Paul Ryan Haffey, Neal Rakesh, Grant Chen, AmitABH Gulati Postthoracotomy pain syndrome (PTPS) is a chronic condition that affects a large percentage of operative patients. One of the most important prevention strategies is ensuring adequate analgesia in the immediate postoperative period. The mechanisms by which the condition develops are not clearly elucidated, but clear risk factors include preexisting pain conditions, age, sex, psychosocial factors, and genetic predisposition. Patients commonly present with complaints of burning, aching, allodynia, and tenderness along the incision site. The importance of a multimodal approach to immediate postoperative pain control cannot be overstated. Pharmacologic and regional anesthesia techniques can also be incorporated into the treatment of PTPS. Neuromodulating medications, nonsteroidal antiinflammatory drugs, opioids, and other pharmacologic medications are commonly used in the treatment of PTPS. Regional anesthesia techniques are also incorporated. PTPS is a complex and poorly understood condition that requires more investigation. postthoracotomy pain syndrome; thoracotomy pain; postoperative pain conditions; pain syndromes According to the International Association for the Study of Pain, chronic postthoracotomy pain is defined as “pain that recurs or persists along a thoracotomy incision at least 2 months following the surgical procedure”.1 The condition may also be referred to as postthoracotomy pain syndrome (PTPS) or postthoracotomy neuralgia. The first cases were described in soldiers after World War II. Patients often describe pain along the thoracotomy scar and a burning, aching sensation that resides along the back or the chest. It may be accompanied by painful dysesthesia or allodynia.2,3 The prevalence of chronic postthoracotomy pain is highly variable, with reports ranging from 33% to 91% in the literature.4,5 One of the most significant predictors of PTPS is inadequate analgesia in the acute postoperative period.2 For this reason effective pain control during this time is critical. Other contributors to the development of PTPS include preexisting pain conditions, age, sex, psychosocial factors, and genetic predisposition. It has been hypothesized that minimally invasive techniques may reduce postoperative pain after any procedure; however, this remains unclear in the case of PTPS.4 The exact mechanisms that lead to PTPS are unclear, and additional investigation is warranted. In addition to surgical approach and genetic contributions, some evidence suggests that intercostal neuroma formation, healing rib fracture, costochondral dislocation, and suprasensitization may all play a role in the development of PTPS.2 Genetic contributions may be important in the development of any type of persistent pain. The exact role that genes play, however, has not been made clear. Some potential genetic influences may arise from the following: genetic polymorphisms of catechol-O-methyltransferase, genetic variants to determine voltage-gated sodium channels, and guanosine triphosphate (GTP) cyclohydrolase.6,7 Additional research into the genetics contributing to the development of many types of persistent painful conditions is needed. Postsurgical nerve injury is a well-described phenomenon in the literature, and it is the most commonly implicated culprit behind the development of PTPS. This is likely because many patients present with distinctly neuropathic symptoms. The patients describe a sensation of burning and numbness along the surgical site, which is typical for neuropathic pain. Some studies have found electrodiagnostic evidence that nerve injury has a causal role in the development of long-lasting postoperative pain after thoracotomy.8 Nerve injury and other factors may also lead to central or peripheral sensitization. Immediately following local injury, a series of inflammatory mediators (i.e., substance P, prostaglandins, adenosine triphosphate, histamine) are released with the aim of attracting immune cells that release cytokines, such as tumor necrosis factor and interleukin-1.9 This inflammatory milieu causes increases in sodium and calcium at the nociceptor nerve terminal thereby generating action potentials leading to the perception of pain. Peripheral sensitization can be characterized by a decreased threshold for activation of this chain of events and may lead to activation of inflammatory mediators without an inciting event such as nerve injury.10 If these pain signals persist, it may lead to a lasting change in the central nervous system that can result in the development of central sensitization. This is a condition in which a patient may experience chronic hypersensitivity and a heightened sensation of pain because of a persistent decreased threshold for activation in the central nervous system.11 The prevention of this unfortunate cascade is just one reason why it is imperative to control pain in the immediate postoperative procedure, particularly in the case of chronic PTPS. Patients often present with pain at or along the incision site, chest tube, or drain site. Some patients also report painful symptoms in the shoulder and, in some cases, diffusely along the T5‒T6 dermatomes.12 It is typically characterized as burning, aching, tender, and sensitive in the area surrounding the scar. Patients also report numbness and additional features characteristic of neuropathic pain including tingling, decreased sensation, and allodynia.13 Between 80% and 90% of patients report pain directly at the surgical site.14 In addition, myofascial pain in adjacent areas (i.e., scapula, neck, shoulder, pectoral musculature) is not uncommon and is likely caused by disruption of the fascial planes during surgery. Some patients also report experiencing sudomotor derangements similar to those experienced in chronic regional pain syndrome. There are some reports that 70% of patients who undergo thoracic surgery may develop PTPS.15 It has been postulated that open thoracic procedures may result in greater incidence of PTPS, but the prevalence of PTPS is roughly equal in both open and video-assisted procedures.13 Based on this information, it is reasonable to conclude that modifications in surgical approach will not have an effect on preventing PTPS. Effective postoperative pain management, however, is essential for the prevention of the development of PTPS. Greater consumption of analgesics during the immediate postoperative period has been associated with a greater incidence of PTPS.16 Therefore using a multimodal protocol to address immediate postoperative pain is essential. This may include a variety of pharmacologic medications including nonsteroidal antiinflammatory drugs (NSAIDs), opioids, neuromodulating medications, and acetaminophen. Preemptive multimodal analgesia may, in fact, prevent hypersensitization of the central nervous system that leads to the development of chronic pain.2,17,18 Incorporating regional anesthesia techniques should also be considered. One highly favored approach includes preoperative NSAIDs, opioid medications, preoperative regional block, and either epidural anesthesia or continuous paravertebral block; this combination was found to result in a lower than average incidence of PTPS.2,17–19 The goal of this technique is to use analgesic therapies with different mechanisms of action to block or modulate different pain pathways, while decreasing the incidence of related adverse effects.20 With this in mind, it is imperative that the clinician take into consideration the patient’s psychosocial history and surgical approach when establishing a pain management regimen with the aim of controlling postoperative pain and taking measures to prevent the development of chronic pain. The utility of preoperative or intraoperative administration of steroids to prevent postoperative pain remains controversial. Studies on the analgesic effects of glucocorticoids have focused primarily on dexamethasone. There have been numerous studies demonstrating the efficacy of a single intraoperative dose, 4 to 8 mg intravenously, in reducing postoperative pain scores and increasing the period to first analgesic request.21 Concerns with its use include raised blood glucose levels and possibly an increased incidence of surgical site infections. However, the latter has been shown to be false by numerous studies.22–24 Nonetheless, in diabetics with poor glycemic control, the intraoperative use of dexamethasone may warrant frequent blood glucose monitoring. Gabapentin and pregabalin are two of the most commonly prescribed neuromodulating medications largely because of their ability to titrate and their reasonably favorable side-effect profile. Similar to many other neuromodulating medications, the mechanism by which these drugs confer pain relief is not completely understood. It is theorized that they work through modulation of voltage-gated calcium channels in the dorsal horn.25 Because many patients suffering from PTPS experience symptoms corresponding with neuropathy, these agents have been especially beneficial.26 Their role in prevention of PTPS, however, has not been fully evaluated. Several studies have looked at the effectiveness of both gabapentin and pregabalin on acute postoperative pain with mixed results. In two studies, the authors found that both gabapentin and pregabalin use reduced opioid consumption and improved pain scores postoperatively.27 In these same studies, pregabalin was also shown to reduce opioid-related side-effects following surgery.28 The optimal dosage was not elucidated in either of these studies and side effects were seen at the doses needed for clinical effect including sedation, dizziness, drowsiness, and visual disturbances. Acetaminophen offers benefits as part of a multimodal analgesic regimen owing to its relative ease of administration, favorable side-effect profile and dependable pharmacokinetics.15 Although the mechanism of action of this medication remains unclear, it appears to exert its effects through the central nervous system providing both analgesic and antipyretic properties, as well as being a weak inhibitor of the cyclooxygenase (COX) enzymes.29 Acetaminophen exhibits a more favorable side-effect profile than NSAIDs, particularly in the postoperative and cancer populations for whom bleeding may be a concern. However, hepatotoxicity is a concern when doses exceed 4000 mg/day in adults or in patients with preexisting liver pathology. As such, caution is advised when used in patients with severe alcoholic liver disease, cirrhosis, or hepatitis. Formulations have been available for both oral and rectal routes of administration for many years and have frequently been used in the perioperative period owing to its low cost. More recently, with the U.S. Food and Drug Administration approval of the intravenous formulation in 2010, the use of acetaminophen for thoracic surgery has increased despite the cost as compared with the other formulations as several studies have demonstrated a benefit in this population of patients. Specifically, studies have shown intravenous acetaminophen to reduce postoperative pain scores and opioid consumption when used as a part of a multimodal analgesic regimen.30 Therefore it is a commonly used perioperative adjunct to a multimodal pain management protocol and may have use in the prevention of PTPS. The utility of acetaminophen in treating PTPS, however, remains unclear; particularly because, much like NSAIDs and COX-2 specific inhibitors, acetaminophen will reach a “ceiling effect” at which point no further benefit will be seen despite increasing concentration of the drug.31 NSAIDs have become more popular for the management of postoperative pain following the advent of parenteral formulations for this class of drugs (i.e., ketorolac). Considerable research has already been devoted to examining their utility in the perioperative period and much of it has shown them to decrease opioid requirements, improve pain scores, and decrease opioid-related side-effects in patients following surgery.32 Much of these same results have also been seen in patients following thoracic surgery. One study was able to show that use of NSAIDs as part of multimodal pain management regimen decreased opioid consumption by about 30% and reduced pain scores by about 60% following thoracotomy.33 Like acetaminophen, however, the utility of NSAIDs in the treatment of PTPS is unclear and most of the research focuses on adequate pain control immediately following surgical intervention. In this capacity, they are likely to be used as a preventative agent. Potential side effects include bleeding, kidney injury, and gastrointestinal mucosal damage. These are of particular concern in the perioperative and cancer populations in whom bleeding risk is increased.
Postthoracotomy Chronic Pain
Abstract
Keywords
Introduction
Pathophysiology
Clinical Presentation
Prevention
Treatment
Gabapentin and Pregabalin
Acetaminophen
Nonsteroidal Antiinflammatory Drugs
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Postthoracotomy Chronic Pain
