Chronic Pain as an Outcome of Surgery

ONE potential adverse outcome from surgery is chronic pain. Analysis of predictive and pathologic factors is important to develop rational strategies to prevent this problem. Additionally, the natural history of patients with and without persistent pain after surgery provides an opportunity to improve the understanding of the physiology and psychology of chronic pain.Ideally, studies of chronic postoperative pain should include (1) sufficient preoperative data (assessment of pain, physiologic and psychologic risk factors for chronic pain); (2) detailed descriptions of the operative approaches used (location and length of incisions, handling of nerves and muscles); (3) the intensity and character of acute postoperative pain and its management; and (4) follow-up at intervals to 1 yr or more. In addition, there would be information about postoperative interventions that may influence pain, such as radiation therapy or chemotherapy. At long-term follow-up visits, patient function, physical signs, and symptoms would be evaluated using a standardized algorithm, including quantitative and descriptive pain assessments. We found no studies that contain all of these data.For this review, we specifically sought population data that reflect the incidence of chronic postoperative pain or predictors (medical, physiologic, and psychologic) of chronic pain. We selected five groups of surgeries (limb amputations, breast surgery, gallbladder surgery, lung surgery, and inguinal hernia surgery). These surgeries were selected because the incidence of pain is known to be high, thus improving the probability of detecting predictive factors. They also represent a range of major surgical procedures.We performed a computerized search of the medical literature using the OVID search engine (OVID Technologies, Wolters Kluwer, Amsterdam, The Netherlands). The search was performed on the entire database in January 1999 and covered 1966 through most of 1998. Additional articles published during the review process have also been included. Terms were used in their “exploded” format. The term “pain” was combined with the other appropriate term (e.g., “cholecystectomy”); also the text words associated with the pain syndromes were searched, resulting in more than 1,700 citations. Letters to the editor were not reviewed. Additionally, articles known to the authors but not found in the search were used. If the article contained data about persistent pain (12 weeks or more after surgery), it was considered for inclusion in this review. To calculate the incidence of pain, we used the number of individuals responding at the time the chronic pain data was gathered, and only used data from articles in which the methods section indicated that there was systematic collection of long-term pain information from patients. Studies of fewer than 50 patients were excluded in the incidence data analysis for breast surgery, gallbladder surgery, and lung surgery. Studies of fewer than 100 patients were excluded from the data analysis for inguinal hernia surgery. Amputation studies of 25 subjects or more were included because of the higher incidence of chronic pain.The reported incidence of phantom limb pain varies from 30 to 81% (table 1). Finch et al . 1reported pain in 30% of 57 long-term survivors of amputation for vascular insufficiency. Fisher and Hanspal 2described 93 consecutive amputees referred to a prosthetic rehabilitation clinic; therefore, selection bias may be a factor. The remainder of the studies (table 1) report an incidence of phantom limb pain of more than 50%. Sherman et al. 3noted at least a 78% incidence of phantom limb pain, and perhaps as high as 85%; however, their questionnaire response rate was not high (55%). Stump pain was noted in 66% of patients with phantom pain and in half of those without phantom pain; therefore, the overall stump pain incidence exceeds 60%. Wartan et al . 4reported a 62% incidence of phantom limb pain and 63% for stump pain. Similar to Sherman et al., 66% of patients with phantom limb pain also have stump pain. Smith and Thompson 5reported that pain was more common after amputation for cancer than for trauma, but this study was a chart review (phantom pain noted in medical record), and there were only eight amputations for trauma. No large studies systematically evaluate the incidence of phantom limb pain after trauma, vascular disease, and cancer-related surgeries. The presence of intense preoperative pain in the extremity increases the probability of phantom limb pain (from 33 to 72% at 3 months). 6,7Some early reports 8,9indicated that the incidence of phantom limb pain decreased with prolonged (72 h) preoperative epidural pain control, followed by postoperative epidural pain control. Both studies were small (23 and 24 patients, respectively at 6 months follow-up), and neither was properly randomized. In a subsequent randomized controlled study, 10this observation was not confirmed, but preoperative pain control was limited to 18 h, and the extent and intensity of perioperative blockade was not sufficient to control pain without supplemental systemic opioids.The effect of anesthesia (epidural, spinal, or general) alone has not been studied. Surgical handling of the major nerves is rarely mentioned, so we cannot assess the effect of nerve ligation or clipping versus section alone.Administration of chemotherapy increases the incidence of phantom limb pain. 5Stump pain at 1 week is significantly associated with phantom pain at 1 week, 6and long-term stump pain predicts long-term phantom limb pain. 3There is also a correlation between nonpainful phantom sensations and phantom pain. 4Control of acute postoperative pain with nerve sheath infusion of local anesthetic decreased the incidence of phantom limb pain in one series of 11 patients, 11but a subsequent randomized controlled trial (n = 14 at long term follow-up) 12failed to confirm this finding. Both of these studies are small, and the negative study 12does not have the statistical power to conclude that there is no significant effect. There has also been a negative retrospective report of this technique (n = 21). 13As mentioned previously, data regarding epidural analgesia 8–10as a method to decrease the incidence of phantom limb pain conflict.Most authorities believe that phantom limb sensation and phantom limb pain are central phenomena and explain them using the neuromatrix theory expounded by Melzack. 14,15That is, there is a matrix in the central nervous system for the perception of a body part, and this matrix exists even when the body part does not. Sherman et al . 3emphasized that multiple etiologies may lead to phantom limb pain, based on the inconsistency of therapeutic responses.The incidence of phantom limb pain decreases during the first year after amputation, as does the frequency of painful episodes 7,16; however, about half the individuals with long-term phantom pain report no decrease in the intensity of this pain. 3Phantom limb pain is common after extremity amputation, and documented predictors of this pain include preamputation pain and persistent stump pain (acute and chronic). No conclusive studies have evaluated the effect of acute or subacute stump pain control on long-term stump pain or on long-term phantom limb pain. Also no psychologic studies have evaluated patients before amputation for predictors of chronic pain.Long-term pain after thoracotomy, the postthoracotomy pain syndrome (PTPS), may have an incidence of more than 50%. 17,18Six studies met our inclusion–exclusion criteria (table 2), assessing 878 patients, of whom 417 (47%) had PTPS. Katz et al . 2could not predict PTPS from preoperative psychologic testing (state or trait anxiety, depression inventory) or preoperative pain sensitivity as determined by pressure algometry. This study (n = 23) was the extension of a previous acute pain study; it therefore lacks statistical power and may be subject to selection bias. Perttunen et al . 19noted the presence of preoperative pain in 17% of their patients but did not analyze it as an independent risk factor.Several recent case series report that video-assisted thoracoscopic lung surgery (VATS) is associated with a low incidence of PTPS. Walker et al . 20reported only 1 case of 83 (1.2%), and Mouroux et al . 21noted a 3% incidence of PTPS, but neither group reports systematically looking for PTPS. In a large retrospective survey, Landreneau et al . 22(table 2) noted a lower incidence of pain in patients who had VATS compared with those who underwent lateral thoracotomy (30 vs. 44%); however, pain medication requirements did not differ. The difference in pain incidence was statistically significant only during the first year after surgery. In a small (n = 30), nonrandomized prospective study, Furrer et al. 23found a 36% incidence of PTPS in patients undergoing VATS wedge resection, and a 33% incidence of PTPS in a matched group of patients undergoing lobectomy by a classic posterolateral thoracotomy. However, the results are confounded because the thoracotomy group received thoracic epidural analgesia with local anesthetic and opioid, whereas the thoracoscopic group received intravenous patient-controlled opioids. Nomori et al. 24retrospectively and Benedetti et al. 25prospectively (case series) reported a decreased severity of chronic pain after anterolateral thoracotomy when compared with classic posterolateral thoracotomy (mean visual analog scale VAS score, 6 of 100 vs. 21 of 100). Both studies were small (24 and 42 patients), and chronic postoperative pain was not a primary outcome parameter. In descriptions of the surgical technique for posterolateral thoracotomy, details about whether a rib was resected or about how the intercostal nerves were handled were missing from most reports.A recent report by Obata et al . 26(table 2) found a significant effect of intraoperative plus postoperative epidural analgesia when compared with just postoperative epidural analgesia (decreasing the incidence of pain at 6 months from 67% to 33%). This is a prospective, randomized, single-blind study.The intensity of acute postoperative pain is a statistically significant predictor 18,27of PTPS (36 vs. 56% PTPS for minor vs. moderate to severe acute pain). As mentioned previously herein, the combination of intraoperative plus postoperative epidural analgesia with local anesthetic was associated with a decreased incidence of pain at 6 months. An attempt at preemptive analgesia 28had not improved analgesia on long-term follow-up. 18Another small study found that the type of postoperative analgesia affected the incidence of pain at 12 weeks (less pain with epidural analgesia or intercostal nerve cryoablation), but data of only 33 subjects divided among four treatment regimens were reported. 29Benedetti et al. 25,30showed that intercostal nerve dysfunction (loss of the superficial abdominal reflex) is associated with more acute, subacute, and chronic (3 months) pain. Of 23 patients with intact reflexes on postoperative day 1, none had pain at 2 to 3 months, whereas 50% of individuals with persistent loss of the reflex still had pain at this time.The etiology of PTPS may depend on nerve damage because it is more severe after chest wall resection, 31–33and the loss of superficial abdominal reflexes is associated with an increased probability of PTPS. 25,30Another contributing factor is recurrence of tumor. 31For thoracoscopic surgeries and posterolateral thoracotomy, Landreneau et al . 22noted a 30% decrease in the incidence in pain reported by patients more than 12 months after surgery compared with those 3–12 months after surgery. The prospective study by Perttunen et al . 19noted the incidence of pain at 3, 6, and 12 months to be decreasing (80, 75, and 61%, respectively). Of patients with long-term pain after thoracotomy, up to half describe their pain as moderate or severe, 18and 66% are prescribed analgesics for the pain. 27Postthoracotomy pain syndrome is common. The predictors of this syndrome (when tumor recurrence is excluded) include the extent of acute postoperative pain and intercostal nerve dysfunction (which may link more acute pain and persistent pain). One prospective, randomized controlled study 28found that the combination of intraoperative plus postoperative thoracic epidural analgesia decreases the incidence of PTPS at 6 months.Table 3summarizes various studies of pain after breast surgery. Women who undergo breast surgery experience chest wall, breast, or scar pain (range, 11–57%), phantom breast pain (13–24%), and arm and shoulder pain (12–51%). The incidence of pain in one or more of these sites is close to 50% 1 yr after breast surgery for cancer. The postmastectomy pain syndrome (PMPS) has recently been reviewed, 34with some disagreement about which pains to include in this syndrome. Husted et al . 35documented that, of 163 women who had undergone mastectomy with axillary node dissection, 45% reported cicatrix pain, 45% reported arm, neck, or shoulder pain, and only 21% were symptom free (symptoms included pain, paresthesia, lymphedema, and impaired shoulder function) 1–5 yr after surgery. Moderate to severe pain was reported by 16 patients (10%). Krøner et al . 36reported a significant relation between preoperative breast pain and postoperative phantom breast pain in a prospective study of 120 patients. In contrast, Tasmuth et al., 37,38in a prospective study of 93 patients, did not find the presence of preoperative pain to be a predictive but only patients had pain before surgery. depression and were more common in patients in whom chronic pain when compared with those in whom chronic pain did not statistical was not type of surgery may the incidence of pain. Tasmuth et al. that chronic pain was more common after breast surgery than after surgery in their large retrospective study, but did not confirm this in prospective et al., their questionnaire of women who had undergone breast surgery, found that mastectomy combined with of a breast a higher incidence of pain than did mastectomy alone et al . in the of the nerve at 3 months after axillary node in of women in whom the nerve was and in of women in whom it was et al . that axillary increased the of arm and of psychologic et al . found the extent of axillary with the incidence of arm pain and et al . a analysis of factors that the patient to chronic pain after breast cancer surgery. The extent of acute postoperative pain and the number of of postoperative analgesics were the predictors of persistent pain in the breast and the Additionally, postoperative radiation therapy was a risk factor for chronic pain in the breast and the et al . that axillary radiation therapy increased the incidence of arm pain and et al . Krøner et al . a relation between phantom breast sensations and radiation but their studies were and only sought a of of the pain after breast surgery has been to nerve whether from surgery or and that and sensation decreased nerve in the long-term in of women undergoing and of women undergoing but pain data were not reported. was in the of the nerve in of women undergoing axillary In in of women with these was associated with a higher incidence of arm pain and arm symptoms and were more common after breast surgery with axillary node The among pain, and preoperative psychologic have not been among women undergoing breast natural history of pain during the first year after surgery has not been In one study, the incidence of pain in the breast decreased from to from 3 weeks to 1 yr after surgery, whereas the incidence of decreased from to study, the incidence of arm pain decreased from 3 to months after surgery to respectively). incidence of phantom breast pain is from 3 weeks to 6 pain is common after breast surgery, and the major predictive factors are the extent of acute postoperative pain, the presence of pain before surgery, the type of surgery, nerve radiation and preoperative or abdominal pain after is common (range, but than the preoperative incidence of pain The syndrome has a number of in to abdominal pain, and may not have a factors include postoperative pain; pain by postoperative of pain by a other than gallbladder pain by a and other preoperative factors that the patient to an is a predictor of long-term pain and symptoms after other risk factors include symptoms before surgery. history of classic gallbladder symptoms is associated with risk of chronic pain and surgical to no significant difference in overall et al., a randomized controlled trial (n = noted that patients randomized to had more to whereas patients randomized to had more of scar pain and did not report pain incidence There to be no difference in chronic abdominal pain when is compared with et al . a 30% incidence of abdominal pain more than 1 yr after but this incidence did not include 16 patients with pain. et al . significantly more pain after than after surgery and that there was more intercostal nerve damage from the et al., a prospective study of 100 patients who underwent noted that pain at 6 weeks was a predictor of persistent pain and other symptoms at 1 yr and We found no studies that evaluated acute postoperative pain as a predictor of chronic are multiple etiologies of the including of and scar pain. The of factor has not been the frequency of persistent symptoms after patient after the is high, with authors that may to patient most patients with abdominal pain and believe that without surgery and that their improve after symptoms are common after as is chronic abdominal pain. factors include psychologic preoperative symptoms and pain at 6 weeks after surgery. studies of the syndrome have not scar pain and pain from other of chronic pain and number of studies have evaluated chronic pain after surgery, with the reported incidence of chronic pain from to (table The overall incidence from these studies is of pain was a primary outcome in only four these studies report a In a prospective study of surgery for a hernia had a higher incidence of moderate to severe pain at 12 months than did surgery for a primary for have a higher pain incidence at 6 months than those who are for by of vs. 1 of have had pain for a of time before data are about whether the surgical the incidence of chronic pain. et al., a prospective randomized controlled study that evaluated recurrence found a lower incidence of chronic pain after a when compared with an The study found a significantly lower incidence of pain at 12 months after a compared with an et al. no difference in the incidence of chronic pain in their prospective randomized controlled study that compared an to a and no difference in the incidence of pain in their case with and a incidence of chronic pain. of the studies that including pain, were more common early in their experience with hernia a prospective study, et al. not find statistically significant in chronic pain after or in a prospective analysis of et al., no significant in chronic pain between and in primary hernia surgery. the experience of the or the of is a factor in chronic pain or recurrence has been incidence of chronic pain in case series data from hernia is reports with higher of chronic pain from are no prospective studies of this extent of pain at 1 and weeks after surgery is a predictive factor pain at 1 length of type of the incidence of chronic pain. relation between postoperative dysfunction and chronic pain the that nerve damage is a pathologic factor. authors the pain is of the of the et al . the incidence of moderate to severe pain decreased from at weeks to at 1 Moderate to severe pain at 1 and weeks was the predictor of pain at 1 pain after hernia surgery is not but it to be common than chronic pain after the surgeries previously hernia surgery is a large number of individuals are affected by chronic pain. dysfunction has been to be a as has the intensity of early postoperative pain. The of acute pain therapy on the incidence of chronic pain is patient with surgical results is reported to be high, studies reported that chronic pain is common after these and this has been in a recent review. pain is to in of and and the of chronic pain after surgery should be is also there is significant in the incidence of chronic pain among these surgical for inguinal hernia and thoracic surgery). We believe that our review has been but the of search our search did not all articles known to the authors that to the or incidence of chronic pain after the selected surgeries. for this include in not included in the at the time of (e.g., et al . and or “pain” not as a or used in the or (e.g., et al. As a we are not that we all articles that contain data to this a number of risk factors for prolonged pain after surgery and these factors (1) preoperative (2) intraoperative and (3) postoperative factors (table pain is a predictor of chronic pain for pain, breast pain, abdominal pain and symptoms after of these the of the preoperative pain that chronic pain to be pain of 1 or more in is a risk factor for persistent pain after has not been evaluated in the other surgeries has also been found to predict outcome after surgery. damage is an intraoperative factor that to chronic postoperative pain. undergoing thoracotomy are to have intercostal nerve dysfunction and to have PTPS. breast surgery, is associated with damage of that and to the nerve are associated with a lower incidence of pain. nerve damage does not pain because the incidence of decreased sensation was higher than the incidence of pain in the of the nerve after axillary node Benedetti et al. chronic pain in only 50% of individuals with intercostal nerve dysfunction after thoracotomy. nerve dysfunction to be associated with chronic pain. most predictive postoperative factor is the severity of acute postoperative pain after breast surgery, surgery, hernia radiation therapy increases the risk of chronic pain after breast surgery, chemotherapy increases the risk of phantom limb pain. acute pain chronic pain has been a that and factors and the severity of acute pain as factors in the of chronic pain. we believe that from nerve increases acute pain and early months) chronic pain. in the nervous system associated with acute pain, with the that pain should be considered a of the nervous not a symptom of some other If persistent pain after surgery results from may be be Obata et al . this in thoracotomy patients with intraoperative plus postoperative epidural but other studies of preemptive analgesia are from factors are also predictors of chronic pain. Of the surgical we reviewed, the only psychologic predictor has been The questionnaire for psychologic a that with depression are preoperative predictors of chronic pain after surgery. et al . when to predict chronic pain in acute pain patients. They that is not associated with an increased risk of of chronic low pain, but may reflect or in that are to chronic pain. The of et al. with the psychologic in chronic pain is common after amputation, inguinal hernia surgery, breast surgery, gallbladder surgery, and lung surgery, and this is also in recent review. of these data may be as chronic pain as one of acute postoperative pain is a predictor of chronic pain. studies should the factors of in the from acute to chronic pain. may in more and more rational early We that, in some patients, the type of nerve may explain the in acute pain and the chronic pain, but the extent of pain be by other psychologic and physiologic factors that pain