Capsaicin 8% Patch and Chronic Postsurgical Neuropathic Pain

(1) Background: Surgery is a frequent cause of persistent pain, defined chronic post-surgical pain (CPSP). The capsaicin 8% patch (Qutenza®) is approved for the treatment of postherpetic neuralgia (PHN) and for diabetic peripheral neuropathy (DPN) of the feet. We propose a review of the literature on use of the capsaicin 8% patch to treat neuropathic pain associated with surgery; (2) Methods: We identified the articles by searching electronic databases using a combination of such terms as “capsaicin 8% patch”, “Qutenza®”, and “chronic postsurgical pain”; (3) Results: We identified 14 selected studies reporting on a total of 632 CPSP cases treated with capsaicin 8% patch. Treatment with the capsaicin 8% patch significantly reduced the average pain intensity. Only 5 studies reported adverse events (AEs) after the patch application. The most common AEs were erythema, burning sensation and pain; (4) Conclusions: Our review indicate that capsaicin 8% patch treatment for CPSP is effective, safe and well tolerated, but randomized controlled trials on efficacy, safety and tolerability should be conducted.

Effect of perioperative cognitive behavioral therapy on chronic post-surgical pain among breast cancer patients with high pain catastrophising characteristics: Protocol for a double-blinded randomised controlled trial.

BackgroundSurgery is regarded as the primary treatment for breast cancer. Chronic post-surgical pain (CPSP) is a recognised complication after breast cancer surgery, and it is estimated to affect 20–30% of women. Pain catastrophizing has emerged as one of the most influential psychological variables associated with CPSP.MethodsThis trial will be a single-centre, prospective, double-blinded, noninferiority, randomised controlled trial (RCT). Patients scheduled for elective breast cancer surgery (wide local excision or mastectomy with or without axillary lymph node dissection) will be screened preoperatively for high pain catastrophising. Patients with high pain catastrophising, defined as a score of ≥ 24 on the Pain Catastrophising Scale will be deemed eligible for inclusion in the study. Participants will be randomly assigned to receive either a cognitive behavioural therapy or an educational mindfulness based program during their perioperative period. The primary outcome is the Brief Pain Inventory short form average pain severity score at three months postoperatively. Secondary outcomes include patient-reported quality of recovery at Day 1–2 after surgery, levels of pain catastrophising, reported depressed mood and anxiety. ]DiscussionTo the best of our knowledge, this protocol describes the first RCT which directly examines the effect of perioperative cognitive behavioural therapy on CPSP among breast cancer patients with high pain catastrophising characteristics. The outcomes of this trial may have significant implications for these patients because perioperative cognitive behavioural therapy has the potential to become an important perioperative intervention to complement patient management.Trial registrationThis trial is registered on ClinicalTrials.gov Identifier: NCT04924010 on 11th June 2021. All item from the World Health Organisation Trial Registration Data set have been included. https://clinicaltrials.gov/ct2/show/NCT04924010

Epigallocatechin-3-Gallate Modulates Postoperative Pain by Regulating Biochemical and Molecular Pathways

Treating postoperative (PO) pain is a clinical challenge. Inadequate PO pain management can lead to worse outcomes, for example chronic post-surgical pain. Therefore, acquiring new information on the PO pain mechanism would increase the therapeutic options available. In this paper, we evaluated the role of a natural substance, epigallocatechin-3-gallate (EGCG), on pain and neuroinflammation induced by a surgical procedure in an animal model of PO pain. We performed an incision of the hind paw and EGCG was administered for five days. Mechanical allodynia, thermal hyperalgesia, and motor dysfunction were assessed 24 h, and three and five days after surgery. At the same time points, animals were sacrificed, and sera and lumbar spinal cord tissues were harvested for molecular analysis. EGCG administration significantly alleviated hyperalgesia and allodynia, and reduced motor disfunction. From the molecular point of view, EGCG reduced the activation of the WNT pathway, reducing WNT3a, cysteine-rich domain frizzled (FZ)1 and FZ8 expressions, and both cytosolic and nuclear β-catenin expression, and the noncanonical β-catenin–independent signaling pathways, reducing the activation of the NMDA receptor subtype NR2B (pNR2B), pPKC and cAMP response element-binding protein (pCREB) expressions at all time points. Additionally, EGCG reduced spinal astrocytes and microglia activation, cytokines overexpression and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway, downregulating inducible nitric oxide synthase (iNOS) activation, cyclooxygenase 2 (COX-2) expression, and prostaglandin E2 (PGE2) levels. Thus, EGCG administration managing the WNT/β-catenin signaling pathways modulates PO pain related neurochemical and inflammatory alterations.

Effect of perioperative use of parecoxib on chronic post-surgical pain in elderly patients after hepatectomy: a prospective randomized controlled study

Background Chronic post-surgical pain (CPSP) has a negative impact on the recovery, quality of life, and physical functioning of elderly patients. This study aimed to test the superiority of parecoxib vs. placebo in preventing chronic post-hepatectomy pain in elderly patients under combined general-epidural anesthesia. Methods A total of 105 elderly patients undergoing hepatectomy under combined general-epidural anesthesia were randomized into the parecoxib or placebo group. The primary outcome was the proportion of patients with CPSP 3 months postoperatively. The secondary outcomes included the Short-Form McGill Pain Questionnaire score in CPSP-positive responders, acute pain intensity, postoperative analgesic demand, inflammatory markers change, and postoperative complications within 28 days. Results The parecoxib group provided a non-significant absolute 9.1% reduction in the rate of CPSP compared to the placebo group (P = 0.34). The average chronic pain visual analog scale in the parecoxib group was lower than that in the placebo group (P = 0.04). Significantly less moderate-to-severe acute pain at rest (P = 0.04) and with coughing (P < 0.001), less patient-controlled epidural analgesia (PCEA) consumption (P = 0.01), and less rescue analgesia (P < 0.001) were observed in the parecoxib group compared to the placebo group. Furthermore, no between-group difference was observed in inflammatory markers (P > 0.05) and postoperative complications (P = 0.65). Conclusions Parecoxib reduced the prevalence of CPSP in elderly patients after hepatectomy under combined general-epidural anesthesia from 44.4 to 35.3% with no statistical significance. Moreover, significantly alleviated CPSP intensity and improved acute pain management were observed. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/edit.aspx?pid=56961&htm=4) on August 3, 2020 (ChiCTR-2,000,035,198).

Prognostic factors for chronic post-surgical pain after lung or pleural surgery: a protocol for a systematic review and meta-analysis

IntroductionChronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence.Methods and analysisThe reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of at least 3 months reporting patient-related factors and surgery-related factors for any adult population. Randomised controlled trials will be included if they report on prognostic factors for CPSP after lung or pleural surgery. We will exclude case series, case reports, literature reviews, studies that do not report results for lung or pleural surgery separately and studies that modified the treatment or prognostic factor based on pain during the observation period. MEDLINE, Scopus, Web of Science, Embase, Cochrane, CINAHL, Google Scholar and relevant literature reviews will be searched. Independent pairs of two reviewers will assess studies in two stages based on the PICOTS criteria. We will use the Quality in Prognostic Studies tool for the quality assessment and the CHARMS-PF checklist for the data extraction of the included studies. The analyses will all be conducted separately for each identified prognostic factor. We will analyse adjusted and unadjusted estimated measures separately. When possible, evidence will be summarised with a meta-analysis and otherwise narratively. We will quantify heterogeneity by calculating the Q and I2 statistics. The heterogeneity will be further explored with meta-regression and subgroup analyses based on clinical knowledge. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guideline 28.Ethics and disseminationEthical approval will not be necessary, as all data are already in the public domain. Results will be published in a peer-reviewed scientific journal.PROSPERO registration numberCRD42021227888.

Differential Risk Factor Profiles in the Prediction of General and Pain-Specific Functional Limitations 12 Months after Major Pediatric Surgery

Pediatric chronic post-surgical pain is a surgical complication associated with various levels of functional limitation. Two commonly used measures of functional limitations in youth are the Functional Disability Inventory (FDI) and the PROMIS Pediatric Pain Interference Scale (PPIS), where the former is general, and the latter, pain specific. The aim of the present study was to prospectively compare pre-surgical youth and parent risk factors for youth functional limitations, assessed by the FDI and PPIS, 12 months after major pediatric surgery. Risk factors for the FDI and PPIS were compared in 79 dyads consisting of youth (58% female, M = 14.56 years; SD = 2.31) undergoing major surgery and one of their parents. The FDI and PPIS were highly correlated prior to surgery (r = 0.698, p < 0.001) and even more so 12 months after surgery (r = 0.807, p < 0.001). Parent pre-surgical anxiety sensitivity and youth pre-surgical functional disability significantly predicted 12-month FDI (F(6,56) = 4.443, p = 0.001, Adjusted R2 = 0.25), whereas parent pre-surgical anxiety sensitivity, trait anxiety, pain anxiety, as well as youth pain-related anxiety and worry significantly predicted 12-month PPIS (F(6,45) = 4.104, p = 0.002, Adjusted R2 = 0.27). Risk factors for 12-month general and pain-specific functional limitations differ by dyad member and type. Functional limitations in youth after surgery are predicted by youth and parent factors, however the risk factors differ between the FDI and the PPIS.

What Does CATS Have to Do With Cancer? The Cognitive Activation Theory of Stress (CATS) Forms the SURGE Model of Chronic Post-surgical Pain in Women With Breast Cancer

Chronic post-surgical pain (CPSP) represents a highly prevalent and significant clinical problem. Both major and minor surgeries entail risks of developing CPSP, and cancer-related surgery is no exception. As an example, more than 40% of women undergoing breast cancer surgery struggle with CPSP years after surgery. While we do not fully understand the pathophysiology of CPSP, we know it is multifaceted with biological, social, and psychological factors contributing. The aim of this review is to advocate for the role of response outcome expectancies in the development of CPSP following breast cancer surgery. We propose the Cognitive Activation Theory of Stress (CATS) as an applicable theoretical framework detailing the potential role of cortisol regulation, inflammation, and inflammatory-induced sickness behavior in CPSP. Drawing on learning theory and activation theory, CATS offers psychobiological explanations for the relationship between stress and health, where acquired expectancies are crucial in determining the stress response and health outcomes. Based on existing knowledge about risk factors for CPSP, and in line with the CATS position, we propose the SURGEry outcome expectancy (SURGE) model of CPSP. According to SURGE, expectancies impact stress physiology, inflammation, and fear-based learning influencing the development and persistence of CPSP. SURGE further proposes that generalized response outcome expectancies drive adaptive or maladaptive stress responses in the time around surgery, where coping dampens the stress response, while helplessness and hopelessness sustains it. A sustained stress response may contribute to central sensitization, alterations in functional brain networks and excessive fear-based learning. This sets the stage for a prolonged state of inflammatory-induced sickness behavior – potentially driving and maintaining CPSP. Finally, as psychological factors are modifiable, robust and potent predictors of CPSP, we suggest hypnosis as an effective intervention strategy targeting response outcome expectancies. We here argue that presurgical clinical hypnosis has the potential of preventing CPSP in women with breast cancer.