Development Of Chronic Postsurgical Pain Research Articles

Identifying predictive factors of the development of chronic post-surgical pain (CPPS)

Identifying predictive factors of the development of chronic post-surgical pain (CPPS)

Current concepts and targets for preventing the transition of acute to chronic postsurgical pain.

It is estimated that approximately a third of patients undergoing certain surgeries may report some degree of persistent pain postoperatively. Chronic postsurgical pain (CPSP) reduces quality of life, is challenging to treat, and has significant socio-economic impact. From an epidemiological perspective, factors that predispose patients to the development of CPSP may be considered in relation to the patient, the procedure or, the care environment. Prevention or management of transition from acute to chronic pain often need a multidisciplinary approach beginning early in the preoperative period and continuing beyond surgical admission. The current concepts regarding the role of central and peripheral nervous systems in chronification of pain may provide targets for future therapies but, the current evidence seems to suggest that a multimodal analgesic approach of preventive analgesia along with a continued follow-up and treatment after hospital discharge may hold the key to identify and manage the transitioning of acute to chronic pain. A comprehensive multidisciplinary approach with prior identification of risk factors, minimizing the surgical insult and a culture of utilizing multimodal analgesia and continued surveillance beyond the period of hospitalization is an important step towards reducing the development of chronic pain. A transitional pain service model may accomplish many of these goals.

Hyperbaric Oxygen Attenuates Chronic Postsurgical Pain by Regulating the CD73/Adenosine/A1R Axis of the Spinal Cord in Rats

Chronic postsurgical pain (CPSP) affects postoperative rehabilitation and quality of life in patients, but its mechanisms are still poorly understood. Hyperbaric oxygen (HBO) attenuates neuropathic pain in animal and human studies, but its efficacy for CPSP treatment and its underlying mechanism have not been elucidated. This study aimed to investigate the analgesic effect of HBO in a CPSP rat model and the role of spinal cord adenosine circulation in HBO-induced analgesia. A skin/muscle incision and retraction (SMIR) rat model was used to mimic CPSP, and HBO treatment (2.5 atmospheric absolute, 60 minutes) was administered once daily for 5 consecutive days beginning 3 days after surgery. The role of spinal cord adenosine circulation in HBO-induced analgesia was investigated using β-methylene ADP (a CD73 inhibitor), 8-cyclopentyl-1,3-dipropylxanthine (an A1R antagonist), or an intrathecal injection of adenosine. The mechanical paw withdrawal threshold was determined at different timepoints before and after surgery. The spinal cord adenosine and adenosine triphosphate (ATP) contents were analyzed using high-performance liquid chromatography, and the spinal cord expression of adenosine-1 receptor (A1R), extracellular 5′-nucleotidase (CD73), and adenosine kinase (ADK) was examined by Western blotting and immunofluorescence staining. The results showed that the mechanical paw withdrawal threshold of the ipsilateral hind paw and the adenosine content decreased, and the spinal cord expression of A1R, CD73, and ADK and ATP content increased within 14 days after surgery. HBO treatment alleviated mechanical allodynia, reduced ATP content, and increased adenosine content by activating CD73 but downregulated the spinal cord expression of A1R, CD73, and ADK. Intrathecal adenosine alleviated mechanical allodynia after SMIR and downregulated the spinal cord expression of A1R and CD73, and intrathecal β-methylene ADP or 8-cyclopentyl-1,3-dipropylxanthine attenuated the analgesic effect of HBO treatment on SMIR-induced CPSP. PerspectiveSpinal cord adenosine is involved in the occurrence and development of CPSP, and HBO treatment alleviates CPSP by regulating adenosine production/metabolism in the spinal cord. Thus, HBO may be employed for the treatment of CPSP with favorable efficacy.

Identification of Presurgical Risk Factors for the Development of Chronic Postsurgical Pain in Adults: A Comprehensive Umbrella Review.

Risk factors for the development of chronic postsurgical pain (CPSP) have been reported in primary studies and an increasing number of reviews. The objective of this umbrella review was to compile and understand the published presurgical risk factors associated with the development of CPSP for various surgery types. Six databases were searched from January 2000 to June 2023 to identify meta-analyses, scoping studies, and systematic reviews investigating presurgical CPSP predictors in adult patients. Articles were screened by title/abstract and subsequently by full text by two independent reviewers. The selected papers were appraised for their scientific quality and validity. Data were extracted and descriptively analyzed. Of the 2344 retrieved articles, 36 reviews were selected for in-depth scrutiny. The number of primary studies in these reviews ranged from 4 to 317. The surgery typesassessed were arthroplasty (n = 13), spine surgery (n = 8), breast surgery (n = 4), shoulder surgery (n = 2), thoracic surgery (n = 2), and carpal tunnel syndrome (n = 1). One review included a range of orthopedic surgeries; six reviews included a variety of surgeries. A total of 39 presurgical risk factors were identified, some of which shared the same defining tool. Risk factors were themed into six broad categories: psychological, pain-related, health-related, social/lifestyle-related, demographic, and genetic. The strength of evidence for risk factors was inconsistent across different reviews and, in some cases, conflicting. A consistently high level of evidence was found for preoperative pain, depression, anxiety, and pain catastrophizing. This umbrella review identified a large number of presurgical risk factors which have been suggested to be associated with the development of CPSP after various surgeries. The identification of presurgical risk factors is crucial for the development of screening tools to predict CPSP. Our findings will aid in designing screening tools to better identify patients at risk of developing CPSP and inform strategies for prevention and treatment.

Ultrasound-Guided Percutaneous Cryoneurolysis of the Antebrachial Cutaneous Nerves for the Management of Prolonged Acute Post-Surgical Forearm Pain: A Report of Two Cases.

Prolonged acute postsurgical pain (PAPSP) contributes to the development of chronic postsurgical pain, impaired rehabilitation, longer hospital stays, and decreased quality of life. For upper extremity analgesia, the duration of postoperative pain management with continuous brachial plexus peripheral nerve blocks is limited due to the risk of infection. Ultrasound-guided percutaneous cryoneurolysis provides extended analgesia and avoids the risks and inconveniences of indwelling catheters. We present 2 cases of PAPSP of the forearm effectively managed by the use of ultrasound-guided percutaneous cryoneurolysis to treat the medial, lateral, and posterior antebrachial cutaneous nerves.

The Impact of Acute Postoperative Pain in Developing Chronic Pain after Total Knee Arthroplasty.

While total knee arthroplasties (TKAs) are performed with the intent to reduce pain, chronic postsurgical pain (CPSP) is one of the most well-documented complications that can occur following surgery. This study aimed to assess whether perioperative factors, focusing on acute postsurgical pain and perioperative opioid consumption, were associated with the development of chronic postsurgical pain. Under general anesthesia, 108 patients underwent TKA and were treated postoperatively with a multimodal analgesia approach. Numeric Rating Scale (NRS) pain scores at rest and with movement were recorded on postoperative days 0-3, 7, 14, and 30. Patients were sent a survey to assess chronic pain at months 22-66, which was examined as a single-group post hoc analysis. Based on the responses, patients were either classified into the CPSP or non-CPSP patient group. Chronic postsurgical pain was defined as an NRS score ≥ 4 with movement and the presence of resting pain. The primary outcome was a change in NRS. There were no differences in NRS pain scores with movement in the first 30 days postoperatively between patients with CPSP and without CPSP. Each unit increase in resting pain on postoperative days 3 and 14 was associated with significantly greater odds of CPSP presence (OR = 1.52; OR = 1.61, respectively), with a trend towards greater odds of CPSP at days 7 and 30 (OR = 1.33; OR = 1.43, respectively). We found that very intense pain in the initial phase seems to be related to the development of CPSP after TKA.

Prognostic factors of chronic postsurgical pain following gastrointestinal surgery: A systematic review protocol.

Chronic postsurgical pain (CPSP) presents a considerable healthcare challenge, impacting patients, and healthcare providers, particularly in the context of gastrointestinal surgery. The notable incidence of CPSP in this specific surgical domain emphasizes the need to identify patients with a high risk of developing this condition. Despite various studies exploring this topic, a comprehensive systematic review focusing on prognostic factors of CPSP following gastrointestinal surgery is currently lacking. Therefore, the aim of this systematic review is, through systematically examination of existing literature, to assess both established and potentially novel prognostic factors, associated with CPSP following gastrointestinal surgery. Adhering to the Cochrane Handbook and the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist, we will use pre-established criteria based on Population, Intervention, Comparator, Outcome, Timing, and Setting (PICOT-S), to determine eligibility for inclusion. Essentially, this entails studies reporting on prognostic factors of CPSP following gastrointestinal surgery. Relevant studies will be identified through systematic searches in medical databases, examination of reference lists from included studies, and screening of Clinicaltrials.gov. No restrictions will be imposed regarding language, publication time or source, and both randomized trials and observational studies will be included. Data extraction will follow the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and for quality assessment, we will use the Quality in Prognosis Studies (QUIPS) tool. The aim for the systematic review is to identify and assess the prognostic value of potential factors for the development of CPSP following gastrointestinal surgery. By creating a comprehensive overview of important prognostic factors for the development of CPSP following gastrointestinal surgery, the findings of this systematic review have the potential to guide future research and to enhance patient information resources.

Risk factors and related miRNA phenotypes of chronic pain after thoracoscopic surgery in lung adenocarcinoma patients.

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.

Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial

BackgroundMastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25–60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP.MethodsKetamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale.DiscussionThis project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic.Trial registrationClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Evidence-based guideline on chronic postsurgical pain management in adult patients in resource-restricted setting, 2023: systematic review and guideline.

Chronic postsurgical pain (CPSP) after tissue trauma is frequent and may have a long-lasting impact on the functioning and quality of life. The development of CPSP increases the burden on both the patient and the community. This review aims to systematically review articles and, lastly, pull an evidence-based guideline for CPSP management in adult patients in resource-limited areas. The review was reported based on preferred reporting items for the systemic review and meta-analysis (PRISMA) protocol. A literature search was conducted from the Cochrane, PubMed/Medline, and Google Scholar databases, and other gray literature from 2010 to 2022. The conclusion was made based on the level of evidence. A total of 3521 articles were identified through the database by searching strategies. Finally, by filtering duplicates unrelated to the topics, 22 articles (9 meta-analyses and systematic reviews, 12 systematic reviews, and one cohort study) were selected on the management of CPSP in adult patients. Filtering was made based on the intervention, outcome data of the population, and methodological quality. Given the complexity and multidimensional nature of chronic postsurgical pain, effective assessment, and management require a comprehensive, multiaxial approach. Adequate preoperative preparation and counseling, potential risk identification and optimization, and use of a multimodal approach, and noninvasive surgical techniques are crucial in reducing the development of chronic postsurgical pain.

Postoperative Psychological Predictors for Chronic Postsurgical Pain After a Knee Arthroplasty: A Prospective Observational Study.

Chronic postsurgical pain (CPSP) is a significant adverse effect shown in around 20% of people who had undergone a knee arthroplasty (KA). Psychological risk factors have emerged as significant and potentially modifiable risk factors for its development. However, there is still little evidence when assessing these factors during the acute postoperative period. This study aimed to assess the predictive value of postoperative pain catastrophizing, pain-related fear of movement, anxiety, depression, and pain attitudes in developing CPSP after KA. A 6-month follow-up prospective observational study design was used. The study sample comprised 115 people who underwent a KA due to painful primary osteoarthritis. Measures of pain catastrophizing, pain-related fear of movement, anxiety, depression, and pain attitudes were obtained 1week after surgery. CPSP was set at an intensity of ≥30 using a 100-mm visual analog scale at 3 and 6months after surgery. Analysis revealed that baseline pain intensity, pain catastrophizing, pain-related fear of movement, anxiety, depression, and maladaptive pain attitudes were significant predictors of chronic pain at 3 and 6months after surgery in a univariate analysis. However, at 3months after surgery, only pain intensity and pain catastrophizing were predictors in the final multivariate model forecasting disturbing pain. Moreover, 6months after surgery, pain intensity and distrust in medical procedures remained independent predictors. Most of the psychological factors can be grouped into a single dimension defined as pain-related psychological distress. The results suggest that postoperative pain intensity, pain catastrophizing, and pain attitudes are independent predictors for CPSP after KA. Postoperative cognitive and emotional factors should be considered alongside pain intensity during postoperative rehabilitation after KA because they could influence the development of CPSP.

Impact of different doses of remifentanil on chronic postsurgical pain after video-assisted thoracic surgery: A propensity score analysis.

A remifentanil infusion dose of >0.2 μg/kg/min is associated with hyperalgesia, leading to acute postsurgical pain; however, its contribution to the development of chronic postsurgical pain after video-assisted thoracic surgery remains unclear. This study aimed to evaluate the impact of different remifentanil doses on chronic postsurgical pain after video-assisted thoracic surgery. This study included inpatients aged ≥ 55 years who underwent video-assisted thoracic surgery under general anesthesia between April 2016 and December 2018. An inverse probability of treatment weighted using stabilized inverse propensity scores was adopted to minimize bias. After adjustments based on patient data, the outcomes of interest were compared with intraoperative covariates using a generalized estimating equation. The primary study outcome was chronic postsurgical pain 1 year after surgery, defined as a pain score ≥1 on a numerical rating scale. Of the 262 eligible patients, 258 with a mean age of 71.2 years were included in this analysis. Chronic postsurgical pain occurred in 23.6% of patients. The generalized estimating equation revealed that a remifentanil infusion dose >0.2 μg/kg/min was associated with chronic postsurgical pain at 1 year after surgery (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.03-2.27), while remifentanil infusion doses >0.15 μg/kg/min (OR 1.12; 95% CI 0.79-1.59) and >0.175 μg/kg/min (OR 1.17; 95% CI 0.83-1.64) were not associated with our primary outcome. Remifentanil infusions >0.2 μg/kg/min were associated with chronic postsurgical pain 1 year after video-assisted thoracic surgery.

Pro-Con Debate: Role of Methadone in Enhanced Recovery After Surgery Protocols-Superior Analgesic or Harmful Drug?

Enhanced recovery after surgery (ERAS) protocols are standardized and designed to provide superior analgesia, reduce opioid consumption, improve patient recovery, and reduce hospital length of stay. Yet, moderate-to-severe postsurgical pain continues to afflict over 40% of patients and remains a major priority for anesthesia research. Methadone administration in the perioperative setting may reduce postoperative pain scores and have opioid-sparing effects, which may be beneficial for enhanced recovery. Methadone possesses a multimodal profile consisting of µ-opioid agonism, N-methyl-d-aspartate (NMDA) receptor antagonism, and reuptake inhibition of serotonin and norepinephrine. Furthermore, it may attenuate the development of chronic postsurgical pain. However, caution is advised with perioperative use of methadone in specific high-risk patient populations and surgical settings. Methadone's wide pharmacokinetic variability, opioid-related adverse effects, and potential negative impact on cost-effectiveness may also limit its use in the perioperative setting. In this PRO-CON commentary article, the authors debate whether methadone should be incorporated in ERAS protocols to provide superior analgesia with no increased risks.

A prospective study of chronic postsurgical pain in elderly patients: incidence, characteristics and risk factors

BackgroundDue to the continued growth of surgical procedures in older adults and the significant impact of chronic postsurgical pain (CPSP), it is crucial to improve our understanding of the occurrence of CPSP as well as the appropriate prevention and treatment. We therefore conducted this study to determine the incidence, characteristics and risk factors of CPSP in elderly patients at both 3 and 6 months after surgery.MethodsElderly patients (aged ≥ 60 years) undergoing elective surgery in our institution between April 2018 and March 2020 were prospectively enrolled in this study. Data on demographics, preoperative psychological well-being, intraoperative surgical and anesthesia management, and acute postoperative pain intensity were collected. At 3 and 6 months after surgery, patients received telephone interview and completed the questionnaires regarding chronic pain characteristics, analgesic consumption, and interference of the pain with activities of daily living (ADL).ResultsA total of 1065 elderly patients were followed up for 6 postoperative months and included in final analysis. At 3 and 6 months after operation, the incidence of CPSP was 35.6% [95% confidence interval (95% CI) 32.7 − 38.8%] and 21.5% (95% CI 19.0% − 23.9%), respectively. CPSP cause negative impacts on patient’s ADL and most particularly on mood. Neuropathic features were found in 45.1% of the patients with CPSP at 3 months. At 6 months, 31.0% of those with CPSP reported that the pain had neuropathic features. Preoperative anxiety [3 months: Odds ratio (OR) 2.244, 95% CI 1.693 to 2.973; 6 months: OR 2.397, 95% CI 1.745 to 3.294], preoperative depression (3 months: OR 1.709, 95% CI 1.292 to 2.261; 6 months: OR 1.565, 95% CI 1.136–2.156), orthopedic surgery (3 months: OR 1.927, 95% CI 1.112 to 3.341; 6 months: OR 2.484, 95% CI 1.220 to 5.061), higher pain severity on movement within postoperative 24 h (3 months: OR 1.317, 95% CI 1.191 to 1.457; 6 months: OR 1.317, 95% CI 1.177 to 1.475) were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery.ConclusionsCPSP is a common postoperative complication in elderly surgical patients. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population.

Role of the blood-spinal cord barrier: An adheren junction regulation mechanism that promotes chronic postsurgical pain

Chronic postsurgical pain (CPSP) is a serious postoperative complication with high incidence, and its pathogenesis involves neuroimmune interactions and the breakdown of the blood-spinal cord barrier (BSCB), the decreased level of adheren junction (AJ)-related proteins is an important cause of BSCB injury. Vascular endothelial-cadherin (VE-cadherin) and p120 catenin (p120) constitute the endothelial barrier adheren junction. The Src/p120/VE-cadherin pathway is involved in the regulation of the endothelial barrier function. However, the role of the BSCB-AJ regulatory mechanism in CPSP has not been reported. In this study, we established a skin/muscle incision and retraction (SMIR) model and evaluated the paw withdrawal threshold (PWT), the effects of an Src inhibitor and p120 knockdown on p-Src, p120 and VE-cadherin expression, as well as BSCB-AJ function in rat spinal cord were observed to explore the regulation of BSCB-AJ function by the p-Src/p120/VE-cadherin pathway in promoting SMIR-induced CPSP. The levels of p-Src, p120 and VE-cadherin in the spinal cord were detected by Western blot. Meanwhile, BSCB permeability test was used to detect the changes in BCSB function. Finally, the spatial and temporal localization of p120 in spinal cord was detected by immunofluorescence. Our findings indicated that p-Src/p120/VE-cadherin could induce BSCB-AJ dysfunction and promote the development of CPSP.

Preoperative Intravenous Dexamethasone and Postoperative Analgesia Following Breast Surgery: A Prospective, Randomized Double-Blind Trial at a Tertiary Healthcare Facility in Ghana.

Breast surgery may be associated with significant postoperative pain and if not adequately treated, may lead to the development of chronic post-surgical pain. This necessitates the use of effective management, involving the use a multimodal analgesia regimen for the management of post breast surgery pain. The analgesic effect of perioperative use of dexamethasone has been explored but findings have been inconsistent. The aim of this study was to determine the postoperative analgesic enhancing effect of a single preoperative dose of dexamethasone on patients undergoing breast surgery at a tertiary hospital in Ghana. This was a prospective, double-blind, placebo-controlled study involving 94 consecutively recruited patients. Patients were randomized into two groups: dexamethasone (n = 47) and placebo (n = 47). Patients in the dexamethasone group had 8mg (2 mL of 4 mg/mL) dexamethasone and those in the placebo group had 2 mL of saline administered intravenously just before induction of anaesthesia. All patients received a standard general anaesthesia with endotracheal intubation. The numerical rating score (NRS), time to first analgesic request and the total opioid consumed in the first 24 h were recorded. Patients receiving dexamethasone had lower NRS scores at all measured time points but this was significant only at 8 h post-surgery (P = 0.037). The time to first rescue analgesia was significantly prolonged in the dexamethasone group (339.26 ± 312.90 min vs. 182.10 ± 166.72 min; P = 0.020). However, the mean total opioid (pethidine) consumed in the first 24 h postoperatively was not significantly different between the dexamethasone and control groups (113.75 ± 51.35 mg vs. 100.00 ± 60.93 mg; P = 0.358). A single preoperative dose of 8mg dexamethasone given intravenously, reduces postoperative pain compared to placebo, significantly reduces the time to first analgesia but not the total opioid consumed in the first 24 h post breast surgery.

Study of the polymorphism of the ADRB2 molecular structure and its influence on the development of chronic postsurgical pain in children

Introduction. Pain is a signal to any aggression that leads to cellular damage and requires a defensive response. Uncontrolled acute perioperative visceral pain can lead to the development of pain chronicity. By studying the characteristics of chronic pain, some scientists have identified relationships with single-nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene. Purpose - to study the dependence of pain expression in the postoperative period in children on the polymorphism of the molecular structure of the ADRB2 receptor. Materials and methods. The study involved 42 children (20 boys and 22 girls) aged 7 to 18 years who were treated in the surgical department in 2020-2022 for acute appendicitis and peritonitis. Results. Based on the results of examining all the subjects under study, 13 children had the Arg16Gly polymorphism, 15 children had the Arg16Gly polymorphic variant, and 14 children were diagnosed with the homomorphic Gly16Gly polymorphism in the ADRB2. The data obtained confirmed the trend of the preliminary analysis and proved better body response to pain relief and reduced pain intensity in individuals with the Arg16Arg variant of the ADRB2. Analysis of the dependence between the polymorphism of the ADRB2 molecular structure and Visual Analogue Scale (VAS) scores in children in the postoperative period proved that the presence of Arg in the receptor phenotype had a strong negative correlation with the VAS score on discharge day (r=-0.822, p&lt;0.001), while the presence of Gly in the receptor phenotype had a strong positive correlation with the Visual Analogue Scale score on discharge day (r=0.814, p&lt;0.001). In regression analysis, the presence of Gly in the receptor phenotype was associated with a 1.917-fold increase in the VAS score at hospital discharge (OR: 1.917; 95% CI: 1.448-2.385; р&lt;0.001). Conclusions. The presence of the homomorphic Arg16Arg variant of the ADRB2 in children who underwent anterior abdominal wall surgery was accompanied by rapid response to analgesics. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Stress-induced changes in nociceptive responding post-surgery in preclinical rodent models.

Chronic post-surgical pain affects up to 85% of individuals depending on the type of surgery, the extent of inflammation, tissue and/or nerve damage. Pre-surgical stress is associated with greater pain intensity, prolonged recovery and is one of the main risk factors for the development of chronic post-surgical pain. Clinically valid animal models provide an important means of examining the mechanisms underlying the effects of stress on post-surgical pain and identifying potential novel therapeutic targets. This review discusses the current data from preclinical animal studies examining the effect of stress on post-surgical pain, the potential underlying mechanisms and gaps in the knowledge that require further investigation.

Pre- and post-operative psychological interventions to prevent pain and fatigue after breast cancer surgery (PREVENT): Protocol for a randomized controlled trial

Breast cancer is the most common cancer type among women worldwide with over a million new cases each year. More than 40% of these women will struggle with chronic pain and fatigue after surgery, regardless of surgical procedure. These consequences are detrimental and result in distress and disability, including work disability. Few attempts have been made to prevent chronic pain and fatigue after surgery by applying a psychological approach, despite psychological risk factors being crucial in the development of both chronic pain and fatigue. In this study, we aim to develop and test an easily implementable strategy of preventing chronic pain and fatigue after breast cancer surgery. The intervention strategy involves a pre-operative hypnosis session and a web-based post-operative Acceptance and Commitment Therapy (ACT). The hypnosis has previously been found effective in alleviating acute post-operative pain and fatigue in breast cancer patients, while ACT is well suited to cancer populations as it offers a model of healthy adaptation to difficult circumstances. Together they form an intervention strategy with both a preventive and a rehabilitative focus. This randomized controlled trial aims to estimate the effects of the pre- and post- operative interventions compared to attentional control and treatment as usual (TAU) and will also include a qualitative process evaluation. Participants will be randomized to receive either a pre-operative brief hypnosis session and a post-operative web-based psychological intervention (iACT) or a pre-operative one-session mindfulness through an audio file and post-operative TAU. Self-reported questionnaire data and biomarker data will be assessed pre-surgery, post-surgery and 3 and 12 months after surgery. In addition, we will assess registry data on sick leave and prescriptions until 2-year follow-up. In the qualitative process evaluation, data will be collected from participants from both study arms (through interviews and a diary) and two different analyses performed (socio-narrative and Grounded Theory) with the objective to describe the development of chronic post-surgical pain and fatigue and the potential influence of the interventions on these processes. The study is set-up to demonstrate a minimum difference in pain of 1 point on NRS (0-10) and 3 points on FACIT-F (0-52) between the groups at 3-months follow-up by including 200 breast cancer patients in total. This trial will be the first study to estimate the effect of a combined pre-operative hypnosis with a post-operative iACT to prevent pain and fatigue after breast cancer surgery. The results from our study might i) help the large group of women affected by chronic pain and fatigue after breast cancer surgery, ii) shed light on the mechanisms involved in chronic pain and fatigue development, and iii) serve as a model for other surgical procedures. Clinicaltrials.gov, registration number NCT04518085. Registered on January 29th, 2020. https://clinicaltrials.gov/ct2/show/NCT04518085.

Targeting Affective Mood Disorders With Ketamine to Prevent Chronic Postsurgical Pain.

The phencyclidine-derivative ketamine [2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one] was added to the World Health Organization's Model List of Essential Medicines in 1985 and is also on the Model List of Essential Medicines for Children due to its efficacy and safety as an intravenous anesthetic. In sub-anesthetic doses, ketamine is an effective analgesic for the treatment of acute pain (such as may occur in the perioperative setting). Additionally, ketamine may have efficacy in relieving some forms of chronic pain. In 2019, Janssen Pharmaceuticals received regulatory-approval in both the United States and Europe for use of the S-enantiomer of ketamine in adults living with treatment-resistant major depressive disorder. Pre-existing anxiety/depression and the severity of postoperative pain are risk factors for development of chronic postsurgical pain. An important question is whether short-term administration of ketamine can prevent the conversion of acute postsurgical pain to chronic postsurgical pain. Here, we have reviewed ketamine's effects on the biopsychological processes underlying pain perception and affective mood disorders, focusing on non-NMDA receptor-mediated effects, with an emphasis on results from human trials where available.