**Abstract**

Optimal postoperative pain management presents a challenge for healthcare providers across all surgical specialties, since it is estimated that many patients submitted to major surgeries do not receive an adequate analgesic treatment, increasing the risk of complications, length-of-stay and costs for health assistance. The development of new agents for postoperative pain control creates possibilities for better combinations in preventive and multimodal analgesia. Recently, the use of gabapentinoids (gabapentin and pregabalin) in the perioperative period has become more popular. Several clinical studies and meta-analyses reveal that perioperative gabapentinoids may evoke a significant opioid-sparing effect and probably decrease the postoperative pain score. Gabapentinoids may be a good strategy for preventive and multimodal analgesia in major surgeries, particularly pregabalin, considering its pharmacokinetics profile. Situations where there are limitations of regional anesthesia techniques or in cases where there is an intention to reduce the use of opioids or anti-inflammatory drugs at the trans-operatory period are certainly good opportunities for their use. However, gabapentinoids are associated with several adverse effects, including sedation, dizziness, and peripheral edema. Therefore, further studies are needed to evaluate the real cost-effectiveness of this approach. Additionally, specific attention should be paid to minor and ambulatory surgeries as well as for the elderly patients to which gabapentinoids are clearly not beneficial and potentially harmful.

**Keywords:** Gabapentinoids, Preventive analgesia, Pain, Anesthesia, Gabapentin, Pregabalin

## **1. Introduction**

Pain is one of the most common and significant postoperative events experienced by many surgical patients. Optimal postoperative pain management presents a challenge for healthcare providers across all surgical specialties.

Immediate postsurgical pain affects four out of five patients [1]. In a national US survey of adults who had undergone surgery within the previous 5 years, 86% of overall patients experienced postsurgical pain, and 75% of those who reported pain described its severity as moderate–extreme during the immediate postoperative period [2].

The implications of poorly controlled postoperative pain are substantial, including cardiopulmonary complications, opioid-related side effects, unplanned hospital admissions, prolonged hospital stay, increase in health services costs and the subsequent development of chronic pain or opioid addiction [3]. Additionally, it is noteworthy that when surgeons prescribe more doses of opioids or potent opioids when other non-opioid analgesics may be able to control postoperative pain, they are contributing to the opioid epidemic [4].

Recent evidence has raised the importance of preventive analgesia [5, 6] which may be defined as the occasion where the pharmacological intervention is initiated earlier than the painful stimulus to inhibit nociceptive input before it is triggered. It has been demonstrated that preventive multimodal pain therapy has been successfully implemented for numerous surgical procedures, often resulting in decreased opioid consumption and a shorter hospital stay [7, 8]. Medications to achieve opioid-sparing preventive analgesia include non-steroid anti-inflammatory drugs, magnesium, lidocaine, N-Methyl-D-Aspartate (NMDA) receptor antagonists, glucocorticoids, and alpha2-agonists and some anticonvulsant drugs [9].

Moreover, the prescription of the gabapentinoids (gabapentin and pregabalin) in the perioperative period has become increasingly common and they have become ubiquitous components of protocols for early recovery after surgery and preventive and multimodal analgesia.

Despite the existence of several studies comparing the use of these drugs as preoperative medication for the most diverse surgeries, there are conflicting results and no consensus on what the better choice and ideal dose could be [10]. It is generally accepted that the gabapentinoids are effective in reducing immediate postoperative pain and opioid consumption. However, it is noteworthy that the patients' safety has emerged as a broader gabapentinoids concern once these drugs have significant adverse effects as well.

Further definition of uncommon side effects, the optimal preoperative and postoperative doses, treatment duration, and dosage schedule are needed before perioperative gabapentinoids can be broadly recommended as the standard of care for all patients.

Therefore, this book chapter will present a systematic review of literature regarding the pharmacological and relevant clinical features about gabapentinoids for preventive analgesia, including the used drugs with their respective doses, routes of administration, tolerability, and safety profile as well as procedure-related complications and patients' satisfaction.

#### **2. Pain control**

The International Association for the Study of Pain (IASP) has stated in 1979 that pain is a distressing experience associated with actual or potential tissue damage with sensory, emotional, cognitive, and social components [11, 12]. Therefore, it is known that the painful experience involves the interpretation of the biological aspects of pain, but also its interaction with the social and cultural characteristics of everyone [13].

Pain plays an important role in biological signaling as a necessary condition for our survival, evoking autonomic, pathological, and psychological responses to prevent tissue damage and it can be classified as acute or chronic pain [14].

#### *Gabapentinoids in Preventive Analgesia: Pharmacological and Clinical Aspects DOI: http://dx.doi.org/10.5772/intechopen.98900*

The acute condition has a burden beginning, limited duration and it is associated with a local well-established and self-limited cause, with a time course usually lower than 3 months. On the other hand, the chronic pain may be considered a disease state, since it may be understood as the pain that outlasts the normal time of healing (higher than 3 months) and it may arise from psychological states, it serves no biological purpose, and has no recognizable endpoint [15].

Considering its pathophysiology, pain may be classified as nociceptive, neuropathic, or mixed pain. The neuropathic pain is associated with damage to the somatosensory nervous system. On the other hand, the most common is the nociceptive or inflammatory pain which comes from any tissue other than the neurological one. It happens after different types of stimuli, such as physical, mechanical, chemical, infectious and others, which promotes pain and regeneration of the injured tissue. The post-operative pain as well as those related to trauma and ischemic conditions are known as nociceptive pain [16].

The human body has a physiological protection system that acts as a neural network for the perception of harmful stimuli [17]. Briefly, pain processing starts with the information transduction that occurs when peripheral nociceptors are activated and detect a damage or harmful stimulation from the environment, transforming it into an action potential to inform the central nervous system (CNS) of homeostasis alteration. After that, information transmission by free and specialized nerve endings (known as A-delta and C fibers) occurs and the stimulus is carried out to the CNS through afferent pathways crossing the spinal medulla, arriving at the cerebral cortex where pain perception occurs.

Fortunately, the human body has a descending inhibitory system for acting on pain modulation. Central structures located at the brain, hypothalamus, brainstem, and dorsal horn of the spinal cord release mediators such as serotonin, norepinephrine, gamma aminobutyric acid (GABA) and acetylcholine to inhibit the algic stimuli [14].

Pain is a classic problem related to major surgeries, and its inadequate control occurs in a significant number of patients predisposing dissatisfaction and failure to ambulate, resulting in a longer hospitalization, with higher risk of morbidity and mortality [18]. Therefore, the knowledge of pain physiology is essential to understand the mood of action of many medications used in anaesthesiology, including preventive and multimodal analgesia.
