. When given prophylactically, it is associated with lesser postoperative nausea and vomittimg, and this is postulated to be due to superior pain control.


Used as sole agents, NSAIDs generally provide effective analgesia for mild to moderate pain. NSAIDs are also traditionally considered useful adjuvants to opioids for the treatment of moderate to severe pain. NSAIDs may be given orally or parenterally and are particularly useful as a component of a multimodal analgesia regimen.

a. **Gabapentinoids:** Gabapentin and pregabalin are antiepileptic drugs, also used in the treatment of neuropathic pain. These drugs cause depressed neuronal excitability due to the interaction with the α2δ calcium channel subunit. Also, there is enhanced descending inhibition and diminished descending serotonergic facilitation and modulation of the affective component of pain [25]. While prior studies [31] showed that there was a reduction in postoperative narcotic requirements with the benefits of decrease in the risk of postoperative nausea and vomiting. Recent meta-analysis however, showed no clinically significant improvement in pain relief with gabapentinoids [27]. However, there was a greater risk of dizziness and visual disturbance. A large range of the doses have been reported, ranging from 300 to 1200 mg for gabapentin and from 75 to 300 mg for pregabalin, given either preoperatively or postoperatively [31].

b. **Ketamine:** Ketamine is generally used as an intraoperative anesthetic agent. But, in subanaesthestic doses, it is a useful analgesic.The NMDA antagonistic properties of ketamine are responsible for attenuating central sensitization and opioid tolerance. The subanaesthetic dose of ketamine reduces the rescue analgesia requirement and pain intensity. In addition, perioperative ketamine reduces 24-hour patient-controlled analgesia (PCA) morphine consumption and postoperative nausea and vomiting and has minimal adverse effects. The side effects of ketamine are: hypersalivation, nausea, and vomiting, psychotomimetic effects such as vivid dreams, blurred vision, hallucinations, nightmares, and delirium. These act as deterrent to its routine use as an analgesic. Ketamine also reduces the likelihood of transition to chronic postsurgical pain. Although ketamine can be used effectively as part of a multimodal pain management regime currently, it is not recommended as a routine part of most ERAS postoperative pain strategies [2].

Patient-controlled analgesia (PCA): It is based on the idea that whenever the patient has pain, the patient can self-administer the analgesic drug, without having to request and wait for the healthcare staff [32]. PCA is useful in the acute pain setting where there is inadequate pain control from the initial opioid administration in the emergency department, and continued opioid dosing has been proven to improve patient outcomes [32]. Postoperative patients, especially those with indwelling nerve or epidural catheters, are ideal candidates for PCA. The ability of postsurgical patients to titrate and administer their pain medication allows for superior pain control compared to scheduled nurse dosing. Patients in labor pain are also well-established candidates for epidural PCA [32]. The pain associated with contractions, when exacerbated by induction agents such as oxytocin, can be adequately reduced and controlled by the patient [32]. A PCA device can be programmed for several variables such as demand dose (bolus), lockout interval, and background infusion. Compared to traditional analgesic regimens, PCA provides superior postoperative analgesia and improves patient satisfaction. Local anesthetics and opioids are commonly used medications for PCA. For intravenous PCA, opioids can be used as the sole analgesic. For epidural PCA, they are used or in combination with local anesthetics.

Opioids commonly used for PCA are: The pure Mu opioid receptor agonists (morphine, fentanyl, hydromorphone, meperidine, sufentanil, alfentanil, and remifentanil), Mu opioid receptor agonist-antagonists (butorphanol, nalbuphine, and pentazocine), and partial Mu opioid receptor agonists (buprenorphine, dezocine) [32]. Despite the availability of several analgesics, morphine is still considered the gold standard for PCA. The local anesthetics used for epidural analgesia and indwelling nerve catheter PCA are: bupivacaine, levobupivacaine, and ropivacaine [32]. Other medications added to intravenous PCA in order to reduce side effects and improve pain control include: ketamine, naloxone, clonidine, magnesium, ketorolac, lidocaine, and droperidol [32].

The opioid dosing is depicted in **Table 5**. However, the medication dose, which is given in PCA, must be tailored according to individual patients' analgesic needs. The patients should be oriented, alert, and demonstrate the ability to administer the demand dose for pain. The basal or continuous infusion is started if the patients are using frequent demand doses or if the pain is severe. The suggested basal dose is 30–50% of the average hourly dose [29]. For opioid-tolerant patients, one should consider the patient's current opioid regimen, clinical condition (cause and its severity), side effects from opioids, baseline sedation, and need for opioid rotation. First,


#### **Table 5.**

*Intravenous patient-controlled analgesia for opioid-naïve patients [29].*

the total opioid dose used in the previous 24 hours is estimated, and then an equianalgesic opioid conversion table is used for calculating the IV dose of opioid intended for use in PCA. The hourly dose is the new IV dose from this step divided by 24 hours to obtain the basal/hourly dose. The PCA demand dose is 10–20% of this new opioid dose as PRN every hour [29].

## **9. Neuraxial analgesia**

The analgesia provided by epidural is site-specific and superior to that with systemic opioids. The use of this technique may even reduce morbidity and mortality [10].


## **9.1 Analgesic drug for epidural**


infusion of morphine may provide superior analgesia with fewer side effects compared to intermittent doses.

**Local anesthetic and opioid combinations:** The epidural infusion of LA-opioid combination is advantageous than the infusion of LA or opioid alone. This combination provides superior postoperative analgesia, limits time for regression of sensory blockade, and decreases the dose of local anesthetic. Continuous epidural analgesia of LA-opioid combination provides superior analgesia than the intravenous patientcontrolled analgesia with opioids [14].

**Patient-controlled epidural analgesia (PCEA):** Like intravenous PCA, PCEA allows individualization of postoperative analgesia requirements and may have several advantages over continuous epidural infusion, including lower drug use and better patient satisfaction. PCEA may also provide analgesia superior to than intravenous PCA [15]. PCEA is a relatively safe and effective technique for postoperative analgesia.

The drug doses for continuous epidural infusion and PCEA drug doses are given in **Table 6**.

**Adjuvant drugs**: A variety of adjuvants may be added to epidural infusion to enhance analgesia while minimizing side effects. Clonidine acts centrally as an agonist on alpha-2a adrenergic receptors [33]. Clonidine also mediates its effects through the spinal dorsal horn alpha-2 receptors via the primary afferents, interneurons, and through the descending noradrenergic pathways. Clonidine enhances the analgesic activity of opioids and local anesthetics and prolongs the duration of blocks [33, 34]. Two proposed mechanisms for the analgesic effects produced by clonidine include the reduction of glutamate and excitatory neuropeptide release from central afferent terminals, as well as the hyperpolarization of dorsal horn neurons [33]. Epidural dose of clonidine is 5–20 micrograms/hour. Its side effects are hypotension and bradycardia [1].

**Location of epidural catheter:** The insertion of an epidural catheter congruent to incision dermatome results in optimal postoperative analgesia with lesser side effects (lower extremity block, urinary retention) and a decrease in morbidity [10, 18]. There is a summary of neuraxial opioids, their adverse effects, and management of same in **Table 7**.


**Table 6.**

*Local anesthetics dose for postoperative patient controlled anaesthesia [28].*


**Table 7.**

*Adverse reactions from neuraxial opioids and treatment.*

## **10. Regional analgesia**

The use of peripheral nerve blocks (PNBs) as a single injection or as continuous infusion can provide site-specific analgesia superior to the systemic opioids and may even result in improvement in various outcomes [14]. The PNBs may have several advantages over systemic opioids (i.e., good analgesia and lesser opioid-related side effects) and neuraxial techniques (i.e., less risk of spinal hematoma, better hemodynamic instability). All this can lead to faster recovery, reduced stay in the hospital, decreased incidence of nausea and vomiting, early rehabilitation, and greater patient satisfaction [34]. Absolute contraindications to the use of peripheral nerve blocks

include allergy to local anesthetics, inability to cooperate due to dementia or similar conditions, or patient refusal. PNBs should not be given if there is an active infection at the injection site, or if there are preexisting neural deficits in area of distribution of the block, and in patients with coagulopathies or on antithrombotic drugs [35].

## **11. Upper extremity blocks**

The regional blocks can be given using a nerve stimulator or ultrasound visualization for locating the nerves. The nerve stimulator causes muscle contractions when the corresponding nerve is stimulated. Commonly used local anesthetics include bupivacaine and ropivacaine. Once the local anesthetic is placed, the patient can expect pain relief and limb heaviness for the duration of the local anesthetic action and adjuncts used [36].


potential to cause pneumothorax, making it an ideal option for day -case surgery [39]. However, the general risks of accidental intravascular and intraneural injection still exist.


## **12. Lower extremity blocks**

• **Lumbar plexus block:** The lumbar plexus (LP) is formed within the body of the psoas major muscle by the four spinal nerves of L1–L4. In 60% of people, the lumbar plexus receives a contribution from the nerve root of T12 as well [44].

The LPB is used to provide analgesia following injuries or surgeries of the hip or thigh (e.g., acetabular fractures, femoral neck or mid-shaft fractures, hip replacement, hip arthroscopy, knee replacement). It has also been used for chronic pain conditions such as herpes zoster. It is important to note that the LPB is unlikely by itself to produce complete anesthesia for hip replacement surgery due to the innervation of the posteromedial hip capsule deriving from branches of the sacral plexus and sciatic nerve [44].


## **13. Truncal blocks**

Several non-epidural/truncal regional analgesia techniques can be used for management of postoperative thoracic and abdominal pain. Truncal blocks include the blocks of chest wall and anterior abdominal wall. The chest wall blocks are thoracic paravertebral, intercostal blocks, pectoral blocks, serratus anterior plane block, suprascapular, interpleural analgesia, and cryoanalgesia. The blocks of anterior abdominal wall are transverses abdominis plane block (TAP), rectus sheath block, quadrates lumborum blocks, erector spinae blocks, ilioinguinal, iliohypogastric nerve [52]. The ultrasound-guided regional blocks have revolutionized the management of perioperative pain. The unique feature of this is that no nerve or plexus needs to be identified. The local anesthetic is injected into a particular muscle plane, which spreads and reaches the intended nerves. The current research is leading us to an era where ultrasound will become a basic necessity for practice of regional anesthesia [52].

## **13.1 Chest wall blocks**


the plane between pectoralis minor and serratus anterior muscles often at the level of third rib [56].

## **13.2 Blocks of anterior abdominal wall**


• **Ilioinguinal and iliohypogatric nerve blocks:** These blocks are used for postoperative analgesia in lower abdominal surgeries and cesarean section. The block involves the blocking of ilioinguinal and iliohypogastric nerves in the plane between the transversus abdomini and internal oblique muscles [63]. In the conventional blind method, this plane is reached by the "click" felt during needle insertion at this point. With this blind method, there are possibilities of missing the plane between the transversus abdominis and internal oblique. Also there are chances of complications such as bowel perforation, injury to blood vessels, urinary retention, and femoral nerve blockade [63]. Ultrasound-guided procedure avoids these complications and helps in accurate drug placement after identifying the nerves and thus lesser dose of LA [63].

## **14. Adjuncts to regional nerve blocks**

The duration of action of local anesthetics in PNB varies but may last up to 24 hours. Patients who have had a single-shot PNB may complain of slightly greater postoperative discomfort between 16 and 24 h compared with those who have had only systemic analgesics [64]. Rebound pain may occur after single-shot PNBs, resulting in sleep disturbances, difficulties employing enhanced recovery and physiotherapy protocol, and increased consumption of opioids and related side effects [64]. Hence, strategies have been sought to extend the benefits of single-shot PNBs beyond the maximum of 8–16 h. A continuous PNB involves the percutaneous insertion of a catheter adjacent to a peripheral nerve, plexus, or fascial plane, followed by the administration of LA through the catheter [64]. Such a procedure may involve problems such as inaccurate catheter tip placement and secondary block failure; catheterrelated mechanical nerve irritation, catheter knotting, migration, obstruction or shearing, fluid leakage or inflammation at the insertion site of the catheter; bacterial catheter colonization; infusion pump malfunction; myonecrosis with repeated large boluses of bupivacaine; and LA systemic toxicity [64]. The use of "perineural adjuncts" is technically simple and effective alternative to the continuous PNBs in order to extend the benefits of single-shot PNBs. The term perineural adjuncts refers to the co-administration of pharmacological agent(s) with LA(s) around a peripheral nerve, plexus or fascial plane with the aim of affecting the characteristics of the resulting block [64]. Over time, the number of potential perineural adjuncts has increased to a wide variety of drugs.

Several drugs have been used to improve the quality and duration of block.

1.**Dexamethasone**: It is a potent long-acting glucocorticoid with minimal mineralocorticoid activity. It stimulates the glucocorticoid receptors located on the cell membranes of neurons after perineural administration, increasing the expression of inhibitory K<sup>+</sup> channels and thereby decreasing the excitability of and neuronal transmission in nociceptive unmyelinated C-fibers. It may be that its actions are mediated via localized vasoconstriction or systemic antiinflammatory effects after absorption through the vasculature. Dexamethasone must be administered as a preparation without preservatives such as benzyl alcohol and propylene, both of which can cause neurolytic effects [64]. Studies have demonstrated that perineural dexamethasone was associated with an increase in the mean duration of analgesia, decrease in pain scores at rest and on movement, and reduction of cumulative morphine consumption at 24 hour [ 64].


7.**Magnesium** is an *N*-methyl-D-aspartate (NMDA) receptor antagonist that has been found to increase the excitation threshold in peripheral nerves, more so in myelinated Aβ than unmyelinated C-fibers. Its mechanism of action after perineural administration could be secondary to the effects of its positive divalent charge on the neuronal membrane or its role as a physiological calcium antagonist [64]. Perineural magnesium was associated with an increase in the mean duration of analgesia by approximately 2 h, duration of sensory block by 1.75 h and duration of motor block by 1.5 h. Perineural magnesium did not increase the risk of PONV [64].

Drugs such as fentanyl, morphine, ketamine, tramadol, midazolam, and neostigmine are not used as perineural adjuncts in PNBs because of conflicting or limited evidence and worries about their potential for adverse effects or neurotoxicity [64].

## **15. Non-pharmacological methods for acute pain**

The non-pharmacological methods of pain management can be divided into physical interventions and psychological interventions. Physical/sensory interventions are patient-specific, they inhibit nociceptive input and pain perception. They include methods such as massage, positioning, rest, ice/heat therapy, acupuncture, TENS, accupressure, etc. [68]. The psychological interventions consist of therapies such as cognitive-behavioral therapy, mindfulness-based stress reduction, acceptance and commitment therapy, guided imagery, biofeedback, music therapy, and meditation etc. [69]. These can act as an important adjuvant for pain management. It has the advantage of being relatively inexpensive and safe. It helps decrease fear, distress, and anxiety and is convenient The non-pharmacological methods have significant and often enduring efficacy in pain management and can be employed alone or in combination with pharmacological methods [70]. A few of the common nonpharmacological techniques are discussed below.


Trans-electrical nerve stimulation (TENS) and acupuncture may provide postoperative analgesia, decreased postoperative opioid requirements, reduced opioidrelated side effects, and attenuate activation of sympathoadrenal system. In general, all of these techniques are relatively safe, noninvasive, and devoid of systemic side effects seen with other analgesic options [68–71]. Cognitive therapy and behavioral therapy may be efficacious in reducing pain and alleviating psychological factors associated with pain.

## **16. Considerations for acute postoperative control in specific patient populations**

**Opioid tolerant patients:** These patients are chronically on opioid for preexisting pain or may be taking opioids for recreational purposes. Opioid tolerance is characterized by a decreased responsiveness to an opioid agonist such as morphine and is

### *Acute Post-Operative Pain Management DOI: http://dx.doi.org/10.5772/intechopen.109093*

usually evident by the need to use increasing doses to achieve the desired effect [72]. Patients who are taking opioids for management of cancer pain or chronic non-cancer pain or who have an opioid addiction may become opioid-tolerant. Acute pain management in opioid-tolerant patients should ideally be done by a multidisciplinary team comprising pain specialists, physicians, psychologists, trained nursing staff, etc. A meticulous evaluation, proper coordination, and effective interdisciplinary communication are needed. So also, there should be effectual interaction between each discipline and the patient for a successful outcome. The aims of management in opioidtolerant patients are to promote optimal perioperative analgesia, prevent withdrawal syndromes, and deal with any related social, psychiatric, and behavioral issues [73]. Patients with an opioid dependency have three challenges to effective pain management: : [i] opioid-induced hyperalgesia (OIH), resulting in increased pain sensitivity; [ii] opioid tolerance, leading to reduced efficacy of opioids used to treat pain; and [iii] opioid withdrawal, producing sympathetic stimulation and heightened stress responses if the usual opioids are not given [73]. There is a high prevalence of psychiatric disorders in those with drug dependence, with more than 50% of patients showing evidence of conditions such as anxiety disorders and affective disorders, including depression. Such comorbidities may further complicate patients' behavior and their interaction with staff while in the hospital [74].

Early identification through a careful assessment and history in patients with opioid tolerance is essential for adequate pain-management planning. Postoperative pain management should start at the time of preoperative assessment, even prior to admission, and should include appropriate discharge planning [72]. If opioid tolerance has not been identified preoperatively, it should be suspected if the following triad is present after surgery: 1) elevated pain scores, 2) high opioid use, and 3) low incidence of side effects (apart from sedation). A multimodal pain regimen with a combination of pharmacologic and non-pharmacologic approaches is ideal. Opioids are the drugs of choice for severe pain and are also useful to manage moderate pain. However, multimodal approach with acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and adjuvants such as ketamine also provides effective pain relief. Patients with opioid tolerance may require more opioids than opioid-naïve patients. The dose of opioids should be tailored as per the individual need of the patient so as to achieve adequate analgesia without causing harmful side effects, such as over-sedation or respiratory depression. "Opioid rotation" is the substitution with a different opioid when one opioid does not provide desired level of analgesia even with increasing doses. This may be employed as required in patients with opioid tolerance, as crosstolerance is uncommon. The recommended approach for opioid rotation is to initially substitute with one-half to two-thirds equianalgesic opioid and then monitor for safety and effectiveness. One needs to exercise caution while switching from a longacting opioid to a short-acting one as this may precipitate withdrawal symptoms in the patient [73].

Opioid-related side effects are less common in opioid-tolerant patients; however, if opioid therapy is selected as analgesia of choice in these patients, monitoring for side effects or complications related to opioid therapy is also important. The risk of adverse drug events is more if opioid dosage is increased rapidly, even if the patient is opioidtolerant. In fact, opioid-tolerant patients are more susceptible to the sedative properties of opioids [73].

For opioid-tolerant patients, patient-controlled analgesia (PCA) offers a convenient method of delivery, as it minimizes the risk of under treatment, allows self-titration, and negates possible conflicts with nursing staff. Additionally, a

retrospective study found that opioid-tolerant patients who had PCA were less likely to report adverse effects—with the exception of sedation—compared with the opioidnaïve group [72]. In order to calculate the PCA bolus dose and background infusion rate, an individual preoperative "fentanyl challenge" is done to the point of respiratory depression followed by pharmacokinetic modeling to predict intra and postoperative opioid requirements [72]. An alternative and simple method is to calculate the PCA bolus dose on the basis of the dose of long-term opioid already being taken. The use of PCA background infusions is to be avoided in the opioid-naïve, because of the increased risk of respiratory depression. However, in opioid-tolerant patients, the PCA infusion is used to deliver the equivalent dose of long-term oral opioid if oral administration is not possible. Various studies have shown that gabapentin and pregabalin, paracetamol, non-steroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and alpha-2 agonists all lessened the opioid tolerance [73].

Opioid withdrawal can occur in opioid-dependent patients receiving a reduced amount of their usual opioid or if an opioid antagonist is given. The patients may exhibit at least three of these signs and symptoms: dysphonic mood, nausea, vomiting, diarrhea, muscle aches, rhinorrhoea, lacrimation, pupillary dilation, piloerection, sweating, yawning, fever, and insomnia. These may impair social, occupational, and other important areas of functioning [73]. The central principle of withdrawal management is to prevent its development, providing more stability for patients and reducing psychological and physiological stress. Clonidine has long been used to manage opioid withdrawal symptoms [74]. The most commonly used drugs for OST (opioid substitution therapy) are sublingual buprenorphine and oral methadone. These drugs reduce the level of drug abuse and related behavior and provide stability to the drug users and their families. The duration of withdrawal suppression is about 24 hours, so the dose can be continued once a day or may be given in two or three divided doses [73]. The drugs used for OST will not provide analgesia, and hence, withdrawal prevention and analgesia provision should be considered as separate entities. Methadone may predispose patients to the ventricular arrhythmia, the torsades de pointes as it can cause prolongation of the corrected electrocardiographic QT interval. So appropriate monitoring is needed. When buprenorphine, which is a partial agonist with a high-binding affinity at the mu-opioid receptor, is used as OST at higher doses of 16–32 mg, there is minimum free receptor availability. In such cases, the additional pure opioid agonists including drugs such as heroin would provide no analgesic effect. Hence, buprenorphine should be stopped during perioperative period to allow receptor accessibility for opioids used for analgesia [73].

Patients with pain taking long-term opioids, those abusing heroin, and those on methadone and buprenorphine substitution therapy may develop hyperalgesia. Multimodal analgesia should be optimized by adding opioid-sparing analgesics such as paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs, or cyclooxygenase-2 inhibitors, using local anesthetic regional techniques, whereas ketamine attenuates OIH in patients on long-term opioids. Studies have demonstrated that gabapentin and pregabalin reduce OIH in animal models, human volunteers, and patients [74]. Similarly, there is evidence that alpha-2 agonists—clonidine and dexmedetomidine—may also decrease OIH, whereas experimental results indicate that COX- 2 inhibitor can also impart this benefit [74].

**Pediatric patients:** Pediatric patients continue to be undertreated for acute pain. There is a common myth that pediatric patients do not feel pain or they do not remember the pain. Control of pain in pediatric patients is important because poor pain control may result in increased morbidity and mortality. Different treatment modalities have

evolved, and multimodal analgesia has become the treatment of choice not only involving a pharmacological approach but also non-pharmacological approaches (e.g., regional analgesia, rehabilitation, cognitive behavioral therapy, virtual reality).

Special scales are available for children to self-report their pain. One important scale is Children and Infants Postoperative Pain Scale (CHIPPS) where scores of 0–2 are assigned as indicators of level of pain for crying, facial expression, posture of the trunk, posture of the legs, motor restlessness, etc. [12]. The other scales are Faces Pain Scale-Revised, pain word scale, Revised-Face Legs Activity Cry Consolability (r-FLACC), Premature Infant Pain Profile, Neonate Facial Coding system, Neonate Infant pain scale, Maximally Discriminative Facial Movement Coding System.

Oral and rectal route is preferred in children for administering analgesics [12]. Intramuscular injections are to be generally avoided for pain and fear associated with injection and unpredictable absorption of drug [12]. Regional nerve block, neuraxial blocks, peripheral nerve blocks, local infiltration analgesia with general anesthesia may improve postoperative pain management in pediatric patients. Intravenous patient controlled analgesia can be effectively used with prior education of patient about its use in children aged over 5–6 years [1].

Acetaminophen has antipyretic and anti-inflammatory properties. Its mechanism of action is through COX3 enzyme (inhibition of prostaglandin synthesis) inhibition, cannabinoid agonist, NMDA agonist, and activation of descending serotonergic pathways in CNS and via inhibition of prostaglandin synthesis [75]. NSAIDs are used commonly in pediatric population. Their use in pediatric population has demonstrated adequate pain control, opioid-sparing effect, and decrease in postoperative nausea vomiting [75, 76]. Use of ketorolac for pain control after tonsillectomy is associated with more risk of postoperative bleeding. However, that risk is counterbalanced with decreased PONV, sedation, and respiratory depression [75]. Gabapentinoids are not recommended in children for acute postoperative pain as per the current evidence [75]. Ketamine used in perioperative period in pediatric patients could have the potential of decreasing hyperalgesia, central sensitization, and reverse opioid tolerance [75]. The clinical scenarios where ketamine could be used are patients at high risk of developing postsurgical neuropathic pain, opioid-tolerant patients, patients who are more susceptible to develop opioid-related side effects, patients with chronic pain conditions, etc. Intravenous lidocaine should be avoided in patients weighing <40 kg [75]. Dexmedetomidine is useful adjunct to decrease postoperative pain with an opioid-sparing effect and decrease in emergence delirium [75].

**Obese patients:** These patients present various anatomic and pathophysiologic challenges in pain management. A major challenge is their altered pharmacokinetic profile, which accompanies physiologic changes in this population, which make obese patients more susceptible to respiratory depression and sleep apnea if opioids are used. The goal of pain management in such patients is provision of comfort, early mobilization, and improved respiratory function without causing respiratory compromise [26]. Recommendations are multimodal analgesic management, preference for regional techniques, avoidance of sedatives, noninvasive ventilation with supplemental oxygen, early mobilization, and elevation of the head.

## **17. Discussion**

Optimal treatment of postoperative pain requires multidisciplinary approach and a dedicated team for providing a round-the-clock service [12]. Each surgical procedure

produces varying degrees of pain. A comprehensive and effective pain management plan includes the appropriate care of individual patients' needs during the various stages of perioperative period. The patients and the caregivers should be educated about the importance of postoperative pain management. The acute pain teams should assess patients preoperatively and plan a pain management protocol. There should be regular assessment, treatment, and documentation of pain. The staff should be given training and continued education about physiology of pain, pathophysiology, pharmacology, monitoring routines, etc. All this is possible if an acute pain service is set up, which is a dedicated organization for acute pain management. Before establishing the acute pain service, an audit should be conducted for studying the effectiveness of the current pain management protocols, and later comparisons must be done after the establishment of pain service. Daily pain ward rounds should be started, which provides an ideal opportunity to teach service providers, address misconceptions, discuss pain-related issues with patients, and adopt prescription charts to improve pain control as needed. Various studies have shown improved pain scores after establishment of APS. The studies have shown that not only the newer techniques that improved postoperative pain but also the systematic and planned application of already existing ones [77].

## **18. Conclusion**

Untreated postoperative pain can have untoward consequences not only on individual patient health but also adversely affects the health care system. Optimal pain management improves the quality of life, facilitates recovery, and decreases morbidity. A multimodal, evidence-based, and procedure-specific, individualized analgesic regimen with minimum side effects should be the standard of care. Such a regime is an integral part of ERAS, which facilitates the important ERAS milestones such as early mobilization and oral feeding. Assessment, documentation of pain and response to its treatment are vital for effective postoperative pain management. Patient-controlled intravenous and epidural analgesias have the advantages of superior pain relief and improved patient satisfaction. The regional techniques have become an integral part of pain management programs. The use of ultrasound-guided techniques has made the regional techniques hassle-free with potent analgesia and lesser possibility of complications. Besides the pharmacological methods, which are routinely used, nonpharmacological methods should also be integrated into the postoperative pain management plan. These techniques are relatively inexpensive and safe and help decrease fear, distress, and anxiety and can be instituted by the nursing staff as well as the patients' caretakers. The patients with special needs such as the opioid-tolerant patients, patients in extremes of age, and obese patients, etc., need a well-planned approach under the care of experienced and expert healthcare staff. The institutionalized and dedicated team approach for acute pain management in the form of Acute Pain Service will go a long way in incorporating all the above said principles, thus improving postoperative pain management and patient satisfaction.

*Acute Post-Operative Pain Management DOI: http://dx.doi.org/10.5772/intechopen.109093*

## **Author details**

Samina Khatib<sup>1</sup> \*, Syed S.N. Razvi<sup>2</sup> , Mudassir M. Shaikh<sup>3</sup> and Mohammad Moizuddin Khan<sup>4</sup>

1 Department of Anesthesiology, Government Cancer Hospital, Aurangabad, Maharashtra, India

2 Department of Physiology, Parbhani Medical College, Parbhani, Maharashtra, India

3 Department of Anesthesiology, JIIU's Indian Institute of Medical Science and of Research, Maharashtra, India

4 Department of Physiology, College of Medicine, Dar-ul-Uloom University, Riyadh, Saudi Arabia

\*Address all correspondence to: ssr.anesth@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 7
