Risk Of Chronic Postsurgical Pain Research Articles

Frontiers in Chronic Pain: Nonpharmacologic Presurgical Management to Reduce the Risk of Chronic Postsurgical Pain—Part 1

Dr. Film is Associate Professor, Department of Physical Therapy and Rehabilitation Science, University of Maryland School of Medicine, 100 Penn St, 315B, Baltimore, MD 21201; E-mail: [email protected]. The purpose of this article is to review options to predict, assess, and manage postoperative pain. The author, faculty, and staff in a position to control the content of this CME/NCPD activity, and their spouses/life partners (if any), have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations relevant to this educational activity. CME Accreditation Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation assessment survey on the enclosed form, answering at least 70% of the quiz questions correctly. This CME activity expires on December 31, 2022. NCPD Accreditation Lippincott Professional Development is accredited as a provider of nursing continuing professional development (NCPD) by the American Nurses Credentialing Center's Commission on Accreditation. Lippincott Professional Development will award 2.0 contact hours for this continuing nursing education activity. Instructions for earning ANCC contact hours are included on page 11 of the newsletter. This NCPD activity expires on December 2, 2022.

A randomized controlled TRIal of cognitive BEhavioral therapy for high Catastrophizing in patients undergoing lumbar fusion surgery: the TRIBECA study

BackgroundAround 20% of patients undergoing spinal fusion surgery have persistent back or leg pain despite surgery. Pain catastrophizing is the strongest psychological predictor for chronic postsurgical pain. Psychological variables are modifiable and could be target for intervention. However, randomized controlled trials evaluating the effectiveness of psychological interventions to reduce chronic pain and disability after spinal fusion in a population of patients with high preoperative pain catastrophizing scores are missing. The aim of our study is to examine whether an intervention targeting pain catastrophizing mitigates the risk of chronic postsurgical pain and disability. Our primary hypothesis is that targeted perioperative cognitive behavioral therapy decreases the risk of chronic postsurgical pain and disability after spinal fusion surgery in high catastrophizing patients.MethodsWe will perform a two-center prospective, single-blind, randomized, controlled study comparing lumbar spinal fusion surgery outcome between 2 cohorts. Adult patients selected for lumbar spinal fusion with decompression surgery and a minimum score of 24 on the pain catastrophizing scale will be randomized with 1:1 allocation for either perioperative cognitive behavioral therapy (intervention group) or a perioperative education plus progressive exercise program (control group). Patients randomized to the intervention group will receive six individual sessions of cognitive behavioral therapy, two sessions before the operation and four after. Primary outcome is the Core Outcome Measures Index at 12 months. Secondary outcomes include pain, disability, depression and quality of life.DiscussionThis is the first trial that evaluates the effectiveness of cognitive behavioral therapy as a perioperative tool to improve pain and disability after spinal fusion surgery in comparison with an educational/exercise control intervention, in patients with high levels of pain catastrophizing. If perioperative cognitive behavioral therapy proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcome after spinal fusion surgery.Trial registrationClinicaltrials (NCT03969602). Registered 31 May 2019,

Postoperative Pain Management in Pediatric Spinal Fusion Surgery for Idiopathic Scoliosis.

This article reviews and summarizes current evidence and knowledge gaps regarding postoperative analgesia after pediatric posterior spine fusion for adolescent idiopathic scoliosis, a common procedure that results in severe acute postoperative pain. Inadequate analgesia may delay recovery, cause patient dissatisfaction, and increase chronic pain risk. Despite significant adverse effects, opioids are the analgesic mainstay after scoliosis surgery. However, growing emphasis on opioid minimization and enhanced recovery has increased adoption of multimodal analgesia (MMA) regimens. While opioid adverse effects remain a concern, MMA protocols must also consider risks and benefits of adjunct medications. We discuss use of opioids via different administration routes and elaborate on the effect of MMA components on opioid/pain and recovery outcomes including upcoming regional analgesia. We also discuss risk for prolonged opioid use after surgery and chronic post-surgical pain risk in this population. Evidence supports use of neuraxial opioids at safe doses, low-dose ketorolac, and methadone for postoperative analgesia. There may be a role for low-dose ketamine in those who are opioid-tolerant or have chronic pain, but the evidence for preoperative gabapentinoids and intravenous lidocaine is currently insufficient. There is a need for further studies to evaluate pediatric-specific optimal MMA dosing regimens after scoliosis surgery. Questions remain regarding how best to prevent acute opioid tolerance, opioid-induced hyperalgesia, and chronic postsurgical pain. We anticipate that this timely update will enable clinicians to develop efficient pain regimens and provide impetus for future research to optimize recovery outcomes after spine fusion.

Presurgical risk model for chronic postsurgical pain based on 6 clinical predictors: a prospective external validation.

No externally validated presurgical risk score for chronic postsurgical pain (CPSP) is currently available. We tested the generalizability of a six-factor risk model for CPSP developed from a prospective cohort of 2929 patients in 4 surgical settings. Seventeen centers enrolled 1225 patients scheduled for inguinal hernia repair, hysterectomy (vaginal or abdominal), or thoracotomy. The 6 clinical predictors were surgical procedure, younger age, physical health (Short Form Health Survey-12), mental health (Short Form Health Survey-12), preoperative pain in the surgical field, and preoperative pain in another area. Chronic postsurgical pain was confirmed by physical examination at 4 months. The model's discrimination (c-statistic), calibration, and diagnostic accuracy (sensitivity, specificity, and positive and negative likelihood ratios) were calculated to assess geographic and temporal transportability in the full cohort and 2 subsamples (historical and new centers). The full data set after exclusions and losses included 1088 patients; 20.6% had developed CPSP at 4 months. The c-statistics (95% confidence interval) were similar in the full validation sample and the 2 subsamples: 0.69 (0.65-0.73), 0.69 (0.63-0.74), and 0.68 (0.63-0.74), respectively. Calibration was good (slope b and intercept close to 1 and 0, respectively, and nonsignificance in the Hosmer-Lemeshow goodness-of-fit test). The validated model based on 6 clinical factors reliably identifies risk for CPSP risk in about 70% of patients undergoing the surgeries studied, allowing surgeons and anesthesiologists to plan and initiate risk-reduction strategies in routine practice and researchers to screen for risk when randomizing patients in trials.

Risk and protective factors for chronic pain following inguinal hernia repair: a retrospective study.

A large proportion of patients experience chronic post-surgical pain (CPSP) following inguinal hernia repair surgery. The aim of this study was to investigate the predictive risk factors and protective factors for CPSP following inguinal hernia surgery. After institutional ethics approval was obtained, we conducted a retrospective observational case-control study including a total of 236 adult patients undergoing electiveinguinal hernia repair at a single tertiary medical center from 2014 to 2015. Preoperative and postoperative variables were collected from electronic medical records. Binary logistic analysis was used to determine the association between CPSP and clinical factors and built a CPSP risk model. The incidence of CPSP was 14.4%. Bilateral inguinal hernia repair (OR 4.44; 95% CI 1.62 to 12.17; p = 0.004), preoperative pain (OR 2.57; 95% CI 1.14 to 5.79; p = 0.023), preoperative anxiety (OR 1.05; 95% CI 1.01 to 1.09; p = 0.018), and relatively high intensity of acute pain at 1week after the surgery (OR 1.40; 95% CI 1.03 to 1.91; p = 0.031) were the risk factors for CPSP while low-dose ketamine at anesthesia induction (OR 0.42; 95% CI 0.18 to 0.98; p = 0.044) was the protective factor for CPSP in patients undergoing inguinal hernia repair. These results indicated that bilateral inguinal hernia repair, preoperative pain, preoperative anxiety, and acute pain at 1week after the surgery were the independent risk factors for CPSP while low-dose ketamine was the protective factor. These findings may assist with primary prevention by allowing clinicians to screen for individuals with the risk of CPSP.

An investigation of the effect of patient-controlled analgesia on long-term quality of life after major surgery: A prospective cohort study.

Chronic pain is a common postoperative complication in patients undergoing major surgery and may significantly affect their quality of life (QOL). Whether patient-controlled analgesia (PCA) can reduce the risk of chronic postsurgical pain and promote long-term QOL is still unclear. In this prospective cohort study, we followed up patients undergoing major surgery, recorded changes in their postoperative QOL over time using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and chronic pain events, evaluated the long-term effects of distinct PCA techniques (intravenous, epidural, or none) on their QOL and risk of chronic pain, and explored relevant predictors. The patients' QOL and chronic pain events were collected preoperatively, 3, 6, and 12 months after surgery. Generalized linear mixed models were used to control for individual heterogeneity and adjust for potential confounding factors. We included 328 patients undergoing major surgery from September 22, 2015, to December 31, 2016, in this study. Multivariate regression models showed that patients using intravenous PCA had a better QOL in physical health (adjusted coefficient 3.7, 95% CI, 0.5-8.0) compared with those receiving non-PCA treatments. Distinct PCA techniques did not significantly affect QOL in psychological, social relationship, or environmental domains of the WHOQOL-BREF scale or the risk of chronic postsurgical pain. Patients using intravenous PCA had a better QOL in physical health over time after major surgery, which may have been due to factors other than pain-relieving effects.

Review of the Transitional Pain Service as a method of postoperative opioid weaning and a service aimed at minimizing the risk of chronic post-surgical pain.

Opioid use and prescribing have become a subject of increasing focus and scrutiny. The ongoing "opioid epidemic" in North America has further increased interest in this area. In patients presenting for surgery, the prescribing of opioids during and following admission to hospital is commonplace and has been identified as a potential contributor to the growing opioid problem in North America. This review aims to present the timeline of the "opioid epidemic" as well as to introduce the concept of a "Transitional Pain Service". The Transitional Pain Service is a multidisciplinary service originating at Toronto General Hospital that employs a multi-faceted approach to monitoring opioid use after discharge from surgery, and aims to safely wean patients from opioids while maintaining effective pain management. This approach and its results will be discussed in this review.

Transition from Acute to Chronic Pain: Evaluating Risk for Chronic Postsurgical Pain

Background: The pathophysiology of pain involves complex nervous system interactions after initial noxious stimuli. When stimuli persist, biochemical and structural changes occur in the nociceptive pathways of the central and peripheral nervous systems, leading to pain sensitization. Peripheral and central sensitization are key in the transition from acute to chronic pain. This development of chronic pain is particularly common following various surgical procedures, with many postsurgical patients experiencing persistent pain for significant periods. Chronic pain is a common and severe complication of surgery, and preventing its development is tantamount in improving patient outcomes. Objectives: To understand underlying pathophysiology of chronic postsurgical pain (CPSP) and the underlying risk factors predisposing the transition from acute to CPSP. To review our ability to identify patients at highest risk for the development CPSP. To identify evidence-based multimodal approaches that can aid in the prevention of CPSP. Study Design: Narrative review of peer-reviewed literature. Setting: Inpatient surgical centers. Methods: Medline and Cochrane databases were reviewed to identify publications relevant to CPSP pathophysiology, risk factors, predictive models, and prevention. Publications were selected based on author expertise to summarize our current understanding of CPSP. Results: This review presents our current understanding of CPSP in the following domains: underlying pathophysiology, predisposing risk factors, predictive models of CPSP, and preventative strategies. Each section provides a structured review of key evidence base to understand the complex topic of CPSP. Limitations: This narrative review is a nonsystematic review of relevant publications aimed at presenting succinct overview of CPSP. Conclusions: The incidence of CPSP can potentially be reduced through early identification of perioperative, genetic, physiologic, and psychologic factors. Models predicting the development of CPSP continue to improve and may help focus preventative efforts in patients at highest risk. There is a growing body of evidence supporting the use of multimodal analgesia and anesthetic techniques in the reducing rates of CPSP development. Key words: Acute pain, chronic postsurgical pain, pain sensitization, chronic pain prevention, regional anesthesia, pain adjuncts, neuraxial anesthesia, chronic pain risk factors

Correlation between CCL2, CALCA, and CX3CL1 gene polymorphisms and chronic pain after cesarean section in Chinese Han women: A case control study.

Objective:Postoperative chronic pain is characterized by high incidence, long duration, and complex pathogenesis. The purpose of this study was to investigate the correlation between the single nucleotide polymorphisms of the CCL2 gene rs4586 (g.5974T>C), CALCA rs3781719 (−692T>C), CX3CL1 rs614230 (2342C>T), and the risk of postoperative chronic pain in Chinese Han women.Methods:We analyzed the CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 single nucleotide polymorphism (SNPs) of 350 Chinese Han women with chronic postsurgical pain (CPSP) 6 months after cesarean section and 350 healthy women without chronic pain (HC). The levels of CCL2, CALCA, and CX3CL1 in serum were detected by enzyme-linked immunosorbent assay (ELISA).Results:The CCL2 rs4586 T allele and the CX3CL1 gene rs614230C allele were protective factors for CPSP risk (adjusted OR = 0.766, 95% CI: 0.675–0.865 and OR = 0.336, 95% CI: 0.644–0.835). The CALCA gene rs3781719C allele was a risk factor for CPSP (adjusted OR = 1.273, 95% CI: 1.125–1.424). CCL2 rs4586, CX3CL1 gene rs614230, and CALCA gene rs3781719 locus gene polymorphisms were associated with serum CCL2, CX3CL1, and CALCA protein levels.Conclusion:Our results support that CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 gene polymorphism are associated with the occurrence of chronic pain after cesarean section in Chinese Han women.

Genetic polymorphisms and prediction of chronic post-surgical pain after hysterectomy-a subgroup analysis of a multicenter cohort study.

Chronic post-surgical pain (CPSP) is a serious problem. Clinical and psychological variables have not been able to explain all observed variance in prevalence and severity of CPSP. The first objective is to determine the association between genetic polymorphisms and the prevalence of CPSP after hysterectomy. The second objective is to analyze if the implementation of genetic polymorphisms into a previously performed clinical and psychological predictor analysis on the development of CPSP after hysterectomy will improve its discriminatory power. A prospective multicenter cohort study was performed in patients undergoing hysterectomy for benign indication. Clinical and psychological variables were collected by questionnaires in the week before surgery, post-operatively up to day 4, 3 and 12 months after hysterectomy. Blood was collected and 16 polymorphisms previously suggested to be correlated to CPSP (COMT, GCH1, KCNS1, CACNG2, and OPRM1) were genotyped. Logistic regression analyses were performed. Three hundred and forty-five patients were available for the genetic analyses. The prevalence of CPSP 3 months post-operatively was 10.5% and after 12 months 7.9%. The polymorphism rs4818 within the COMT gene was associated with the prevalence of CPSP after 3 months. No polymorphisms were associated with CPSP after 12 months. The addition of rs4818 to the prediction model did not change its discriminatory power significantly. The rs4818 polymorphism within the COMT gene was associated with the prevalence of CPSP 3 months after hysterectomy, but the implementation of rs4818 into the prediction model did not significantly improve the chance of identifying hysterectomy patients at risk for CPSP.

Chronic pain following laparoscopic living-donor nephrectomy: Prevalence and impact on quality of life.

Chronic postsurgical pain (CPSP) following laparoscopic donor nephrectomy (LDN) is a disregarded topic. In this cross‐sectional study, all consecutive patients who underwent an LDN at the Radboud University Medical Center (Radboudumc; 2003‐2016) were approached for participation. Five hundred twelve living kidney donors were included and asked to complete two questionnaires, including the McGill Pain Questionnaire and the RAND Short Form‐36 Health Status Inventory (RAND SF‐36) regarding their health‐related quality of life (HRQoL). The mean prevalence of CPSP following LDN was 5.7%, with a mean follow‐up time of 6 years. Possible predictors of CPSP following LDN are severe early postoperative pain, previous abdominal surgery, and preexisting backache. The RAND SF‐36 revealed an impaired HRQoL in patients with CPSP when compared to patients without CPSP. In conclusion, this study revealed that the prevalence of CPSP following LDN is substantial. Given the possible association between the presence of CPSP and impaired HRQoL scores, living kidney donors should be well informed in the preoperative phase about the risk of CPSP.

Chronic post-surgical pain after colon surgery in patients included in an enhanced recovery program.

Enhanced recovery after surgery (ERAS) program improves immediate recovery. Beyond immediate benefits, long-term impact of ERAS implementation is not yet evident. This retrospective single-center cohort study investigates prevalence and characteristics of chronic post-surgical pain (CPSP) in patients who underwent colon surgery. Two hundred and ninety-seven patients enrolled prospectively in our ERAS database were contacted by mail to question the presence of CPSP. In case of CPSP, intensity, location, and type of pain, impact of pain on quality of life and treatment taken were assessed. Post-operative pain experience during hospital stay, recall of pain, and discomfort duration when back home were assessed in all patients. Comparison between patients with and without CPSP was made to approach the risk factors of CPSP in this population. At 27months after colon surgery, 25/198 patients reported CPSP (12.6%) and pain was severe in 5 patients (2.5%). CPSP had a deep abdominal component in 56% of patients and a parietal component in 20% of patients. Patients with CPSP+ differed from patients CPSP- for pre-operative pain presence (56% vs 24.8%, P=0.004), recalled post-operative pain intensity (4 vs 3, P=0.045), duration of discomfort after discharge (2 vs 1weeks, P=0.035). Pre-operative pain was found as a significant CPSP risk factor (odds ratio 1.34; 95% CI: 1.05-1.70). CPSP prevalence after laparoscopic colon surgery seems not much affected by ERAS context. Pre-operative presence of pain emerged as an important risk factor. These findings should be confirmed in a prospective multicenter study.

(363) Antidepressant Use in Patients with a History of Depression is Associated with Reduced Opioid Use after Total Knee Arthroplasty

Chronic post-surgical pain (CPSP) affects up to 40% of patients and is associated with prolonged postoperative opioid use. Depression is one risk factor for CPSP, but it is unknown if antidepressants modulate the risk for CPSP or prolonged postoperative opioid use in patients undergoing procedures at high-risk for CPSP. This retrospective cohort study utilized the records of Veterans Affairs patients who underwent a total knee arthroplasty (TKA) between April 2012 – April 2016. Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) use was recorded. Exclusion criteria were no depression diagnosis, opioid use preoperatively, other antidepressant use, and chronic pain diagnoses. Outcomes included morphine equivalents through postoperative day one and opioid use through 30, 90, and 365 days after surgery. Generalized linear models were created to adjust for confounding covariates, and a secondary analysis stratified outcomes by antidepressant class. The study cohort included 1,655 TKAs after applying all exclusion criteria, and it was 90.6% male and 77.1% white with a mean age of 65 years. Patients meeting inclusion criteria and using an SSRI or SNRI comprised 454 cases (27.4%). After adjustment for age, BMI, sex, race, general or regional anesthesia, non-opioid adjunct pain medication use, and comorbidities recorded in the VA Surgical Quality Improvement Program (VASQIP), SSRI or SNRI use was associated with reduced opioid use through 30 days after surgery (OR = 0.74 (0.57, 0.95), p = 0.020). In the secondary analysis, SSRI use was associated with reduced opioid use through 90 days after surgery compared to SNRI use (OR = 0.35 (0.14, 0.89), p = 0.022). Perioperative SSRI or SNRI use, in patients with depression, is associated with reduced prescription opioid use 30 days after TKA. Prospective research is warranted to elucidate if there is a role for antidepressants as non-opioid analgesics in specific surgical populations.

The role of multimodal analgesia in preventing the development of chronic postsurgical pain and reducing postoperative opioid use.

Chronic postsurgical pain (CPSP) is a possible complication of various surgical procedures, which can impair patients' quality of life while also contributing to chronic opioid use. Multiple biopsychosocial factors put patients at risk for CPSP. Multimodal analgesia with the use of various pharmacologic and regional anesthetic techniques can help reduce the incidence and severity of CPSP. However, the relationship between various perioperative analgesic strategies and the development of CPSP is not fully understood. Although the use of multimodal analgesia will not automatically prevent CPSP and/or prolonged opioid consumption, there is potential to do so, especially by means of regional techniques.

Comparison of Incidence and Severity of Chronic Postsurgical Pain Following Ear Surgery.

Literature review shows a limited number of studies investigating chronic pain following ear surgeries. The effect of mastoidectomy on chronic postsurgical pain, however, has never been investigated. The present study investigates not only the incidence and severity of chronic pain following ear surgeries with and without mastoidectomy, but also predisposing diseases for pain. The study was performed in a total of 150 patients who underwent tympanoplasty or tympanomastoidectomy through a retroauricular incision in a single tertiary health care center. During the routine postoperative 3rd-month examination, the patients were questioned for the presence and severity of chronic pain, as well as the diseases that might predispose the pain. The difference between the visual analog scale scores of the groups was not statistically significant. Comparison of pain character revealed that neuropathic pain is more prevalent in both the groups. Evaluating the relationship between concomitant diseases and chronic pain, it was observed that migraine, cervical pathology, and acute postsurgical pain were closely associated with chronic pain. It was demonstrated that mastoidectomy does not pose an additional risk for chronic postsurgical pain. However, patients with migraine, cervical pathology, and acute postsurgical pain are at risk for chronic postsurgical pain.

Chronic postsurgical pain and cancer: the catch of surviving the unsurvivable

Chronic postsurgical pain (CPSP) is an important and well recognized cause of much long-term suffering, which in some cases may be preventable and affects many people living with cancer. Unfortunately, general consensus is lacking as to how best reduce the risk of developing CPSP. Cancer is now not always a short-lived, fatal disease and is now moving towards a chronic illness. Poorly managed perioperative pain is the greatest risk factor for CPSP. Recent trials have examined preventive strategies for CPSP associated with breast surgery and thoracotomy, two operations used in cancer treatment. Standard antinociceptive drugs, 5% lidocaine patches and ketamine do not prevent CPSP. The evidence for gabapentinoids is conflicting. Intravenous lidocaine and, separately, regional anaesthesia appear beneficial. Well-managed pain, irrespective of technique, reduces the risk of CPSP. The literature is inconclusive regarding an 'optimal approach.' Regional anaesthesia, intravenous lidocaine and the aggressive management of perioperative pain using multimodal analgesia including antineuropathic pain agents such as gabapentinoids and certain antidepressants are recommended. Clinicians should not rely on general anaesthesia, opioids, NSAIDs and ketamine to prevent CPSP. A blanket approach using gabapentinoids for all patients undergoing major surgery is not indicated. Instead, the presence of perioperative neuropathic pain should be checked for regularly.

Postoperative Pain Trajectories and Pain Chronification-an Empirical Typology of Pain Patients.

High intensity of acute postsurgical pain is one of the strongest predictors of chronic postsurgical pain (CPSP). We investigated if different types of patients with distinct combinations of initial pain intensity and rate of pain resolution exhibit different risks for increased pain intensity six months after surgery. Data from 174 patients were examined using growth mixture analysis by means of structural equation modeling. Three types of patients were distinguished on the basis of acute pain trajectories. The majority of patients (57%) showed an unproblematic pattern of little initial pain on the first postoperative day, combined with further pain resolution over the four subsequent days. There also was a substantial group of patients (30%) who started out with severe pain but exhibited a high rate of pain resolution. Finally, we found a problematic group of patients (13%) who reported high pain intensities throughout all five postoperative measurements, with no signs of pain resolution. Even after controlling for preoperative pain intensity, these patients exhibited significantly higher pain intensities six months after surgery than the remaining patient groups. In this study, we demonstrated that there is substantial variation in postsurgical pain trajectories, not only with regard to postsurgical initial pain intensity, but also with regard to individual rates of pain resolution. Successful pain resolution appeared to be a better predictor of absence of increased pain intensities six months after surgery than initial pain immediately after surgery. Hence, attention should be given to appropriate pain treatment in order to minimize the risk of CPSP.

Should thoracic paravertebral blocks be used to prevent chronic postsurgical pain after breast cancer surgery? A systematic analysis of evidence in light of IMMPACT recommendations.

The role of thoracic paravertebral block (PVB) in preventing chronic postsurgical pain (CPSP) after breast cancer surgery (BCS) has gained interest, but existing evidence is conflicting, and its methodological quality is unclear. This meta-analysis evaluates efficacy of PVB, compared with Control group, in preventing CPSP after BCS, in light of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. Electronic databases were searched for randomized trials comparing PVB with Control group for CPSP prevention after BCS. Eligible trials were assessed for adherence to IMMPACT recommendations. The primary outcomes were CPSP at 3 and 6 months, whereas secondary outcomes were PVB-related complications. Data were pooled and analyzed using random-effects modelling. Trial sequential analysis was used to evaluate evidence conclusiveness. Data from 9 studies (604 patients) were analyzed. The median (range) of IMMPACT recommendations met in these trials was 9 (5, 15) of 21. Paravertebral block was not different from Control group in preventing CPSP at 3 months, but was protective at 6 months, with relative risk reduction (95% confidence interval) of 54% (0.24-0.88) (P = 0.02). Meta-regression suggested that the relative risk of CPSP was lower when single-injection (R = 1.00, P < 0.001) and multilevel (R = 0.71, P = 0.01) PVB were used. Trial sequential analysis revealed that 6-month analysis was underpowered by at least 312 patients. Evidence quality was moderate according to the GRADE system. Evidence suggests that multilevel single-injection PVB may be protective against CPSP at 6 months after BCS, but methodological limitations are present. Larger trials observing IMMPACT recommendations are needed to confirm this treatment effect and its magnitude.

Psychosocial Stress Delays Recovery of Postoperative Pain Following Incisional Surgery in the Rat

Psychosocial factors such as anxiety, depression and catastrophizing, commonly associated with established chronic pain, also may be associated with an increased risk of chronic postsurgical pain (CPSP) when present preoperatively. We used a repeat social defeat (RSD) paradigm to induce psychosocial stress in rodents prior to incisional surgery of the paw. Mixed effects growth curve models were utilized to examine resolution of mechanical hypersensitivity in rats for four weeks following surgery. Eight days following surgery, immunohistochemistry was conducted to examine glial activation as well as evoked neuronal activation in the spinal cord. Here we document that RSD resulted in reduced weight gain and increased depressive symptoms prior to surgery. Rats exposed to RSD displayed delayed resolution of mechanical hypersensitivity in the ipsilateral paw following surgery compared to non-defeated rats. Prior exposure to RSD significantly increased microglial activation and neuronal sensitization (pERK-IR) within the ipsilateral spinal cord. In conclusion, we found that chronic social stress alters the neurobiological response to surgical injury, resulting in slowed recovery. This model maybe useful for future interventional studies examining the mechanistic interactions between depression and risk of CPSP.

Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain.

The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1,152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNF mice compared with BDNF group after plantar incision. This study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain.