Chronic Postsurgical Pain Research Articles

Chronic postsurgical pain: A European survey.

Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. To find predictive factors for CPSP in an international survey. Observational study. Multicentre European prospective observational trial. Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview. The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery. A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified. Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research. clinicaltrials.gov ID: NCT03834922.

Moderating effects of preoperative knee pain and pain catastrophizing on the relation between COMT rs4680 genotypes and chronic postsurgical pain in total knee arthroplasty patients

BackgroundThe Catechol-O-methyltransferase (COMT) gene, responsible for encoding an enzyme crucial in the metabolism of catecholamines, is known to play a significant role in pain perception. Polymorphisms within this gene, particularly the COMT rs4680 genotypes, have been linked to various acute pain phenotypes. This prospective cohort study examines interactions among the genetic polymorphism COMT rs4680 genotypes, preoperative knee pain, and pain catastrophizing in chronic postsurgical pain (CPSP) at 3, 6, and 12 months post-total knee arthroplasty (TKA). Study designA total of 280 patients undergoing primary unilateral TKA participated, sharing demographic details, preoperative knee pain levels, psychological variables (pain catastrophizing), and COMT rs4680 genotyping via venous blood samples. Telephone interviews at specified intervals enabled the application of binary logistic regressions and interaction models. ResultsSignificant influences of preoperative knee pain and pain catastrophizing on postsurgical outcomes were observed. Specifically, at the first time point (T1, 3 months post-TKA), a notable moderation effect was identified in preoperative knee pain (R2 change = 0.026, p = 0.026). The Johnson–Neyman regions of significance (RoS) indicated these moderation effects were significant above a threshold of 17.18 (p = 0.05), accounting for 26.4%. At the third time point (T3, 12 months post-TKA), a complex three-way interaction among genotypes (GG, GA, and AA carriers) was evident, resulting in an R2 change of 0.051 (p = 0.009). Here, the RoS for pain catastrophizing was above 32.74 for 30.5% of GG genotype carriers, above 22.38 for 50.8% of GA carriers, and below 11.94 for 63.2% of AA carriers. ConclusionThis study illuminates the significant role of the COMT Val158Met rs4680 polymorphism in susceptibility to prolonged pain following TKA. It also elucidates how these genetic genotypes interplay with preoperative knee pain and pain catastrophizing. Such intricate genetic-psychological-pain relationships necessitate additional investigation to confirm these findings and potentially guide post-TKA pain management strategies.

Machines, mathematics, and modules: the potential to provide real-time metrics for pain under anesthesia.

The brain-based assessments under anesthesia have provided the ability to evaluate pain/nociception during surgery and the potential to prevent long-term evolution of chronic pain. Prior studies have shown that the functional near-infrared spectroscopy (fNIRS)-measured changes in cortical regions such as the primary somatosensory and the polar frontal cortices show consistent response to evoked and ongoing pain in awake, sedated, and anesthetized patients. We take this basic approach and integrate it into a potential framework that could provide real-time measures of pain/nociception during the peri-surgical period. This application could have significant implications for providing analgesia during surgery, a practice that currently lacks quantitative evidence to guide patient tailored pain management. Through a simple readout of "pain" or "no pain," the proposed system could diminish or eliminate levels of intraoperative, early post-operative, and potentially, the transition to chronic post-surgical pain. The system, when validated, could also be applied to measures of analgesic efficacy in the clinic.

Xenon ameliorates chronic post-surgical pain by regulating mitophagy in microglia and rats mediated by PINK1/Parkin pathway.

Chronic post-surgical pain (CPSP) is one of the important causes of poor postoperative outcomes, the activation of microglia in the spinal cord is closely related to the generation, transmission and maintenance of CPSP. Xenon (Xe), an anesthetic gas, has been reported to be able to significantly reduce intraoperative analgesia and postoperative pain sensation at low doses. However, the mechanism of the regulatory effect of xenon on activated microglia after CPSP remains unclear. In this study, CPSP model rats were treated with 50% Xe inhalation for 1 h following skin/muscle incision and retraction (SMIR), once a day for 5 consecutive days, and then the painbehavioraltests (pain behavior indexes paw withdrawal mechanical threshold, PWMT and thermal withdrawal latency, TWL), microglial activation, oxidative stress-related indexes (malondialdehyde, MDA; superoxide dismutase, SOD; hydrogen peroxide, H2O2; and catalase, CAT), mitophagy and PINK1/Parkin pathway were examined. The present results showed that a single dose of Xe treatment in SMIR rat model could significantly improve PWMT and TWL in the short-term at a single treatment and long-term at multiple treatments. Xe treatment inhibited microglia activation and oxidative stress in the spinal dorsal horn of SMIR rats, as indicated by the decrease of Iba1 and MDA/H2O2 levels and the increase of SOD/CAT levels. Compared with the control group, Xe further increased the CPSP promoted Mito-Tracker (a mitochondrial marker) and LC3 (an autophagy marker) co-localization positive spots and PINK1/Parkin/ATG5/BECN1 (autophagy-related proteins) protein expression levels, and inhibited the Mito-SOX (a mitochondrial reactive oxygen species marker) positive signal, indicating that Xe promoted microglia mitophagy and inhibited oxidative stress in CPSP. Mechanistically, we verified that Xe promoted PINK1/Parkin signaling pathway activation. Xe plays a role in ameliorating chronic post-surgical pain by regulating the PINK1/Parkin pathway mediated microglial mitophagy and provide new ideas and targets for the prevention and treatment of CPSP.

Efficacy of Transcutaneous Electrical Acupoint Stimulation on Chronic Postsurgical Pain After Video-Assisted Thoracoscopic Lobectomy: Study Protocol for a Prospective Randomized Controlled Trial.

Patients undergoing video-assisted thoracoscopic lobectomy (VATL) often experience chronic postsurgical pain (CPSP). Postoperative pain can affect the recovery of postoperative lung function, prolong postoperative recovery time, and increase patient hospitalization expenses. Transcutaneous electrical acupoint stimulation (TEAS) is an alternative therapy based on acupuncture that has shown promise in postoperative recovery and pain management across various medical fields. However, research specifically focused on the improvement of CPSP after VATL is currently lacking. The purpose of this study is to evaluate whether TEAS can effectively reduce the severity and occurrence of chronic postsurgical pain in patients undergoing VATL. By investigating the potential benefits of TEAS in mitigating CPSP after VATL, this study aims to provide valuable clinical evidence to support the integration of TEAS into postoperative care protocols for patients undergoing VATL. This study is a prospective, single-center, double-blinded, randomized controlled trial to be conducted at the 920th Hospital of Joint Logistics Support Force. Eighty patients undergoing VATL will be randomly divided into an experimental group (TEAS group) and a control group (sham group). The experimental group will receive TEAS at bilateral PC6, LI4, LR3, LU5, TE5, and LI11. The control group will not receive TEAS at the same acupoints. Both groups will receive TEAS or no TEAS before anesthesia induction and 1-7days after surgery, with each session lasting 30min. The primary outcome will be the incidence of CPSP at 3months after surgery. Secondary outcomes will include the incidence of CPSP at 6months after surgery, the numerical rating scale (NRS) scores at 3 and 6months after surgery, as well as the NRS scores at 24, 48, and 72h after surgery, remifentanil consumption during general anesthesia, demand for rescue analgesics, number and duration of indwelling chest tubes, incidence of postoperative nausea and vomiting, and changes of norepinephrine (NE), cortisol (Cor), tumor necrosis factor (TNF- α), and interleukin 6 (IL-6) in serum. ChiCTR2300069458. Registered on March 16, 2023.

Preoperative frailty predicts postoperative pain after total knee arthroplasty in older patients: a prospective observational study.

Frailty is reportedly associated with postoperative adverse outcomes and may increase the risk of post-surgical pain. Our study aimed to explore whether frailty was an independent risk factor for pain after total knee arthroplasty (TKA) in older patients. Included in this prospective observational study were patients aged 65 or older who underwent primary TKA. Frailty of the patients was assessed before surgery using the comprehensive geriatric assessment-frailty index and pain was evaluated before and after surgery using the Numerical Rating Scale. Of the 164 patients including 125 females with a mean age of 71.4 ± 4.6years, 51 patients were identified as being frail. Patients with chronic post-surgical pain had a significantly higher frailty index than those without chronic post-surgical pain, which was the same in patients with acute post-surgical pain. After adjusting for other confounding factors, frailty was shown to be an independent risk factor for both acute (OR: 13.23, 95% CI 3.73-46.93, P < 0.001) and chronic post-surgical pain (OR: 4.24, 95% CI 1.29-14.00, P = 0.02). The area under the receiver operating characteristic curve for frailty predicting chronic post-surgical pain was 0.73 (P < 0.001, 95% CI 0.65-0.81). Our findings demonstrated that preoperative frailty in older patients was a predictor of acute and chronic post-surgical pain after TKA, suggesting that frailty assessment should become a necessary procedure before operations, especially in older patients.

Time-Dependent Prediction Models for Individual Prognosis of Chronic Postsurgical Pain following Knee Replacement Based on an Extensive Multivariable Data Set

(1) Background: Clinically useful prediction models for chronic postsurgical pain (CPSP) in knee replacement (TKA) are lacking. (2) Methods: In our prospective, multicenter study, a wide-ranging set of 91 variables was collected from 933 TKA patients at eight time points up to one year after surgery. Based on this extensive data pool, simple and complex prediction models were calculated for the preoperative time point and for 6 months after surgery, using least absolute shrinkage and selection operator (LASSO) 1se and LASSO min, respectively. (3) Results: Using preoperative data only, LASSO 1se selected age, the Revised Life Orientation Test on pessimism, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)—subscore pain and the Timed “Up and Go” Test for prediction, resulting in an area under the curve (AUC) of 0.617 and a Brier score of 0.201, expressing low predictive power only. Using data up to 6 months after surgery, LASSO 1se included preoperative Patient Health Questionnaire-4, Knee Injury and Osteoarthritis Outcome Score (KOOS)—subscore pain (pain) 3 months after surgery (month), WOMAC pain 3 and 6 months, KOOS subscore symptoms 6 months, KOOS subscore sport 6 months and KOOS subscore Quality of Life 6 months. This improved the predictive power to an intermediate one (AUC 0.755, Brier score 0.168). More complex models computed using LASSO min did little to further improve the strength of prediction. (4) Conclusions: Even using multiple variables and complex calculation methods, the possibility of individual prediction of CPSP after TKA remains limited.

A longitudinal study of the prevalence of post-surgical inguinodynia and the factors responsible for the development of chronic pain among the patients undergoing open hernioplasty at a tertiary care center

Background: Chronic groin pain (Inguinodynia) is a potential complication following inguinal hernia mesh repair and has a significant impact on the quality of life. The incidence varies among studies ranging between 0% and 62.9%. Aims and Objectives: The present study was conducted with the objectives of estimating the prevalence of post-surgical inguinodynia among the patients undergoing open hernioplasty. The secondary objective was to assess the factors associated with the development of post-surgical inguinodynia. Materials and Methods: A longitudinal study was carried out in a tertiary care center in Bangalore, Karnataka among the hernia patients attending the outpatient department of General Surgery department. A pro forma prepared with expert validation was used to collect details regarding pre-operative characteristics, type of anesthesia, intraoperative findings, and post-operative complications. The pain was assessed by the visual analog scale. Descriptive statistics and Chi-square test were used to identify the risk factors. Results: A total of 112 patients underwent hernioplasty. Out of this, 108 were males and 4 were females. The mean age of the patients was 48±10.8 years. Majority of them (84, 77.7%) presented with indirect inguinal hernia. The prevalence of inguinodynia at 3-month post-hernia surgery was 21.4% (n=24). Patients with significant pre-operative pain had higher chances of developing chronic pain (P=0.000). It was found that post-operative surgical site infection was associated with increased chances of development of chronic pain (P=0.000). Conclusion: Our study found that around one-fifth of the hernia patients had developed chronic post-surgical inguinal pain following open hernioplasty. There was no significant relationship between patients’ characteristics and development of chronic post-operative pain. The presence of pre-operative pain and post-operative infection in the patients was significantly associated with the development of chronic pain. Intraoperative nerve identification and chronic post-operative pain did not have a significant relationship in our study. Most of the patients who developed chronic pain had experienced only mild pain and none of them had severe inguinal pain. From the findings of our study, we would like to recommend that all measures must be taken to prevent and treat post-operative surgical site infection which leads to the development of chronic pain in patients.

A Prospective Cohort Study of Acute Pain and In-Hospital Opioid Consumption After Cardiac Surgery: Associations With Psychological and Medical Factors and Chronic Postsurgical Pain.

Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP. Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status. Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13]). Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories.

Innovative Program to Prevent Pediatric Chronic Postsurgical Pain: Patient Partner Feedback on Intervention Development

Background: The risk of developing chronic postsurgical pain (CPSP) in youth is related to psychological factors, including preoperative anxiety, depression, patient/caregiver pain catastrophizing, and poor self-efficacy in managing pain. While interventions exist to address these factors, they are generally brief and educational in nature. The current paper details patient partner feedback on the development of a psychologist-delivered perioperative psychological program (PPP) designed to identify and target psychological risk factors for CPSP and improve self-efficacy in managing pain. Methods: Qualitative interviews were conducted with two patients and their caregivers to discuss their surgical and pain management experience and to advise on components of the PPP. Results: Reflexive thematic analysis of interviews generated the following themes, which were incorporated into the content and implementation of the PPP: caregiver involvement, psychological and physical strategies for pain management, biopsychosocial pain education, intervention structure, and supporting materials. Conclusions: The development of a novel psychologist-led PPP is a promising approach to mitigate mental health risks associated with pediatric CPSP and potentially boost postoperative outcomes and family wellbeing. Integrating patient partner feedback ensures that the PPP is relevant, acceptable, and aligned with the needs and preferences of the patients it is designed to serve.

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.

Pain during the first year after scoliosis surgery in adolescents, an exploratory, prospective cohort study.

Approximately 50% of adolescents who have undergone scoliosis surgery still experience severe pain one year postoperatively. We explored the postoperative pain trajectory and the potential value of preoperative Thermal Quantitative Sensory Testing (T-QST) as predictor of chronic postsurgical pain after scoliosis surgery. Single-center prospective cohort study in adolescents undergoing scoliosis surgery. Prevalence of chronic postsurgical pain (CPSP) one year after scoliosis surgery and postsurgical pain course during this year. The need for rescue medication and the relationship between pre-operative T-QST, acute pain and CPSP. Thirty-nine patients (mean age 13.9 years; SD 1.9 years) completed the study. One year postoperatively, ten patients (26%) self-reported pain [numeric rating scale (NRS) score ≥ 4]) when moving and two (5%) when in rest. Four of these patients (10.3%) experienced neuropathic pain. The pre-operative cold pain threshold was lower (p = 0.002) in patients with CPSP at 12 months. Preoperative cold and heat pain thresholds were correlated with the number of moderate or severe pain reports (NRS ≥ 4) in the first week postoperatively (r -.426; p = 0.009 and r.392; p = 0.016, respectively). One year after scoliosis surgery, a significant part of patients (26%) still reported pain, some with neuropathic characteristics. Better diagnosis and treatment is needed; our study suggests that T-QST could be further explored to better understand and treat children with this negative outcome.

Assessment of the concordance between DN4 scores performed by the patient (self-assessment) or by the physician (hetero-assessment) to detect subacute neuropathic postoperative pain.

Centres dedicated to chronic postsurgical pain (CPSP) have been developed, but delays for accessing to it are generally long. Teleconsultation might be a means to facilitate access to care by allowing an initial triage. CPSPs are neuropathic pain in around half of the cases and their diagnosis is mainly based on the score obtained from validated questionnaires. Among them, those requiring a neurological examination (i.e. the Douleur Neuropathique en 4 questions [DN4]) have a better sensitivity and specificity, and should be preferred. However, effectiveness of a remote neurological examination remains to be established. The aim of this observational study is to check during a face-to-face consultation if, after a short training, a naïve patient is capable to self-assess the clinical signs of neuropathic sensations. Thirty patients with suspected neuropathic pain were seen in a face-to-face postoperative pain consultation. Before examination, the patient was instructed to fill the DN4 questionnaire, including the neurological examination. Once explanations were given and checked, the patient was left and completed it alone. Then, the pain physician performed the DN4 questionnaire. Inter-rater reliability between patient and pain physician was assessed for each item and for DN4 score with the Kappa coefficient. For each item of the DN4 questionnaire, Kappa coefficients were between 0.74 and 1, and could be considered as excellent. For DN4 ≥ 4, the Kappa coefficient was 0.86. Our results suggest that after a short training, a naïve patient is capable of recognizing and diagnosing symptoms of neuropathic pain. Our results suggest that self-assessment, carried out after brief training and using a simple tool, provides results comparable to those obtained by a specialist physician to diagnose symptoms of neuropathic pain. If the results of the current study are confirmed on a larger scale, self-assessment will help improve access to specialized chronic pain care by better orienting patients and opening up access to teleconsultations.

General practice management of chronic post-surgical pain in patients with hip fracture: a qualitative study.

Hip fractures are common among elderly people and often lead to chronic post-surgical pain (CPSP). Effective CPSP management when patients transition from hospital to community settings is essential, but has not been sufficiently researched. This study examined general practitioner (GP) perspectives on managing patients with CPSP after hip fractures in Shanghai, China. A descriptive qualitative study was performed wherein semi-structured interviews were conducted with GPs practicing in Shanghai who volunteered to participate. This study was initiated after a regional survey of general practice care for patients with CPSP following hip fracture. Six key themes emerged: (1) GPs' care priorities for patients with CPSP varied; (2) pharmacological management posed challenges in terms of selecting appropriate medications; (3) consultation time constraints hindered comprehensive management; (4) GPs desired better communication from hospitals at discharge; (5) limited access to services, such as pain specialists and allied health, obstructed optimal care delivery; and (6) patient nonadherence to CPSP treatment was an issue. Multiple patient-, provider-, and system-level factors affected GP care for patients with CPSP after hip fracture. Improved interdisciplinary communication and education on evidence-based CPSP guidelines are needed to address the knowledge gaps among GPs. Barriers to healthcare access must be minimized to facilitate guideline-based care.

Chronic post-surgical pain after knee arthroplasty: a role of peripheral nerve blocks.

Peripheral nerve blocks are an efficient method of pain control after total knee arthroplasty (TKA), but there is no report of their impact on chronic post-surgical pain (CPSP). This prospective observational study aimed to assess adductor canal block (ACB) and IPACK block (blocks vs. no blocks) on opioid consumption, postoperative pain score, chronic post-surgical pain 2 years after TKA. 166 patients (82 vs. 84) were analyzed. Opioid consumption was less in the group with blocks (9.74 ± 3.87 mg vs. 30.63 ± 11.52 mg) (p < 0.001). CPSP was present in 20.24% of patients in the group without blocks and 6.1% of patients with blocks (p = 0.011). Predictor variables of CPSP included pain before surgery (cut-off of 5.5), pain at rest (cut-off of 2.35), pain during active movement (cut-off: 2.5), and opioid consumption (cut-off: 8 mg). Peripheral nerve blocks provide adequate analgesia, significantly decrease opioid consumption, improve functional outcomes, and reduce CPSP 2 years after surgery.

Trajectories of pain and opioid use up to one year after surgery: analysis of a European registry

BackgroundLong-term opioid use after surgery is a crucial healthcare problem in North America. Data from European hospitals are scarce and differentiation of chronic pain has rarely been considered. MethodsIn a mixed surgical cohort of the PAIN OUT registry, opioid use and chronic pain were evaluated before surgery, and 6 and 12 months after surgery (M6/M12). Subgroups with or without opioid medication and pre-existing chronic pain were analysed. M12-chronic pain was categorised as chronic postsurgical pain (CPSP) meeting the ICD-11 definition, chronic pain related to surgery not meeting the ICD-11 definition, and chronic pain unrelated to surgery. Primary endpoint was the rate of M12 opioid users. Variables associated with M12 opioid use and patient-reported outcomes were evaluated. ResultsOf 2326 patients, 5.5% were preoperative opioid users; 4.4% and 3.5% took opioids at M6 and M12 (P<0.001). Chronic pain before operation and at M6/M12 was reported by 41.2%, 41.8%, and 34.7% of patients, respectively (P<0.001). The rate of M12 opioid users was highest in group unrelated (22.3%; related 8.3%, CPSP 1.5%; P<0.001). New opioid users were 1.1% (unrelated 7.1%, related 2.3%, CPSP 0.7%; P<0.001). M12 opioid users reported more pain, pain-related physical and affective interference, and needed more opioids than non-users. The predominant variable associated with M12 opioids was preoperative opioid use (estimated odds ratio [95% confidence interval]: 28.3 [14.1−56.7], P<0.001). ConclusionsOpioid use was low in patients with CPSP, and more problematic in patients with chronic pain unrelated to surgery. A detailed assessment of chronic pain unrelated or related to surgery or CPSP is necessary. Clinical trial registrationNCT02083835.

Cohort profile: the China surgery and anesthesia cohort (CSAC)

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40–65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.

Ventral tegmental area dopaminergic circuits participates in stress-induced chronic postsurgical pain in male mice

BackgroundChronic postsurgical pain (CPP) markedly impairs patients’ quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS.MethodsWe conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC.ResultsThe ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC.ConclusionCSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC.

Effects of Physical Exercise and Motor Activity on Depression and Anxiety in Post-Mastectomy Pain Syndrome.

Chronic post-surgical pain is a condition persisting for not less than 3 months after surgical intervention. It is evaluated that 25-60% of women who underwent breast cancer excision suffer from post-mastectomy pain syndrome, and anxiety, depression, sleep disturbance, and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. The aim of this study was to estimate the influence of physical activity on the intensity of pain, depression, and anxiety in women who underwent mastectomy for breast cancer removal. A prospective observational unicentric cohort study was performed. Patients were females who underwent unilateral or bilateral mastectomy. The Numerical Rating Scale (NRS) was used to measure pain intensity, Beck's Depression Inventory (BDI) for depression, and Generalized Anxiety Disorders-7 (GAD-7) for anxiety evaluation. Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH), and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All evaluations were assessed 3 and 6 months after the surgery. Adequate physical activity reduced the intensity of pain, depression, and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequately active women showed a reduction in biomarkers of inflammation, cortisol, ACTH, and an increase of BDNF. Our results suggest that physical activity can improve the quality of life, reduce the intensity of pain and inflammatory markers, and be useful in the reduction of associated anxiety and depression.

Effect of 5% lidocaine-medicated plaster in preventing chronic postsurgical pain after knee replacement: protocol for a randomized double-blind placebo-controlled trial.

With an aging population, knee arthroplasty is increasingly common; however, chronic postsurgical pain (CPSP) affects up to 30% of patients. This study aims to evaluate the efficacy of 5% lidocaine-medicated plaster (LP5) in preventing CPSP among patients undergoing knee arthroplasty. This is a dual-center, randomized, double-blind, placebo-controlled trial involving 128 adult patients scheduled for knee arthroplasty. Participants will be randomly assigned, stratified by center, to either the LP5 group or the placebo group (n = 64 per group). The LP5 or placebo group will apply the patch 1day before surgery and on postoperative days 1-3, with multimodal analgesia administered postoperatively. Multimodal analgesia will include intraoperative flurbiprofen axetil and postoperative patient-controlled sufentanil. The primary outcome is the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3 months postoperatively. Secondary outcomes will include WOMAC stiffness, function, and total scales; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale; 36-Item Short Form Health Survey (SF-36); postoperative pain scores; Visual Analog Scale (VAS) sleep scores; postoperative sufentanil consumption; need for rescue analgesia; length of Post-Anesthesia Care Unit (PACU) stay; length of hospital stay; and 90-day mortality. Safety outcomes will include assessments of hypotension, hypertension, bradycardia, tachycardia, arrhythmia, interventions for haemodynamic events, headache, dizziness, nausea, vomiting, local skin allergy, wound infection, and toxic reaction. Data will be analyzed following a modified intention-to-treat approach. This study aims to provide high-quality evidence for the efficacy and safety of LP5 in preventing CPSP in patients undergoing knee arthroplasty.