5.1. In adult patients

Pain management in dental practice is usually an unpredicted challenge and is highly related to individual patient response to pain, the expectations of the patient, pathophysiological mechanism of pain and selection of analgesic drugs. Pain relief is a very important precondition during interventional dental treatment and ensures a trustful and comfortable relationship between patients and the dental doctor [49].

Almost all dental procedures are accompanied by pain of different intensity, nature and length and treatment of pain pre- or postdental intervention is an integral part of dental treatment [27]. Efficient pain treatment during dentistry healthcare is mandatory for the achievement of desirable clinical outcome and successful dental clinical treatment. Usually in the preparation phase of patient, before the initiation of dentistry interventions, the use of local anesthesia ensures the control of patient pain [50].

The clinical evidence shows that local anesthesia results in the relief of pain during intraoperative dental period and shortly for postoperative pain and dental doctor should consider effective pain management during all stages of dental treatment. As the dental pathological process usually involves inflammation, the effect of local anesthesia is reduced due to prostaglandins interference with tetrodotoxin-resistant receptors, which diminishes the nerve responses to local anesthesia [51].

For effective dental pain management, dental doctors should address attention to disease, patient and finally to available nonpharmacological and pharmacologically effective treatment options.

The dental doctor should initially assess the pathological process of dental tissue in order to understand the mechanism of disease and to predict the health status of the patient. It is very important to define the etiology of the pathological process, especially to determine the eventual inflammatory response [52].

There is reported evidence that premedication with NSAIDs drugs such as ibuprofen or indomethacin significantly increases the level of alveolar nerve block anesthesia in dental interventions (78 and 62%) compared to placebo (32%) [53]. During the process of soft tissue trauma, a pain response occurs and this warrants the measures for pain treatment.

In dental operative procedure, preoperative administration of medication, including analgesic drugs, is recommended in order to diminish postoperative pain and to reduce the need for postoperative analgesic.

An effective strategy for dental pain treatment is based on the dynamic process of creation of a logical treatment map, which is built by the methodology of conceptualization to visualize the relationship between patient symptoms, dental interventions, therapeutic treatment and patient's needs and expectations.

However, side effects should be taken into consideration. Most significant opioid effects are mediated through μ and κ receptors including for morphine and other semisynthetic and synthetic drugs such as meperidine, methadone, hydrocodone, oxycodone, fentanyl,

Pain management in dental practice is usually an unpredicted challenge and is highly related to individual patient response to pain, the expectations of the patient, pathophysiological mechanism of pain and selection of analgesic drugs. Pain relief is a very important precondition during interventional dental treatment and ensures a trustful and comfortable relation-

Almost all dental procedures are accompanied by pain of different intensity, nature and length and treatment of pain pre- or postdental intervention is an integral part of dental treatment [27]. Efficient pain treatment during dentistry healthcare is mandatory for the achievement of desirable clinical outcome and successful dental clinical treatment. Usually in the preparation phase of patient, before the initiation of dentistry interventions, the use of local anesthesia

The clinical evidence shows that local anesthesia results in the relief of pain during intraoperative dental period and shortly for postoperative pain and dental doctor should consider effective pain management during all stages of dental treatment. As the dental pathological process usually involves inflammation, the effect of local anesthesia is reduced due to prostaglandins interference with tetrodotoxin-resistant receptors, which diminishes the

For effective dental pain management, dental doctors should address attention to disease, patient and finally to available nonpharmacological and pharmacologically effective treatment

The dental doctor should initially assess the pathological process of dental tissue in order to understand the mechanism of disease and to predict the health status of the patient. It is very important to define the etiology of the pathological process, especially to determine the even-

There is reported evidence that premedication with NSAIDs drugs such as ibuprofen or indomethacin significantly increases the level of alveolar nerve block anesthesia in dental interventions (78 and 62%) compared to placebo (32%) [53]. During the process of soft tissue

In dental operative procedure, preoperative administration of medication, including analgesic drugs, is recommended in order to diminish postoperative pain and to reduce the need for

trauma, a pain response occurs and this warrants the measures for pain treatment.

buprenorphine, pentazocine and tramadol.

118 Pain Relief - From Analgesics to Alternative Therapies

5.1. In adult patients

5. Principles of dental pain management

ship between patients and the dental doctor [49].

ensures the control of patient pain [50].

nerve responses to local anesthesia [51].

tual inflammatory response [52].

postoperative analgesic.

options.

Furthermore, there is available misleading information showing that naproxen sodium has a superior analgesic efficacy compared with ibuprofen at postdose interval from 1 to 12 h [28, 54, 55]. The important analgesic agents for use in dentistry are also para-aminophenol derivative such as paracetamol (acetaminophen). Administration of individual paracetamol is recommended in mild form of dental pain only when the NSAIDs are contraindicated. Otherwise, there is clinical evidence showing that ibuprofen in doses 200–512 mg versus paracetamol 600–1000 mg is superior in relief of postoperative pain. The novel strategy for pain treatment is the use of combination containing ibuprofen and paracetamol. This combination is more effective than the effect of individual analgesic when taken at 6 h after dental intervention.

The evidence shows that the most frequent doses of respective analgesics prescribed in clinical practice are 400 mg for ibuprofen and 1000 mg for paracetamol [56]. For more intensive pain when the administration of individual NSAID analgesic or combination of NSAID and paracetamol are not effective, the administration of an opioid and NSAIDs is recommended. The analgesic effect achieved by this drug combination is higher than the doubling of dose of either analgesic administered alone [57].

There are several possibilities of combinations of nonnarcotic and narcotic analgesics, which might be effective for the treatment of dental pain. The mostly used analgesic combinations in dental pain management are acetaminophen-codeine (300 mg + 30 mg), oxycodone-ibuprofen (5 mg + 400 mg), or hydrocodone-acetaminophen (5 mg + 325 mg or 7.5 mg + 500 mg) [58]. The main paradigm for treatment of dental pain is the appropriate selection of effective analgesic, at lower possible dose with the lowest probability for side effects (Table 1).



Table 1. General use of analgesic drugs in the different types of pain in dentistry.

#### 5.2. Elderly patients

The strategy for dental pain treatment in elderly patients is generally the same as treatment of pain in general adult population with some differences due to age-related changes principally in physiology and pharmacokinetics in this group of patients. Clinical practice shows that elderly patients are more prone to feel the pain than adult patients and frequently are undertreated.

In the management of dental pain the clinician should consider several factors:


The strategy of dental pain relief in elderly patients should be based on several principles and initially we should select the available nonpharmacological measure for pain treatment. If nonpharmacological options are ineffective we need to carefully select the appropriate analgesic drug considering the risk/benefit ratio. After selection of appropriate analgesic the initiation of therapy should start with dose titration starting with lowest dose increasing slowly to effective safe dose. The analgesic therapy should be monitored closely by dental clinicians in order to achieve a successful pain relief and to prevent the possible side effects. The course of analgesic therapy should be as short as possible and also need to be stopped in case of any sign of infectivity and persistency of pain.

For pain relief in elderly patients, the recommended analgesic drug is paracetamol. In case of hepatic or renal functional disorders, dose adaptation is recommended, while in terminal hepatic insufficiency, the administration of paracetamol is contraindicated, in this case the use of NSAIDs is preferred, but these patients need close monitoring. NSAID should be given to elderly patients in the lowest effective dose and in short periods of time in order to avoid the possible side effects of these analgesic drugs. In case of severe dental pain, the use of opioid analgesic is indicated. Usually, oral opioids in the lowest possible doses, such are tramadol and some others, are used. In order to use the opioid analgesic drugs in the lowest doses, the combination of paracetamol and tramadol or codeine is recommended. In elderly patients with intensive dental pain, the strong opioid of choice is morphine [61].

## 5.3. Children

5.2. Elderly patients

Dental surgery—impacted third molar surgery and Dental surgery—dental root

After third molar extraction Oral surgical or endodontic

Intensive dental pain Oxycodone/

120 Pain Relief - From Analgesics to Alternative Therapies

Temporomandibular

Nontraumatic dental Conditions with severe pain

canal treatment

treatment

disorders

undertreated.

neurodegenerative diseases.

The strategy for dental pain treatment in elderly patients is generally the same as treatment of pain in general adult population with some differences due to age-related changes principally in physiology and pharmacokinetics in this group of patients. Clinical practice shows that elderly patients are more prone to feel the pain than adult patients and frequently are





macological treatment with increased risk of drug interactions and side effects.

family and nursing health care personnel should be considered.

In the management of dental pain the clinician should consider several factors:

Type of pain in dentistry Analgesic drug Dosing (Adults) Adverse effects

100/1000 mg single oral dose with 8 h observation 600/1000 mg 30 minutes before procedure or after surgery

10 mg every 4–6 h 5 mg every 6 h 60 mg every 6 h 50–75 mg 4–6 h

5/400 mg every 6 h 5/500 mg every 6 h 5/325 mg or 7.5/500 mg

every 4–6 h

Nausea, drowsiness headache

Nausea, sedation, dizziness, constipation, addiction, sleep disorders

Nausea, sedation, dizziness, constipation, addiction, sleep disorders

Diclofenac/ Paracetamol Ibuprofen/ Paracetamol

Hydrocodone Oxycodone Codeine Tramadol

Ibuprofen Oxycodone/ Acetaminophen Hydrocodone/ Acetaminophen

Table 1. General use of analgesic drugs in the different types of pain in dentistry.

generally at three-fourths of dose of adult patients [59].

In clinical pediatric care, effective pain management is a standard routine approach and is mandatory in the modern concept of health care. It is accepted that the basic mechanism of pain in infants and children is substantially similar to adults with some exception in neonates related to some differences in physiological mechanism of pain, which is characterized with slower and less precise conduction of pain but without significant differences in pain perception [62].

Modern pain management for children addressing the medical conditions and surgical interventions and postoperative period has substantially advanced over the last two decades.

Advanced pain management strategy is based on two main directions, including the interventional pharmacological and nonpharmacological approach. The interventional pharmacological approach consists of the use of NSAIDs and other analgesics administered via different routes of administration (i.v. bolus administration, continuous infusion, rectal, transdermal and other routes of administration); local anesthetics, epidural anesthesia and peripheral nerve blockade. Nonpharmacological measures consist of health education of children and psychological approach to release the perception of fear and other behavioral problems in children patients, breathing techniques, hypnosis, transcutaneous electrical nerve stimulation, guided imagery, acupuncture, relaxation and other techniques to relieve the pain [63].

Pain management strategy in children consists of several principles, which reflect the differences between children and adult pain treatments. The strategy of pain relief should focus on the prevention of pain and this ensures better treatment success before painful procedures. Usually this starts with preparing the child and the family in advance, in order to reduce fear and anxiety before intervention and applying patient-controlled analgesia (PCA). In case of major surgical interventions the treatment of predicted pain after treatment in children can continue with oral analgesics depending on patient needs.

Dental clinicians should assess the pain intensity using the appropriate children pain scale. It is recommended to use the FLACC scale for pain measurement in pediatric patients aged 1 month to 3 years, while for children above 3–7 years the Wong-Baker pain rating scale is used (Figure 1), which has demonstrated to be more sensitive compared to visual analogue scale. For children above 7 years, the Visual Analogue/Numerical Rating Scale is used. A universal measuring tool does not exist but according to a systematic review FACES scale demonstrated to be effective in children from 3 to 12 years in which gradient of emotions cartoons are chosen by children based on their level of pain. There is also another measurement, such as Oucher pain scale, which does not differ much from the others, but it is more specific in different racial face expressions such as Caucasian, African American, Hispanic, First Nations Boy and Girl and Asian Boy and Girl [64–69].

Figure 1. Wong-Baker faces pain rating scale explains to the person that each face is for a person who has no pain (hurt), some, or a lot of pain by asking the person to choose that best describes how much pain he has.

Multimodal and multiapproach therapy is the cornerstone of pain management in children. This technique uses different analgesia and nonpharmacological complementary approach in order to enhance the pain control and minimize drug-induced adverse effects. This method supports the use of combined nonopioid (NSAIDS, other analgesic agents, local anesthetics, alpha2-adrenergic agonists, voltage-gated calcium channel alpha-2 delta-proteins) and opioid analgesics and other agents in smaller doses in order to prevent the clinical manifestations of drugs side effects [70]. Dosage calculations of analgesics for children are based on mg/kg body weight administered by intravenous, oral and rectal route, while intramuscular injections should be avoided. It is recommended that severe pain is treated by infusions, PCA and other routes of continuous analgesic administration.

Pain treatment options in neonates and premature infants should avoid the use of opioid analgesics. However, in cases when there is no other option, opioid analgesics should be closely monitored in intensive care units. In this group of infants, opioids are more prone to develop dependency and depression of cardiorespiratory functions.

The mainstream in pharmacological pain treatment consists of administration of NSAIDs, paracetamol. Usually it is recommended to use paracetamol (infant dose is 10–15 mg/kg/dose every 6–8 h, pediatric oral dose 10–15 mg/kg/dose every 4 h), ibuprofen (10 mg/kg/dose every 6 h) and diclofenac (1 mg/kg/tds or 1.5 mg/kg/bd, maximum daily dose is 3 mg/kg). While naproxen (2 years or older: 5 mg/kg orally twice a day; 12 years or older: 220 mg orally every 8–12 h) is indicated more in inflammatory diseases. In modalities of analgesic therapy combinations the dosage of individual analgesics are decreased.

For more intensive pain the use of opioids is recommended. Codeine (0.5–1 mg/kg every 4–6 h) is a weak opioid analgesic and to increase the analgesic effect it is often combined with paracetamol. However, FDA alerts about odeine use in children and it should be used with careful monitoring only in patients from which benefits outweigh the risks [71]. Another opioid analgesic for treatment of mild to severe dental pain in children is tramadol (1–1.5 mg/ kg). For severe dental pain, the use of morphine (0.2–0.5 mg/kg q4–6 h) is recommended. Other alternatives to morphine are also considered, including fentanyl, hydromorphone, methadone and other opioid agents.

Other approaches to pain treatment of dental pain in children include the use of regional analgesia such as local anesthetic instillation, wound anesthetic infiltration, topical regional analgesia (lignocaine gel), peripheral nerve block and other methods. Dental pain management in children is complex and further improvements are needed to improve the efficacy and safety of pain treatment [72].

#### 5.4. Analgesic use in renal and hepatic insufficiency

Usually this starts with preparing the child and the family in advance, in order to reduce fear and anxiety before intervention and applying patient-controlled analgesia (PCA). In case of major surgical interventions the treatment of predicted pain after treatment in children can

Dental clinicians should assess the pain intensity using the appropriate children pain scale. It is recommended to use the FLACC scale for pain measurement in pediatric patients aged 1 month to 3 years, while for children above 3–7 years the Wong-Baker pain rating scale is used (Figure 1), which has demonstrated to be more sensitive compared to visual analogue scale. For children above 7 years, the Visual Analogue/Numerical Rating Scale is used. A universal measuring tool does not exist but according to a systematic review FACES scale demonstrated to be effective in children from 3 to 12 years in which gradient of emotions cartoons are chosen by children based on their level of pain. There is also another measurement, such as Oucher pain scale, which does not differ much from the others, but it is more specific in different racial face expressions such as Caucasian, African American, Hispanic, First Nations Boy and Girl

Multimodal and multiapproach therapy is the cornerstone of pain management in children. This technique uses different analgesia and nonpharmacological complementary approach in order to enhance the pain control and minimize drug-induced adverse effects. This method supports the use of combined nonopioid (NSAIDS, other analgesic agents, local anesthetics, alpha2-adrenergic agonists, voltage-gated calcium channel alpha-2 delta-proteins) and opioid analgesics and other agents in smaller doses in order to prevent the clinical manifestations of drugs side effects [70]. Dosage calculations of analgesics for children are based on mg/kg body weight administered by intravenous, oral and rectal route, while intramuscular injections should be avoided. It is recommended that severe pain is treated by infusions, PCA and other

Figure 1. Wong-Baker faces pain rating scale explains to the person that each face is for a person who has no pain (hurt),

some, or a lot of pain by asking the person to choose that best describes how much pain he has.

Pain treatment options in neonates and premature infants should avoid the use of opioid analgesics. However, in cases when there is no other option, opioid analgesics should be closely monitored in intensive care units. In this group of infants, opioids are more prone to

continue with oral analgesics depending on patient needs.

and Asian Boy and Girl [64–69].

122 Pain Relief - From Analgesics to Alternative Therapies

routes of continuous analgesic administration.

develop dependency and depression of cardiorespiratory functions.

There is an increased risk for renal dysfunction in patients undergoing analgesic treatment, although moderate use is not associated with increased risk of renal disease or dysfunction [73]. Patients with renal failure should be carefully considered due to the increased risk of side effects in dental treatment and also when analgesic therapy is indicated. This requires consultation with the nephrologists or hepatologists for the grade of the disease and an important monitoring for clinical parameters which need to be observed. Regarding medication, dose adjustments need to be considered as an important step to reduce side effects or toxicity. For NSAIDs dose reduction or avoidance is also indicated in more advanced stages of renal failure. In aspirin, acetaminophen and ibuprofen treatment indications prolongation of dosing interval is recommended; however, dose reduction is recommended for diclofenac and naproxen. When the GFR is <10 mL/min avoidance need to be considered, excluding acetaminophen in intervals of 8–12 h. On the other side narcotic analgesics (morphine, fentanyl, codeine) are metabolized by the liver and usually do not require dose adjustment [74, 75]. But special caution should also be exercised in patients with end-stage renal disease without dialysis whereby the use of opioids such as codeine, dihydrocodeine, dextropropocyphene and hydrocodone is not recommended (tramadol may be used with caution). Also, only short-term treatment must be prescribed for morphine, diamorphine, or dose reduction in fentanyl by 25–50% or methadone 50–70% with specialist advice on prescribing and special care in the elderly due to highly variable pharmacokinetics [76, 77].

Due to pharmacokinetic changes in the elderly and reduced renal and metabolism capacity, acetaminophen is the drug of choice for the control of mild to moderate pain in doses of 500– 1000 mg every 4 h. Moreover the overuse of this drug is related with side effects including acute liver failure, hepatotoxicity and in rare cases nephrotoxicity. Taking this into consideration, chronic dosing needs to be avoided in patients with decreased liver function or cirrhosis [78, 79]. In cirrhotic patients, NSAIDs should be avoided or used with extreme caution due to increased risk of gastrointestinal bleeding and risk of hepatotoxicity or acute hepatic decompensation or risk of renal failure.

For opioids, low dose of tramadol is considered as second choice in this group of patients after acetaminophen [80].

Opioid side effects are more common in hepatic impairment due to prolongation of their effects. Conversely, fentanyl and methadone pharmacokinetic is less affected by hepatic impairment. Fentanyl is recommended more than methadone. And also hydromorphone, morphine and oxicodone are other choices that are recommended with caution [81]. Consultation with specialist and also titration should be done slowly, monitoring of drug concentrations and adverse effects are crucial steps in the use of analgesics in dental management for patients with impairment of renal or hepatic functions (Table 2).



Table 2. Use of analgesic drugs in dentistry in special populations.

Due to pharmacokinetic changes in the elderly and reduced renal and metabolism capacity, acetaminophen is the drug of choice for the control of mild to moderate pain in doses of 500– 1000 mg every 4 h. Moreover the overuse of this drug is related with side effects including acute liver failure, hepatotoxicity and in rare cases nephrotoxicity. Taking this into consideration, chronic dosing needs to be avoided in patients with decreased liver function or cirrhosis [78, 79]. In cirrhotic patients, NSAIDs should be avoided or used with extreme caution due to increased risk of gastrointestinal bleeding and risk of hepatotoxicity or acute hepatic decom-

For opioids, low dose of tramadol is considered as second choice in this group of patients after

Opioid side effects are more common in hepatic impairment due to prolongation of their effects. Conversely, fentanyl and methadone pharmacokinetic is less affected by hepatic impairment. Fentanyl is recommended more than methadone. And also hydromorphone, morphine and oxicodone are other choices that are recommended with caution [81]. Consultation with specialist and also titration should be done slowly, monitoring of drug concentrations and adverse effects are crucial steps in the use of analgesics in dental management for

> 500–1000 mg every 8 h (maximum 3 g)(reduce maximum dose 50– 70% for adults with reduced hepatic function or alcohol

> Lowest effective dose for the shortest Possible time (It is recommended to use NSAIDss with PPIs to avoid gastrointestinal bleeding, or use celecoxib in patients with no significant risk factors for cardiovascular events)

Oxycodone 2.5 mg every 6 h Hydrocodone 5 mg every 6 h Tramadol 25 mg daily with increase every 2–3 days with 25

10–15 mg/kg every 4–6h5–7 mg/ kg every 8–12 h 5–10 mg/kg every

0.5–1 mg/kg every 4–6 h

mg up to 100 mg. (It recommended 25–50% dose reduction from recommended dosage in adults and shortest

possible time)

8–12 h

Gastric ulceration-bleeding; Abdominal pain; Hepatotoxicity and acute liver failure; Acute renal failure; Allergy; Skin, Rashes; Urticaria, Cardiovascular-

Myrocardial infection, atherothrombosis, Chronic heart failure; Ischemic Stroke; More sensitive for opioids induced side effects. More pronounced drug interaction associated adverse

Acetaminophen hepatotoxicity in liver disorders Gastric irritation, ulceration, bleeding and perforation and clotting impairment from NSAIDs Codeine associated nausea, sedation, constipation, dependency.

effects.

patients with impairment of renal or hepatic functions (Table 2).

Population Analgesic drug Dosing Adverse effects

abusers)

pensation or risk of renal failure.

124 Pain Relief - From Analgesics to Alternative Therapies

Elderly Acetaminophen (First choice in mild to moderate pain)

Celecoxib)

Opioids (Oxycodone, Hydrocodone, Tramadol) (moderate to severe pain)

Children Acetaminophen Ibuprofen (age 2– 12) Naproxen (age 2–12)

risks)

Codeine/Acetaminophen (3 days or less and only with careful monitoring and only in patients which benefits outweighs the

NSAIDs (Ibuprofen, Naproxen, Flurbiprofen, Ketorolac,

acetaminophen [80].
