Predicting Postoperative Pain: A Complex Interplay of Multiple Factors

See Article, p 656 The management of postoperative pain is of considerable interest to both the patient and the health care team in the perioperative period, especially in the setting of the current opioid epidemic. It is known that a relatively large number of patients undergoing surgery will go on to develop chronic postoperative pain (CPP), defined as pain lasting greater than 3 months after surgery.1 The incidence of CPP varies by surgery type and maybe 30%–85% following amputation, 30%–50% following coronary bypass, 5%–63% following inguinal herniotomy, and 13%–44% following knee arthroplasty.2 It is also known that inadequate postoperative pain control is associated with higher postoperative pain scores and increases the likelihood of developing CPP.3 It is, therefore, important to effectively manage postoperative pain to increase patient comfort and satisfaction, while at the same time, reducing the likelihood of the patient developing chronic pain. On the other hand, it is also imperative to appropriately manage postoperative pain with the minimal opioid dose necessary for adequate pain control to reduce both the side effects from these medications and to also decrease the long-term need for chronic postoperative opioid therapy. In fact, prolonged opioid use after surgery (POUS), which can be defined as having filled ≥1 opioid prescription in the 90–180 days after surgery, is common and affects patients who undergo a variety of procedures. One large recent study evaluating POUS incidence in opioid-naive patients who underwent common hand surgery procedures in the United States showed a rate of 13%.4 The key is to predict who may benefit from more aggressive perioperative pain management regimens, including a focused preoperative evaluation and testing, taking into consideration both patient and surgery characteristics. In the prospective observational study by Luedi et al,5 the authors address the important topic of predicting postoperative pain in patients undergoing short-stay anorectal surgery. In this study, the authors subjected 128 patients to preoperative pressure pain threshold (PPT) testing to obtain a baseline measure of pain perception or tolerance by the patient. To measure the PPT, an algometer with a 0.5-cm2 rubber tip was applied to the subject’s skin and continuously increased until the pressure was felt by the patient to reach a visual analog scale (VAS) of 3. The tests were performed during the surgery clinic visit before the operation. PPT is 1 form of quantitative sensory testing (QST), which is a diagnostic tool that can be used to measure sensory thresholds for pain, pressure, vibration, and hot and cold temperature sensations. When used for pain perception, the application of a noxious stimulus followed by an assessment of pain allows one to measure pain perception of the entire afferent pathway, from the periphery to the brain. We know from extensive prior literature that QST has been shown to be reliable and reproducible.6 In addition to pressure thresholds, other forms of QST to generate pain thresholds include electrical and thermal testing of both heat-pain and cold-pain thresholds. It is important to note that 1 disadvantage of QST is that this tool is a psychophysical test and is, therefore, subject to patient-dependent factors, such as patient motivation and interest in sincere participation, which can significantly alter the results of each study. The individual performing the PPT must also be properly trained so that the test is administered in a consistent way to each patient. In this study, after PPT testing of the 128 subjects, the authors followed them through the perioperative period, obtaining pain scores at postoperative days (POD) 1, 3, and also at 4 weeks. They also analyzed postoperative analgesic medication consumption as a secondary outcome. The authors found that patients with lower preoperative PPT tended to have higher postoperative pain scores on POD 3 and at 4 weeks but not on POD 1. Thus, the authors concluded that there is a direct correlation between preoperative PPT testing and postoperative pain VAS scores. In addition, there appears to be an association between PPT and the need for additional analgesics. However, only 11 patients in this study required additional analgesics, and it is, therefore, unclear, based on these data, if PPT testing can be used to predict postoperative opioid consumption in this surgical population. This, however, was not the primary aim of the study, and additional research is needed to understand whether PPT testing can predict analgesic requirements and a need for long-term opioid use. Given their results, the authors concluded that PPT testing might serve as an aid in identifying patients at risk for developing worse postoperative pain. It is important to point out a few important limitations of this study. One notable drawback is that the study was done at a single facility, which predisposes it to institution-specific surgical and anesthetic techniques. In addition, the data were restricted to a specific surgical population (ie, anal fissure, anal fistula, anal vein thrombosis, condyloma, hemorrhoids, pilonidal sinus disease, rectal prolapse) and generally younger patients. The study hospital is also specialized for performing these procedures and likely has more streamlined management of these patients. Hence, study findings may not be generalizable to average hospitals performing lower numbers of these specific procedures. The study also excluded patients with chronic pain and underlying psychiatric disease, the conditions that are known to impact postoperative pain. In addition, all patients received general anesthesia, but an unknown number received pudendal nerve blocks, which would certainly confound the measuring of postoperative pain scores. Another limitation is more related to PPT test implementation itself. Although a single operator (ie, a surgeon) did the PPT testing for this study and testing was done according to manufacturer’s guidance, as with many measurement tools, operator- and patient-dependent factors may influence the results of the pressure testing. Practical considerations for implementation of preoperative PPT testing include the timeliness of performing this test. Compared to other factors that help predict postoperative pain, such as demographic and surgery-specific indicators, this modality may be time consuming to implement. The idea of “personalized” pain management based on the factors associated with the specific case is intriguing and more research is needed to create tools for clinicians that accurately predict who will experience increased pain or require additional analgesics, and even who is at risk of developing maladaptive behaviors, including chronic pain and opioid-use disorder. Extensive research in this area has already identified a variety of factors that may contribute to postoperative pain, including demographic, surgical, and psychological factors, along with measures obtained from experimental pain testing and genetic profiling.7–9 The demographic factors that are thought to contribute to higher postoperative pain scores include both younger and older age, and possibly female sex, although the data are conflicting on the latter. Independent surgical factors, such as the type of surgery (ie, thoracic, orthopedic), emergent versus elective, and duration of surgery, may all contribute to increased postoperative pain scores. In addition, psychological factors, such as anxiety, depression, tobacco use, substance abuse disorders, as well as preoperative pain and additional risk factors obtained via validated surveys (ie, pain catastrophizing scale), have been shown to be associated with increased pain in the postoperative period. The Table shows known factors that may impact postoperative pain, with specific examples and other considerations. Table. - Factors That May Impact Postoperative Pain Risk Factor Special Considerations Patient demographics Younger or older age+/− female sex Surgical Thoracic surgery Orthopedic surgery Limb amputation Emergent versus elective Preoperative pain High preoperative pain scores Chronic pain conditions Preoperative opioid use Psychological Anxiety/stress Depression Substance abuse Catastrophizing Pain perception Increased sensitivity to experimental pain: quantitative sensory testing of pressure, thermal, electrical thresholds Increased temporal summation Genetic Genetic factors affecting pain sensitivity CYP4502D6 enzyme SNP A118G in OPRM1 receptor polymorphisms Genetic factors are also likely to play a role in the development of postoperative pain, including a genetic predisposition to increased pain levels and genetic variations in opioid receptor sensitivity and opioid metabolism. For example, genetic variations in the catecholamine-O-methyltransferase (COMT) gene may alter pain sensitivity, and research into the single nucleotide polymorphism A118G in the OPRM1 gene shows an association with reduced sensitivity to opioids with a respective decrease in opioid efficacy and inadequate pain relief.10 It is also widely known that mutations in the cytochrome P450 CYP2D6 enzyme, with enzyme activity ranging from poor metabolizer to ultrarapid metabolizer, can lead to either overdose or undertreatment with certain opioid and nonopioid medications.11,12 Due to the multifactorial nature of pain perception in any given patient for any given surgery, no 1 factor has been identified that can accurately predict postoperative pain scores. Furthermore, although we do have current guidelines to aid in perioperative pain management regimens, such as those for enhanced recovery pathways,13–15 those should be supplemented with more specific, evidence-based guidance that can help more accurately “predict” the intensity of postoperative pain and the need for analgesics. It is, however, in our interest to continue to generate data that can be used to risk stratify patients coming to the operating room. Continued research in this area will aid in the development of tiers of predictive risk factors for increased postoperative pain that may allow us to guide which patients need which risk assessment screening tools. This will allow for the development of pain management protocols that can be used to target patients who are at high risk of having worse postoperative pain. In fact, future research may lead to a postoperative pain predictor algorithm and even a pain “calculator,” whereby standard guidelines can be created based on available data to suggest which patients may benefit from more advanced and/or time-consuming preoperative screening, such as psychosocial surveys, QST, or even genetic testing. In summary, the study by Luedi et al5 provides further evidence that tools exist to aid us in predicting who may have higher postoperative pain scores and, therefore, assist us in providing a more individualized approach to perioperative pain management. This should result in improved patient care, decreased postoperative pain, increased patient satisfaction, reduced postoperative opioid consumption and related side effects, while decreasing the risk of developing chronic postsurgical pain. DISCLOSURES Name: Ehren R. Nelson MD. Contribution: This author helped analyze and interpret the data, draft the initial manuscript, and critically revise the manuscript. Conflicts of Interest: E. R. Nelson received consulting fees from BioTras. Name: Tong J. Gan, MD, MBA, MHS, FRCA. Contribution: This author helped analyze and interpret the data, draft the initial manuscript, and critically revise the manuscript. Conflicts of Interest: T. J. Gan received consulting fees from Edwards, Heron, Medtronic, Merck, and Acacia. Name: Richard D. Urman, MD, MBA. Contribution: This author helped analyze and interpret the data, draft the initial manuscript, and critically revise the manuscript. Conflicts of Interest: R. D. Urman received funding for unrelated research by National Science Foundation, Agency for Health Research and Quality, Medtronic, Merck, AcelRx, and received consulting fees from Takeda, Heron, Sandoz, Acacia. This manuscript was handled by: Honorio T. Benzon, MD.