Version May 2024
INTRODUCTION — Chronic pain (defined as pain that persists for more than three to six months) is one of the most common reasons that patients seek medical attention, and affects more than 20 percent of children and adults in the United States alone [1]. Chronic pain begins as acute pain, with surgery being a common cause of acute pain.
This topic will discuss prevalence and risk factors for development of chronic pain after surgery, what is known about mechanisms of the development of chronic pain, and possible strategies for prevention. Whereas this topic focuses on chronic pain after surgery, much of the information is applicable to the transition of other types of acute pain to chronic.
Persistent pain after some specific types of surgery is discussed in more depth separately.
●(See "Clinical manifestations and diagnosis of postmastectomy pain syndrome".)
●(See "Post-herniorrhaphy groin pain".)
●(See "Lower extremity amputation", section on 'Phantom limb pain'.)
●(See "Upper extremity amputation", section on 'Phantom limb pain'.)
Management of chronic pain including chronic postsurgical pain (CPSP) is discussed in detail separately. (See "Approach to the management of chronic non-cancer pain in adults".)
Management of acute pain in adults and children is discussed separately. (See "Approach to the management of acute pain in adults" and "Approach to the management of acute perioperative pain in infants and children".)
DEFINITIONS — Chronic postsurgical pain (CPSP) is also referred to as chronic postoperative pain, persistent postoperative pain, or persistent postsurgical pain. The definition of CPSP varies in the literature, and may refer to pain that lasts at least 3, 6, or 12 months after a surgery.
Relevant definitions from the International Association for the Study of Pain (IASP) are as follows [2]:
●Chronic pain is defined as that which lasts longer than three to six months, or beyond the duration required for normal tissue healing after an acutely painful event, and not explained by either pre-existing pain conditions, or complications such as infection or malignancy.
●In the IASP’s new chronic pain taxonomy for International Classification of Diseases 11th Revision (ICD-11), chronic pain after surgery is defined as pain that develops or increases in intensity after surgery or a tissue injury and persists beyond three months, without other causes [2].
●CPSP is localized to the surgical field or area of injury, projected to the innervation territory of a nerve situated in this area or referred to a dermatome (after nerve damage) or Head’s zone (after surgery to deep somatic and visceral tissues) [2].
Separate from the IASP definition, pain may also be categorized as postsurgical if it occurs outside the main surgical field but is directly related to the procedure, (eg, at the site of graft harvesting, the site of line insertion, or from positioning of the patient).
CLINICAL PRESENTATION AND EVALUATION — Normally, acute postsurgical pain resolves as the inflammation produced by surgery dissipates and the tissues heal. This usually takes days to weeks, although multiple postoperative pain trajectories have been described [3]. (See "Approach to the management of acute pain in adults", section on 'Pain trajectories'.)
There is not a uniform presentation for patients who go on to develop chronic postsurgical pain (CPSP). However, CPSP typically begins as difficult-to-control acute postoperative pain that responds poorly to opioids, often with neuropathic features (eg, burning, tingling or pins and needles, shooting or electric shock, allodynia or hyperalgesia). This is consistent with the high risk of CPSP after surgery associated with nerve damage (eg, limb amputation, breast surgery, thoracotomy, inguinal hernia repair) [4]. Neuropathic features are less common in patients with CPSP after hip or knee arthroplasty. (See 'Risk related to surgery' below.)
The progression from acute to CPSP may be non-linear, with a dynamical ebb and flow of the pain experience across time and settings often seen; some patients have a relatively pain free hiatus after acute pain, followed by recurrence of pain [5].
When evaluating a patient with persistent pain after surgery, one goal is to exclude other diagnoses and determine whether there is a treatable cause for the pain, progression of disease (eg, recurrent malignancy), or a surgical complication (eg, hardware failure after spine surgery). Diagnostic imaging and laboratory testing may be required to confirm the diagnosis.
Further evaluation and management of chronic pain are discussed in detail separately. (See "Evaluation of chronic non-cancer pain in adults" and "Approach to the management of chronic non-cancer pain in adults" and "Pharmacologic management of chronic non-cancer pain in adults".)
MECHANISMS OF TRANSITION TO ACUTE TO CHRONIC PAIN AFTER SURGERY — The mechanisms involved in the chronification of acute pain are complex and not fully understood. Neurobiological, psychosocial, and genetic factors are thought to be important. In addition, chronification of acute postoperative pain may be the result of the surgery, which can lead to nerve injury, infection, scar formation, or altered biomechanics.
Neurobiological mechanisms — Neuroplasticity in the central nervous system appears to be a key feature in the development of chronic pain after acute pain [6]. Neuroplasticity refers to the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury [7]. Surgical incision and tissue trauma results in varying degrees of nociceptive, inflammatory, and neuropathic processes in the periphery, each of which may activate pain pathways in the spinal cord and supraspinal circuits in the amygdala and thalamus [8], and lead to central sensitization [9]. Multiple neurotransmitters and inflammatory mediators are involved, notably the N-Methyl-D-Aspartate (NMDA) receptor, and are potential targets for prevention and therapy of CPSP (figure 1). (See "Evaluation of chronic non-cancer pain in adults", section on 'Nociplastic pain'.)
Importantly, CPSP may still occur when tissue damage is minimized (eg, by identification and isolating major nerves, or by performing laparoscopic rather than open surgery). This may occur because sensitization of the somatosensory system may occur after even minor injuries [6,10], but the mechanisms do not directly depend upon nociceptive input and/or constant engagement of the ascending and descending pathways.
Genetic factors may explain why some patients develop CPSP and not others. No single genetic cause of chronic pain has been identified, and it is believed to be a complex interaction between multiple genetic factors involving single nucleotide polymorphisms (SNPs) in genes controlling neurotransmitters, metabolism and immune regulation. Some frequently studied and well-documented pain-related SNPs include CAGNG2, COMT, KCNS1, OPRM1, P2RX7, SCN9A (neurotransmission), GCH1 (metabolism), CTSG and IL 10, and IL1R2 (immune response) [11-13]. Going forward, the Acute to Chronic Pain Signatures program (www.a2cps.org) is a multisite observational study that is aiming to characterize the predictive nature of a large suite of biomarkers beyond genes, including proteins, lipids, and metabolites [14,15].
Psychosocial contributors to the transition of acute to chronic pain
Pain is a sensory and emotional experience that is related to, but not reducible to, nociceptive signaling of tissue damage, with psychological, social, and environmental factors contributing. The pain experience is constructed in the brain [8], concurrent with the neurobiologic mechanisms discussed above. Identifying the brain regions which are involved is important for developing pharmacologic, somatic, and psychological therapies. The prefrontal cortex and nucleus accumbens are current foci of interest that have been implicated in maladaptive cognitions that lead to chronic pain such as fear-avoidance and catastrophizing [8]. However, all the regions and how they interact remain to be fully elucidated.
OVERALL INCIDENCE OF CHRONIC POSTSURGICAL PAIN — Chronic postsurgical pain (CPSP) is reported to occur in up to 50 percent of patients after common operations, with severe pain occurring in up to 10 percent [9,16]. The incidence of CPSP may be as high as 80 percent after very high risk surgery (eg, limb amputation). (See 'High risk procedures' below.)
However, the true incidence of CPSP is difficult to determine, and reported rates vary with the type of surgery, the time interval used to define CPSP, and the study population [17,18]. In addition, it can be difficult to determine whether persistent pain is a complication of a successful surgery, or continuation of a pre-existing painful condition for which the surgery was unsuccessful (eg, failed back surgery).
In field testing of the new ICD-11 chronic pain codes, chronic pain after surgery or trauma accounts for approximately 15 percent of cases seen in pain clinics internationally [19].
Examples of studies of the overall incidence of CPSP include the following:
●In a population-based survey study of over 12,000 patients in Norway who had had various types of surgery, CPSP was reported in 40.4 percent of patients; in 22.2 percent the pain was mild (1 to 3/10 on numeric rating scale), moderate (4 to 6 /10) in 11.7 percent, and severe (7 to 10/10) in 6.6 percent [20].
●In a prospective, multicenter registry study including over 12,000 surgical patients in Europe, moderate to severe CPSP (numeric rating scale ≥3) at 12 months occurred in 11.8 percent of patients [16].
Higher rates are reported after some common surgical procedures (eg, breast surgery, inguinal hernia repair, thoracic surgery) and in some patient groups. Incidence related to different types of surgeries is discussed below and is shown in a table. (See 'Risk factors' below.)
RISK FACTORS — There are both surgical and patient-related risk factors for chronic postsurgical pain (CPSP).
Risk related to surgery
Technical considerations — In general, surgical procedures that are more extensive and produce greater tissue damage are associated with increased incidence of CPSP [21-24]. However, studies of the differences in risk of CPSP after minimally invasive surgery versus open surgery are inconsistent, and results may depend on the surgical procedure [25-29].
For some procedures, excision or damage to nerves in the surgical field is associated with increased risk of CPSP that is often neuropathic in nature (eg, axillary nerve during axillary node dissection for breast surgery, ilioinguinal nerve during hernia surgery). However, studies on the intraoperative handling of nerves (ie, identifying nerves deliberately, preserving these nerves, or dissecting them) have produced inconclusive results. (See "Postmastectomy pain syndrome: Risk reduction and management", section on 'Preservation of axillary nerves'.)
Mechanisms for development of CPSP are discussed below. (See 'Neurobiological mechanisms' above.)
High risk procedures — Whereas CPSP occurs after most types of surgery, the following procedures are associated with a particularly high incidence of CPSP (table 1).
●Amputation – Limb amputation is the highest risk procedure for development of CPSP, reported in up to 85 percent of patients [17,30]. CPSP after lower limb amputation may involve residual limb pain or phantom limb pain and is often rated as severe by the patient. Phantom limb pain is most common, occurring in 60 to 80 percent of patients [17,30]. (See "Lower extremity amputation", section on 'Stump pain'.)
Phantom pain can also occur after removal of a breast (33 percent [18]) or the rectum [31]. Risk factors associated with phantom limb pain include preoperative limb pain, diabetes, or depression; lower limb amputation, proximal amputation; postoperative stump pain, concurrent nonpainful phantom sensations, and use of a cosmetic prosthesis rather than a somatosensory feedback prosthesis [17].
●Spine surgery – Persistent pain occurs in as many as 40 percent of patients who undergo spine surgery, with higher rates of persistent pain after fusion and laminectomy compared with discectomy [32]. Potential mechanisms are complex, and may include altered biomechanics resulting in or exacerbation of existing degenerative changes (eg, spondylosis, facet joint arthropathy) and/or nerve compression [33]. Postoperative epidural scarring and other surgical complications (eg, infection, hematomas, hardware failure) can also be contributors. Central sensitization may occur postoperatively or may have developed prior to surgery.
●Thoracotomy – The reported rate of CPSP after thoracotomy varies widely, but may be as high as 80 percent at 3 months and 60 percent at 12 months, with 50 percent of patients having pain severe enough to interfere with daily living [34,35]. Potential mechanisms include damage to the intercostal nerve during incision, retraction or suturing, and/or rib fracture during the procedure. Consistent with possible nerve damage, post thoracotomy pain is often neuropathic in nature. The data are conflicting as to whether videoscopic thoracotomy causes less chronic pain than open thoracotomy [36-39].
●Breast surgery – The incidence of chronic pain after breast surgery varies across studies, with an overall prevalence of 46 percent (95% CI 36-56 percent), and moderate-to-severe in 27 percent (95% CI 10-43 percent) [40]. The pain is often neuropathic in nature. Various syndromes are described including intercostobrachial neuralgia, phantom breast pain, secondary musculoskeletal pains, post-TRAM or DIEP flap pain, reconstruction-related pain (both immediate and from expanders), and pain after revision surgery. Possible mechanisms include operative nerve injury, inflammation, and peripheral and central sensitization. (See "Clinical manifestations and diagnosis of postmastectomy pain syndrome".)
●Hernia repair – Up to 50 percent of patients report residual groin pain at one year after hernia repair, with up to 15 percent reporting moderate to severe or disabling pain. Risk factors, pathogenesis, prevention, diagnosis, and management are discussed separately. (See "Post-herniorrhaphy groin pain".)
●Hysterectomy – The incidence of chronic pain after hysterectomy for benign indications is up to 32 percent [41-43]. Underlying susceptibility to pain may be a more important predictor for CPSP after hysterectomy than surgical nerve damage. [41].
●Arthroplasty – The reported rates of CPSP after arthroplasty vary depending on the definition used. In a 2023 systematic review of the literature, the incidence of CPSP at three to six months after total hip arthroplasty (THA; 16 studies, 9086 patients) was 16.4 percent and after total knee arthroplasty (TKA; 54 studies, 151,869 patients) was 15.6 percent [44]. Persistent or worse pain at 12 months after surgery occurs in as many as 20 percent of patients after hip replacement and up to 33 percent after knee replacement [44-49].
Pain after arthroplasty is high at one month and declines thereafter, remaining significant in a substantial number of patients. As an example, in a single institution prospective study of 116 patients who underwent primary TKA for osteoarthritis, the percentage of patients with VAS >40/100 at 1, 3, 6, and 12 months were 44.4, 22.6, 18.4, and 13.1 percent, respectively [47].
The relatively high risk of CPSP has implications for chronic opioid use. TKA and THA are among the operations associated with the highest risk of long term opioid use. In a retrospective insurance database study of opioid naïve patients who underwent 1 of 11 common surgical procedures, the incidence of chronic opioid use within one year after TKA was 1.4 percent and after THA was 0.6 percent, compared with 0.14 percent of nonsurgical patients [50]. Chronic opioid use was defined as having filled ≥10 prescriptions or >120 day supply of opioids in the first year after surgery, excluding the first 90 days. (See "Risk of long term opioid use and misuse after prescription of opioids for pain", section on 'Type of surgery'.)
Revision surgery is associated with a higher incidence of CPSP than primary arthroplasty [24]. Patient risk factors, particularly the degree of preoperative pain, may be the most important predictors of CPSP after these procedures, rather than surgical factors [51]. (See 'Patient factors' below.)
Anesthetic risk factors — These may include the anesthetic technique (ie, general versus regional), the type of anesthetic agents used (ie, inhalational versus intravenous), the use of opioids, and the management of acute postoperative pain. (See 'Anesthetic management' below.)
Severe acute postoperative pain — Poorly controlled acute postoperative pain may be a risk factor for CPSP. Most, but not all, observational studies have found an association between severe postoperative pain and development of CPSP [52]. However, a causal relationship between severe acute postoperative pain and CPSP has not been proven, and optimal pain control has not been shown to reduce the incidence of CPSP. (See 'Risk reduction' below.)
The presumed underlying mechanism by which severe acute pain may result in neuropathic CPSP is the induction of central sensitization by prolonged flooding of the central nervous system with strong noxious inputs. (See 'Neurobiological mechanisms' above.)
Examples of relevant studies include the following:
●In an international European registry study of over 1000 patients who had 1 of 18 types of elective surgery, the percentage of time the patient experienced severe pain during postoperative day one was a risk factor for developing CPSP at 6 and 12 months [16].
●Similarly, in a meta-analysis of five observational studies of 1387 patients who underwent breast cancer surgery, greater postoperative pain was associated with increased risk of CPSP, with 3 percent more patients experiencing CPSP for each one point increase in acute pain on a 0 to 10 scale [14].
●By contrast, in an international prospective study of 210 patients who underwent breast cancer surgery, postoperative pain score within 72 hours of surgery was not an independent risk factor for CPSP at four months [53].
Patient factors — These include demographics such as age, sex, and marital status; comorbidities including pre-existing pain in the surgical field or remotely (eg, fibromyalgia); and psychosocial factors. Patient factors that have been associated with increased risk of CPSP include the following [54-60] (table 2):
●Younger age
●Female sex (variable association)
●Unmarried status (in females)
●Preoperative pain
●Preoperative anxiety
●Preoperative pain catastrophizing
●Depression
The degree to which these factors increase the risk of CPSP varies among studies of different operations, different study designs, and differing definitions of CPSP. As examples, in one study of 350 patients who underwent inguinal hernia repair, persistent pain occurred in 58 percent of patients <40 years of age, but 14 percent of patients >60 years of age [61]. In a single institution retrospective study of patients who underwent video assisted thoracoscopy, the incidence of CPSP at three months after surgery was 32.2 percent in patients <65 years old, compared with 11.8 percent of patients ≥65 years old [62].
Some of these risk factors appear in predictive tools for specific procedures, as discussed below. (See 'Predicting which patients are at risk of developing persistent pain after surgery' below.)
PREDICTING WHICH PATIENTS ARE AT RISK OF DEVELOPING PERSISTENT PAIN AFTER SURGERY
●Preoperative – For most patients, clinical criteria and risk factors are used to identify patients at risk for developing chronic postsurgical pain (CPSP). They may be identified during the pre-admission clinic visit or screening for pre-existing chronic pain, chronic opioid use, or substance use. Patients who are found during preoperative evaluation to be at risk for pain-related psychological problems can be evaluated with the Pain Catastrophizing Scale [63] and/or the Pain Self-Efficacy questionnaire [64].
●Postoperative – High risk patients may also be identified postoperatively if they have severe acute postsurgical pain, pain with neuropathic features, high postsurgical opioid consumption (>90 MEQ/day), or emotional distress.
Prediction tools — Although risk factors for developing CPSP have been identified, there is no high quality, reliable prediction model that can be used preoperatively. A systematic review of the literature on the quality and performance of CPSP prediction models found the models had many limitations, with only fair predictive performance and high risk of bias and most lacked external validation [65]. Most of the models were developed in patients having only one type of surgery, and included preoperative, intraoperative, and postoperative risk factors.
Prediction tools for specific types of high risk surgery have been developed, though it is unclear how widely they are used [66-71]. As an example, a tool for predicting chronic postmastectomy pain includes five independent risk factors, including two preoperative factors (preoperative pain in the surgical field and obesity), one was intraoperative (axillary node dissection) and two were postoperative (severe pain on day 1 and on day 7) [68]. Unlike many other tools, this one has been validated in test sets and performed well with an accuracy of around 75 percent. An online risk calculator was created to aid scoring.
RISK REDUCTION — Strategies for reducing the risk or preventing chronic postsurgical pain (CPSP) may include preoperative, intraoperative, and postoperative interventions. Other than avoiding surgery, the efficacy of most such interventions is unclear.
Modifying or avoiding surgery — Performing less extensive and/or shorter surgery when possible might decrease the risk of CPSP, since longer and more extensive surgery has been associated with development of CPSP [21-24]. Whether using laparoscopic versus open surgery reduces risk is unclear, and may depend on the procedure. In some cases, surgical technique may be modified to reduce the risk of nerve injury, and is recommended in some guidelines [72,73]. (See 'Technical considerations' above.)
Part of informed discussion prior to surgery should include the risk of CPSP, particularly for high risk surgery and for patients with risk factors for CPSP. Some patients may choose to avoid surgery or to try alternative treatments first.
Anesthetic management
Choice of anesthetic technique — Choice of anesthetic technique (ie, regional versus general anesthesia) and agents for general anesthesia should be based on patient factors and the surgical procedure. The effect of those choices on development of CPSP has not been determined.
●Regional anesthesia versus general anesthesia – There is little literature comparing the effect of using intraoperative regional anesthesia versus general anesthesia on the incidence of CPSP. Most of the relevant literature has evaluated the use of regional anesthesia techniques for postoperative analgesia, as discussed below. (See 'Regional anesthesia techniques for analgesia' below.)
For patients who undergo lower limb amputation, which has a high risk of CPSP and may be amenable to neuraxial anesthesia, the use of neuraxial anesthesia may not reduce the incidence of CPSP. In a retrospective single institution study of 150 patients who had lower extremity amputation, the incidence and severity of stump pain and phantom limb pain at an average of 14 months was similar in patients who had general anesthesia, spinal anesthesia, or epidural anesthesia for the amputation [74].
●Intravenous versus inhalation anesthesia – The effects of the choice of anesthetic agents on the development of CPSP and the underlying mechanisms are areas of active investigation [75]. However, there is insufficient evidence at this time to support the use of a specific type of anesthesia (inhalation versus intravenous) to reduce the risk of CPSP. The existing literature is limited and conflicting.
•In one single-institution randomized trial comparing total intravenous anesthesia (TIVA) with propofol and remifentanil versus inhalational anesthesia using sevoflurane in patients undergoing thoracotomy, the incidence of pain at six months was lower in patients who had TIVA (33.5 versus 50.6 percent) [29]. Similarly, in a retrospective single-institution study of 175 patients who underwent breast cancer surgery, the use of sevoflurane anesthesia was associated with a higher incidence of pain at 12 months compared with propofol anesthesia [76].
•However, remifentanil is associated with opioid induced hyperalgesia, and some studies have found an association between the use of remifentanil and CPSP [77,78].
The use of nitrous oxide during anesthesia may reduce the incidence of CPSP in some specific patients. In a follow-up study of approximately 3000 patients enrolled in the ENIGMA-2 randomized trial of the use of nitrous oxide during major non-cardiac surgery, the incidence of CPSP at 12 months was similar in patients who received nitrous oxide and in those who did not [79]. However, nitrous oxide was associated with reduced risk of CPSP in Asian patients, and patients with methylenetetrahydrofolate reductase gene polymorphisms.
Pre-emptive analgesia — There is little evidence that the institution of pain control methods prior to surgical stimulus reduces the incidence of CPSP [80,81]. A meta-analysis of six small trials of the use of epidural analgesia for thoracotomy (270 patients) found a reduction of CPSP at six months after epidural analgesia started preoperatively compared with postoperative initiation (23 versus 39 percent) [82]. The quality of evidence was low [82]. Similarly, a systematic review of the literature on the use of preoperative analgesia for limb amputation found 11 studies with no strong evidence for reducing CPSP [83]
Postoperative pain control — Although acute postoperative pain is a risk factor for CPSP, effective postoperative pain control does not appear to prevent CPSP [84]. The goal for postoperative pain control should not be total absence of pain, but rather a tolerable level of pain that allows physical and emotional function. There is insufficient evidence to support a recommendation to change this goal for postoperative pain control, specifically to reduce the risk of CPSP [80,81].
Strategies for postoperative pain control are discussed separately. Their effects on CPSP are discussed here. (See "Approach to the management of acute pain in adults".)
Regional anesthesia techniques for analgesia — Regional anesthesia techniques (eg, peripheral nerve blocks, neuraxial analgesia, wound infiltration) are routinely used as part of opioid sparing multimodal analgesia after surgery. However, the role of regional anesthesia techniques in the prevention of CPSP is unclear, and there is a lack of definitive evidence that regional anesthesia techniques prevent CPSP. We use regional anesthesia techniques as part of multimodal postoperative analgesia whenever possible, primarily for improved analgesia and opioid sparing effects, and secondarily, for the possibility that using regional anesthesia might reduce the risk of CPSP. (See "Approach to the management of acute pain in adults", section on 'Regional anesthesia techniques'.)
We use continuous blocks for patients expected to have moderate to severe pain and plan to leave the catheters in for up to five to seven days to maximize analgesia and minimize the need for opioids. As examples, we use continuous popliteal and femoral or adductor canal blocks for below the knee amputation, continuous femoral and sciatic catheters for above the knee amputation, continuous paravertebral for mastectomy, and epidural analgesia for various thoracic and abdominal procedures. Indications and techniques for regional anesthesia are discussed separately. (See "Overview of peripheral nerve blocks" and "Overview of neuraxial anesthesia".)
Regional anesthesia techniques may reduce the risk of CPSP for some types of surgery (eg, breast surgery), though much of the existing literature has methodologic limitations and there is a lack of high quality evidence [85]. For some high-risk procedures (eg, amputation, thoracotomy, arthroplasty), there is little evidence that regional anesthesia techniques reduce the incidence of CPSP.
Preincision initiation of analgesia (regional anesthesia or systemic analgesia) may reduce the incidence of CPSP for some procedures (eg, limb amputation [86], thoracotomy [82], breast surgery [87]), though the quality of available evidence is low.
Examples of relevant studies include the following:
●Various types of surgery – A 2019 meta-analysis included 39 randomized trials that evaluated the effect of local anesthetics or regional anesthesia versus systemic analgesia on the incidence of postsurgical pain at ≥3 months after various types of surgery [88]. Regional anesthesia techniques reduced the incidence of CPSP after thoracotomy (7 trials, 499 patients; odds ratio [OR] 0.52, 95% CI 0.32-0.84), breast surgery (18 trials, 1297 patients; OR 0.43, 95% CI 0.28-0.6), and cesarean delivery (4 trials, 551 patients; OR 0.24, 95% CI 0.08 to 0.69). The quality of evidence was low to moderate. Evidence of other surgeries could not be analyzed due to methodologic problems or too few studies.
●Breast and thoracic surgery – A 2022 meta-analysis of prospective (randomized and observational) and retrospective studies of CPSP after breast or thoracic surgery evaluated the effect of regional anesthesia techniques [59]. For patients who had breast surgery, peripheral nerve blocks as a group did not reduce the incidence of CPSP. When analyzed separately, paravertebral block was associated with reduced incidence of CPSP (6 studies, relative risk 0.65, 95% CI 0.45-0.92). For patients who had thoracic surgery, the incidence of CPSP was similar in those who had regional anesthesia techniques for analgesia (epidural, paravertebral, intercostal, parasternal blocks) compared with those who did not. Conclusions are limited by marked heterogeneity among the included studies.
●Arthroplasty – Randomized and observational studies have not found that regional anesthesia techniques reduce the long term incidence of CPSP after total knee arthroplasty (TKA) [89-91].
●Limb amputation – While epidurals and peripheral nerve blocks can provide excellent acute perioperative analgesia after amputation, there is not definitive evidence that these techniques prevent the development of chronic pain.
•In a meta-analysis of three studies that compared the use of continuous nerve block versus sham block or placebo after lower extremity amputation, the incidence of chronic phantom limb or stump pain was similar in the two groups [92].
•In a small single institution randomized trial of patients with severe preoperative lower limb pain prior to amputation for vascular insufficiency, the incidence of phantom limb pain was lower in patients with well controlled early postoperative pain, and was similar in patients who had epidural analgesia compared with those who had patient controlled intravenous analgesia (PCA) [86].
Studies of preoperative initiation of regional anesthesia techniques for up to several days prior to surgery have produced conflicting results, and most do not suggest a reduction in chronic pain [83,86,93,94].
Analgesics and adjuncts — Whereas several analgesics and adjuncts are used for effective perioperative pain control, the effects of these agents on development of CPSP are uncertain, and we do not routinely administer particular perioperative analgesics in an attempt to prevent CPSP. However, for patients having very major, prolonged surgery we may add methadone and ketamine to assist acute postoperative pain management and in the hope that it may reduce the development of CPSP, even though evidence is lacking. For medications that may be promising, the optimal doses, durations of therapy, and combinations of medications for preventing CPSP have not been determined. The use of these medications (ie, nonsteroidal anti-inflammatory drugs [NSAIDs], gabapentinoids, ketamine, intravenous lidocaine, glucocorticoids) for perioperative pain control, including adverse effects, is discussed in detail separately. (See "Nonopioid pharmacotherapy for acute pain in adults".)
A 2021 systematic review with meta-analyses of randomized trials of adults who underwent elective surgery identified over 100 trials that evaluated the effects of various perioperative drugs on the prevalence of pain at ≥3 months after surgery [80]. There were statistically significant but likely clinically unimportant reductions in CPSP with NSAIDs, pregabalin, and lidocaine at some endpoints. Conclusions are limited by small study size, clinical heterogeneity, and the lack of reported adverse events.
Examples of studies involving commonly used non-opioid analgesics include the following:
●Anti-inflammatory drugs (NSAIDs and glucocorticoids) – The effects of anti-inflammatory agents on the development of CPSP are debated and are of particular interest because of the widespread perioperative use of these drugs. Preclinical and in vitro human studies found that inflammation was associated with reduced transition from acute to chronic pain in patients with back pain or temporomandibular pain, and that reduced inflammation was associated with an increase in development of chronic pain [95].
Consistent with the possible deleterious effect of anti-inflammatories, several small studies in the meta-analysis described above found different effects when NSAIDs were administered for longer periods of time. NSAIDs did not reduce CPSP in studies of mixed surgical procedures [80]. NSAIDs administered for <24 hours after breast surgery (two trials) reduced the prevalence of moderate to severe CPSP at 12 months (risk ratio [RR] 0.26, 95% CI 0.03-2.34), but not when the drug was administered for >24 hours. Meta-analysis of two small trials of breast and spine surgery found that corticosteroids administered for <24 hours increased the risk of moderate to severe CPSP at 12 months compared with placebo (RR 1.47, 95% CI 1.05-2.06).
●Ketamine – Multiple studies have failed to show efficacy of ketamine for reducing the incidence of CPSP. In the meta-analysis described above based on 27 trials involving various surgical procedures, there was no effect of ketamine on the incidence of CPSP regardless of surgical procedure, duration of administration, or the timing of pain evaluation [80].
●Gabapentinoids – Gabapentinoids are first line agents for the treatment of chronic neuropathic pain; CPSP is often neuropathic in nature. However, gabapentinoids administered for acute pain have not been shown to prevent CPSP. In a 2020 meta-analysis of 27 trials (2200 patients) of surgical patients, perioperative administration of pregabalin or gabapentin did not reduce the risk of CPSP at 3 to 12 months after surgery, regardless of the dosing regimen [96].
●IV lidocaine – Perioperative administration of intravenous (IV) lidocaine may reduce CPSP, though the evidence is based on small studies with methodologic problems. Existing studies have evaluated CPSP at three and six months. A meta-analysis of two trials found reduced incidence of any degree of pain at six months after lidocaine administered for <24 hours after breast surgery [80]. Lidocaine did not reduce the incidence of moderate to severe pain at three or six months for any type of surgical procedure.
Psychotherapies — Psychological factors that have been associated with both increased acute pain and development of CPSP are potentially modifiable, and therefore are possible targets for preoperative and postoperative intervention [97]. Psychotherapies (eg, cognitive behavioral therapy, relaxation therapy), where available, should be offered for patients with preoperative anxiety, depression, high surgery related stress, and/or pain catastrophizing. One option for accessing such therapies is to refer the patient preoperatively to a transitional pain service, as discussed below. (See 'Perioperative care coordination and follow up' below.)
Literature on the benefits of perioperative psychotherapy is limited. A meta-analysis of eight randomized trials that assessed the effects of perioperative cognitive behavioral therapy and/or relaxation therapy in patients having various types of surgery found that these therapies modestly reduced the level of pain at 3 to 30 months, compared with usual care (weighted mean difference -1.1, 95% CI -1.9-0.6, on a 0 to 10 scale) [98]. The evidence was judged to be of moderate quality.
The responses of health care professionals to patients’ pain complaints are a modifiable social factor. Clinicians' comments (eg, "never seen a case like yours") and recommendations (order more tests, advice to rest more) can inadvertently increase fear-avoidance and other maladaptive pain coping strategies [99] and should be avoided.
PERIOPERATIVE CARE COORDINATION AND FOLLOW UP — Patients who go on to develop CPSP may be surgically fit-for-discharge but continue to complain of pain and may still be using high doses of opioids and other analgesics. They often have psychosocial factors such as depression, anxiety, and pain catastrophizing that are contributing. There should be coordination among the surgical team, anesthesia and pain services, primary care, and other specialists to plan for perioperative and post discharge care. High risk patients should be seen for follow-up at 6 to 12 weeks after discharge. For patients who continue to complain of pain at 6 to 12 weeks, treatment should be reviewed, and the patient should be referred to their surgeon, primary care provider, and other services as needed (eg, pain clinic, rehabilitation, mental health, addiction medicine).
Transitional pain services are increasingly being developed for care coordination for patients who may be at high risk for difficult to control pain. Patients who are referred to the transitional pain service may be identified preoperatively or after surgery. These programs may include both psychological services and biomedical treatment [100]. Whether such programs reduce the risk of CPSP is unclear. In a retrospective study of 251 patients who were referred to one transitional pain service, opioid consumption and pain at six months after surgery were reduced compared to discharge values, however there was no control group [101]. Mean numeric rating pain score at six months was 4 in preoperatively opioid naïve patients and 5 in opioid experienced patients.
The transitional pain service is discussed separately. (See "Approach to the management of acute pain in adults", section on 'Early preoperative evaluation for some patients'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute pain management" and "Society guideline links: Chronic pain management".)
SUMMARY AND RECOMMENDATIONS
●Clinical presentation – There is not a uniform presentation for patients who go on to develop chronic postsurgical pain (CPSP), though CPSP typically begins with acute pain that is difficult to control, often with neuropathic features (eg, burning, tingling, electric shock, allodynia of hyperalgesia). (See 'Clinical presentation and evaluation' above.)
●Mechanisms of the transition from acute to chronic pain – The mechanisms whereby acute pain becomes chronic may include neurobiologic processes that result in central sensitization, genetic factors, or psychosocial issues. (See 'Mechanisms of transition to acute to chronic pain after surgery' above.)
●Incidence – CPSP may occur in up to 50 percent of patients after various common operations, with severe pain in up to 10 percent. CPSP may occur in up to 80 percent of patients after high risk surgery (eg, limb amputation). (See 'Overall incidence of chronic postsurgical pain' above and 'High risk procedures' above.)
●Risk factors
•Surgical – More extensive surgery and nerve damage during surgery may increase the risk of CPSP. High risk procedures include limb amputation, thoracotomy, breast surgery, hernia repair, benign hysterectomy, and arthroplasty (table 1). (See 'Risk related to surgery' above.)
•Patient – Psychosocial factors (eg, preoperative anxiety, depression, surgery related stress, pain catastrophizing) are associated with increased risk of CPSP (table 2). Genetics may play a role as well. (See 'Patient factors' above.)
•Severe acute postoperative pain – Most observational studies have found that severe acute postoperative pain is associated with development of CPSP, however, causation has not been proven. (See 'Severe acute postoperative pain' above.)
●Risk reduction – Strategies for reducing the risk of CPSP may include preoperative, intraoperative, and postoperative interventions. Other than avoiding surgery, the efficacy of most such interventions is unclear. (See 'Risk reduction' above.)
•Psychotherapies – Psychosocial factors (eg, preoperative anxiety, depression, stress, pain catastrophizing) are potentially modifiable. Where available, psychotherapies (eg, cognitive behavioral therapy, relaxation therapy) may be used for patients with preoperative anxiety, depression, high surgery related stress, and/or pain catastrophizing, though the benefits of psychotherapies in this setting are unclear. (See 'Psychotherapies' above.)
•Modifying or avoiding surgery – For some procedures, performing less invasive surgery (eg, laparoscopic instead of open) or modifying surgical technique to avoid nerve damage may reduce the risk of CPSP, though the supporting literature is not strong. (See 'Modifying or avoiding surgery' above.)
•Anesthetic management
-Whether the choice of anesthetic and/or analgesic techniques affects the incidence of CPSP is unclear, including the use of regional versus general anesthesia, use of regional anesthesia techniques for postoperative analgesia, and the use of nonopioid analgesics and adjuncts (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], ketamine, gabapentinoids, intravenous [IV] lidocaine). (See 'Anesthetic management' above.)
-Poorly controlled acute perioperative pain is associated with increased incidence of CPSP. However, a causal relationship between severe acute postoperative pain and CPSP has not been proven, and optimal pain control has not been shown to reduce the incidence of CPSP. (See 'Severe acute postoperative pain' above.)
-The use of regional anesthesia techniques for postoperative analgesia reduces opioid consumption and improves pain control, but has not been shown to reduce the incidence of CPSP. We use regional anesthesia techniques whenever possible as part of multimodal postoperative pain control, primarily for optimizing analgesia, and secondarily for the possibility of reducing CPSP. For very painful procedures we typically use continuous peripheral nerve blocks or epidural analgesia, and aim to leave the catheters in for at least five days. (See 'Regional anesthesia techniques for analgesia' above and "Approach to the management of acute pain in adults", section on 'Regional anesthesia techniques'.)
●Perioperative care coordination – Patients with ongoing pain at the time of discharge and with psychological factors that increase the risk of CPSP should have postdischarge care coordinated among anesthesia, surgery, and primary care. They should be followed up at 6 to 12 weeks and if necessary, they should be referred for further services (eg, pain clinic, mental health professional, rehabilitation). Where available, patients at high risk for difficult to control pain may be referred to a transitional pain service. (See 'Perioperative care coordination and follow up' above.)
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