Risk Of Chronic Postsurgical Pain Research Articles

From pain level to pain experience: redefining acute pain assessment to enhance understanding of chronic postsurgical pain

BackgroundChronic postsurgical pain (CPSP) significantly impairs quality of life and poses a substantial healthcare burden, affecting up to a quarter of patients undergoing surgery. Although acute pain is recognised as a predictor for CPSP development, the role of patient experience remains underexplored. This study examines the predictive value of patient experience alongside traditional risk factors for CPSP after orthopaedic surgery. MethodsAn exploratory analysis was conducted on 294 patients from a multicentre randomised clinical trial comparing continuous perineural analgesia and single-injection nerve block in ambulatory orthopaedic surgeries. Patient experience was assessed using the Evaluation du Vecu de l’Anesthésie Générale (EVAN-G) validated questionnaire. Factors associated with CPSP at 90 days after surgery were identified through univariate and multivariate analyses, incorporating patient-reported outcomes and classical variables. ResultsOut of 219 patients with complete data, 63 (29%) developed CPSP at day 90. Multivariate analysis revealed a poor pain experience, as assessed by the pain dimension of EVAN-G on postoperative day 2, as an independent predictor of CPSP (odds ratio 6.45, 95% confidence interval 1.65–25.26, P<0.01). Poor pain experience was associated with an augmented risk of CPSP. ConclusionsThis study underscores the role of patient-reported outcomes, specifically the pain experience dimension captured by the EVAN-G scale, in prediction of CPSP 90 days after surgery. It suggests a shift from conventional assessments of pain intensity to a comprehensive understanding of pain experience, advocating for tailored pain management approaches that could reduce chronic pain, thereby improving patient quality of life and functional recovery.

Development and internal validation of a clinical risk tool to predict chronic postsurgical pain in adults: a prospective multicentre cohort study

Abstract Chronic postsurgical pain (CPSP) is a highly prevalent condition. To improve CPSP management, we aimed to develop and internally validate generalizable point-of-care risk tools for preoperative and postoperative prediction of CPSP 3 months after surgery. A multicentre, prospective, cohort study in adult patients undergoing elective surgery was conducted between May 2021 and May 2023. Prediction models were developed for the primary outcome according to the International Association for the Study of Pain criteria and a secondary threshold-based CPSP outcome. Models were developed with multivariable logistic regression and backward stepwise selection. Internal validation was conducted using bootstrap resampling, and optimism was corrected by shrinkage of predictor weights. Model performance was assessed by discrimination and calibration. Clinical utility was assessed by decision curve analysis. The final cohort included 960 patients, 16.3% experienced CPSP according to the primary outcome and 33.6% according to the secondary outcome. The primary CPSP model included age and presence of other preoperative pain. Predictors in the threshold-based models associated with an increased risk of CPSP included younger age, female sex, preoperative pain in the surgical area, other preoperative pain, orthopedic surgery, minimally invasive surgery, expected surgery duration, and acute postsurgical pain intensity. Optimism-corrected area-under-the-receiver-operating curves for preoperative and postoperative threshold-based models were 0.748 and 0.747, respectively. These models demonstrated good calibration and clinical utility. The primary CPSP model demonstrated fair predictive performance including 2 significant predictors. Derivation of a generalizable risk tool with point-of-care predictors was possible for the threshold-based CPSP models but requires independent validation.

Risk factors for persistent postoperative opioid use: an entity distinct from chronic postsurgical pain

Despite a decline in opioid prescriptions over the past decade, patients commonly receive opioid analgesics as a treatment for postoperative pain in the USA. One complication that patients may experience...

The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center

Study ObjectiveTo determine if baseline cytokines/chemokines and their changes over postoperative days 0–2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. DesignProspective, observational, longitudinal nested study. SettingUniversity-affiliated quaternary children’s hospital. PatientsSubjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. MeasurementsDemographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score > 3/10 beyond 3 months post-surgery) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. Main ResultsAnalyses included 3,164 repeated measures of 16 cytokines/chemokines from 112 subjects (median age 15.3, IQR 13.5–17.0, 54.5 % female, 59.8 % pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (β = 0.95, SE 0.31; p = 0.003), IL-1β (β = 0.84, SE 0.36; p = 0.02), IL-2 (β = 0.78, SE 0.34; p = 0.03), and IL-12 p70 (β = 0.88, SE 0.40; p = 0.03) and longitudinal postoperative elevations in GM-CSF (β = 1.38, SE 0.57; p = 0.03), IFNγ (β = 1.36, SE 0.6; p = 0.03), IL-1β (β = 1.25, SE 0.59; p = 0.03), IL-7 (β = 1.65, SE 0.7; p = 0.02), and IL-12 p70 (β = 1.17, SE 0.58; p = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β = -0.39, SE 0.17; p = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β = -0.57, SE 0.26; p = 0.03), IL-8 (β = -0.68, SE 0.24; p = 0.006), and IL-13 (β = -0.48, SE 0.22; p = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively. ConclusionWe identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.

Local Anesthetics, Local Anesthetic Systemic Toxicity (LAST), and Liposomal Bupivacaine.

Local anesthetics have played a vital role in the multimodal analgesia approach to patient care by decreasing the use of perioperative opioids, enhancing patient satisfaction, decreasing the incidence of postoperative nausea and vomiting, decreasing the length of hospital stay, and reducing the risk of chronic postsurgical pain. The opioid-reduced anesthetic management for perioperative analgesia has been largely successful with the use of local anesthetics during procedures such as peripheral nerve blocks and neuraxial analgesia. It is important that practitioners who use local anesthetics are aware of the risk factors, presentation, and management of local anesthetic systemic toxicity (LAST).

Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Dietary vitamin C intake and changes in frequency, severity, and location of pain in older adults.

Oral vitamin C supplementation has been associated with lower risk of chronic postsurgical pain. However, the effect of dietary vitamin C on pain in a non-surgical setting is unknown. We aimed to investigate the association between dietary vitamin C intake and changes over time in chronic pain and its characteristics in community-dwelling adults aged 60+ years. We pooled data from participants of the Seniors-ENRICA-1 (n=864) and Seniors-ENRICA-2 (n=862) cohorts who reported pain at baseline or at follow-up. Habitual diet was assessed with a face-to-face diet history and dietary vitamin C intake was estimated using standard food composition tables. Pain changes over time were the difference between scores at baseline and follow-up obtained from a pain scale that considered the frequency, severity, and number of pain locations. Multivariable-adjusted relative risk ratios (RRR) were obtained using multinomial logistic regression. After a median follow-up of 2.6 years, pain worsened for 696 (40.3%) participants, improved for 734 (42.5%), and did not change for 296 (17.2%). Compared to the lowest tertile of energy-adjusted vitamin C intake, those in the highest tertile had a higher likelihood of overall pain improvement (RRR 1.61 [95% confidence interval 1.07-2.41],p-trend 0.02). Higher vitamin C intake was also associated with lower pain frequency (1.57 [1.00-2.47],p-trend=0.05) and number of pain locations (1.75 [1.13-2.70],p-trend=0.01). Higher dietary vitamin C intake was associated with improvement of pain and with lower pain frequency and number of pain locations in older adults. Nutritional interventions to increase dietary vitamin C intake with the aim of improving pain management require clinical testing.

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.

Selective COX-2 Inhibitor Is Beneficial in Suppressing Chronic Postsurgical Pain in Esophageal Cancer Patients and May Prolong Patient Survival

Introduction: Chronic postsurgical pain (CPSP) is a common complication after surgical procedures. Radical resection of esophageal cancer is a complex procedure, one of the most extensive and traumatic surgical procedures in oncological surgery, and the incidence of postoperative chronic pain is high, seriously affecting patients’ postoperative recovery. Therefore, this study aimed to investigate the incidence of CPSP in patients with esophageal cancer and to analyze the risk factors associated with its occurrence in order to provide certain prevention and treatment ideas for clinical prevention and reduction of CPSP. Methods: Patients with radical esophageal cancer resection were selected as the study subjects, and the clinical data regarding to patients’ preoperative comorbidities, ASA grading, surgical method, use of selective COX-2 inhibitors, postoperative analgesic pump use, and patients’ postoperative tumor recurrence time were collected. The differences in clinical data between the CPSP group and no-CPSP group were compared to analyze the risk factors for the occurrence of CPSP. Results: A total of 262 patients were included; 57 (21.76%) developed CPSP, and there were statistical differences between the two groups in terms of selective COX-2 inhibitor and postoperative analgesic pump use rates and surgical modality (p < 0.05), and logistic regression analysis showed that age and length of surgery increased the risk of CPSP, perioperative selective COX-2 inhibitor use decreased the risk of CPSP occurrence (p < 0.05), the extent of tumor infiltration and regional lymph node metastasis were risk factors for shortening tumor-free survival (TFS), and age and use of selective COX-2 inhibitor were influential factors for prolonging TFS (p < 0.05). Conclusion: Patients with esophageal cancer have a high incidence of postoperative chronic pain, with youth and length of surgery being risk factors for CPSP, and perioperative pain management with selective COX-2 inhibitors can reduce the incidence of CPSP and is associated with prolonged TFS.

Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study

BackgroundBoth preoperative psychological symptoms and chronic postsurgical pain (CPSP) are prevalent conditions and major concerns among surgery patients, with inconclusive associations. MethodsBased on the China Surgery and Anaesthesia Cohort (CSAC), we recruited 8350 surgery patients (40–65 yr old) from two medical centres between July 2020 and March 2023. Patients with preoperative psychological symptoms (i.e. anxiety, depression, stress reaction, and poor sleep quality) were identified using corresponding well-established scales. We then examined the associations of individual preoperative psychological symptoms and major patterns of preoperative psychological symptoms (identified by k-means clustering analysis) with CPSP, and different pain trajectories within 3 months. Lastly, mediation analyses were conducted to elucidate the mediating role of surgery/anaesthesia-related factors and the presence of 1-month postoperative psychological symptoms on the studied associations. ResultsWe included 1302 (1302/8350, 15.6%) CPSP patients. When analysed separately, all studied preoperative psychological symptoms were associated with increased CPSP risk, with the most pronounced odds ratio noted for anxiety (1.52, 95% confidence interval [CI] 1.23–1.86). Compared with patients clustered in the minor symptom group, excess risk of CPSP and experiencing an increasing pain trajectory was increased among patients with preoperative psychological symptoms featured by sleep disturbances (odds ratio=1.46, 95% CI 1.25–1.70 for CPSP and 1.58, 95% CI 1.20–2.08 for increasing pain trajectory) and multiple psychological symptoms (1.84 [95% CI 1.48–2.28] and 4.34 [95% CI 3.20–5.88]). Mediation analyses revealed acute/subacute postsurgical pain and psychological symptoms existing 1 month after surgery as notable mediators of the observed associations. ConclusionsThe presence of preoperative psychological symptoms might individually or jointly increase the risk of chronic postsurgical pain or experiencing deterioration in pain trajectory. Interventions for managing acute/subacute postsurgical pain and psychological symptoms at 1 month after surgery might help reduce such risk. Clinical trial registrationChiCTR2000034039.

Does Immediate Long-Span Nerve Allograft Reconstruction Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection for Benign and Malignant Disease

Peripheral nerve injury can lead to chronic postsurgical pain (CPSP) and neuropathic pain following major surgery. Determine in patients undergoing ablative mandibular operations with transection of the trigeminal nerve: do those who undergo immediate repair, when compared to those whose nerves are not repaired, have a decreased or increased risk for CPSP or post-traumatic trigeminal neuropathic pain (PTTNp)? A multisite, retrospective cohort of patients who underwent resection of the mandible for benign or malignant disease with either no repair or immediate repair of the intentionally transected trigeminal nerve with a long-span nerve allograft were analyzed for the presence or absence of CPSP and PTTNp at 6months. The primary predictor was the immediate repair or no repair of the trigeminal nerve. The primary outcome was the presence or absence of CPSP and PTTNp at 6months postsurgery. There were 13 covariate variables, including age, sex, ethnicity, nerve injury, type of PTTNp, malignant or benign pathology and subtypes of each, use of radiation or chemotherapy, treatment of transected nerve end, longest follow-up time, pain scale, and onset of pain. Two-tailed Student's t test and Welch's t test were performed on mean scores and post hoc logistics and linear regression modeling were performed when indicated. The confidence level for statistical significance was P value <.05. There were 103 and 94 subjects in the immediate and no-repair groups, respectively. The incidence of CPSP in the no-repair group was 22.3% and PTTNp was 2.12%, while there was 3.8% CPSP and 0% PTTNp in the repair group, which was statistically significant (P= <.001). Logistic regression modeling showed a statistically significant inverse relationship between the immediate repair and the incidence of CPSP/PTTNp with an odds ratio of 0.43, 95% confidence interval 0.18 to 1.01, P=.05. Greater age, malignant pathology, and chemo/radiation treatments were covariates found more frequently in the no repair group. Immediate repair of an intentionally transected trigeminal nerve with a long-span nerve allograft during resection of the mandible for both benign and malignant disease appears to reduce CPSP and possibly eliminate the development of PTTNp.

Development and Validation of a Predictive Model for Chronic Postsurgical Pain After Arthroscopic Rotator Cuff Repair: A Prospective Cohort Study.

Chronic pain management continues to present a significant challenge following arthroscopic shoulder surgery. Our purpose was to detect chronic postsurgical pain (CPSP) in patients who had undergone arthroscopic rotator cuff repair (ARCR) and develop a nomogram capable of predicting the associated risk. We collected the demographic and clinical data of 240 patients undergoing ARCR in our hospital from January 2021 to May 2022. The pain level was monitored and evaluated three months after ARCR. LASSO regression was used to screen out pain-predictingfactors, which were subsequently used to construct a nomogram. Internal validation was carried out using Bootstrap resampling. The data of 78 patients who underwent ARCR in our hospital from August 2022 to December 2022 were also collected for external verification of the nomogram. The predictive model was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Age, duration of preoperative shoulder pain (DPSP), C-reactive protein (CRP), number of tear tendons, and American Shoulder and Elbow Surgical Score (ASES) were screened by LASSO regression as predictive factors for CPSP. These factors were then used to construct a chronic pain risk nomogram. The area under the curve (AUC) of the predictive and validation models were 0.756 (95% CI: 0.6386-0.8731) and 0.806 (95% CI: 0.6825-0.9291), respectively. Furthermore, the calibration curves and decision curve analysis (DCA) for both models indicated strong performance, affirming the reliability of this predictive model. The CPSP risk model that has been developed exhibits strong predictive capabilities and practical utility. It offers valuable support to clinical healthcare professionals in making informed treatment decisions, reducing the unnecessary use of analgesic drugs, and optimizing the allocation of medical resources.

Levels of preoperative cerebrospinal fluid pro-inflammatory mediators and chronic pain after total knee arthroplasty surgery.

Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre- and postsurgical chronic pain in TKA surgery. The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL-6, IL-8, TNF, fractalkine, and CSF-1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery. While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = -0.525; p = .002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized β coefficient [β]: .11; 95% confidence interval [CI]: 0.06-0.16; p < .001) and CSF fractalkine level (β: -.62; 95% CI: -1.10 to -0.15; p = .012) were independent predictors of CPSP severity 6 months after TKA surgery. We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP.

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.

Prognostic factors for chronic post-surgical pain after lung and pleural surgery: a systematic review with meta-analysis, meta-regression and trial sequential analysis.

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p=0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.

Change in perioperative neutrophil-lymphocyte ratio as a potential predictive biomarker for chronic postsurgical pain and quality of life: an ambispective observational cohort study.

Accurate and accessible predictors of chronic postsurgical pain (CPSP) to identify high-risk postsurgical patients are prerequisite for preventive and interventional strategies. We investigated the incidence and risk factors of CPSP after abdominal surgery, with a focus on plasma immunological markers. This was a retrospective analysis of patients who underwent abdominal surgery under general anesthesia at a tertiary center between January 2021 and January 2022. The preoperative demographics, laboratory test data, and surgical factors of the participants were collected from the electronic medical record system. Postoperative pain intensity and living conditions at 1 year after discharge from the hospital were assessed via a phone survey. Univariate and multivariate analyses were used to explore independent risk factors associated with CPSP. A total of 968 patients were included, and 13.53% (n = 131 of 968) of patients reported CPSP 1 year after surgery. Patients with older age, open surgery, higher American Association of Anesthesiologists classification, patient-controlled intravenous analgesia application, longer surgery duration, higher postoperative absolute neutrophil count, and neutrophil-lymphocyte ratio (NLR), lower postoperative absolute lymphocyte count, and higher white blood cell count, were more likely to suffer from CPSP. A changed ratio of NLR (postoperative to preoperative) ≥ 5 significantly correlated with CPSP, moderate to severe pain, maximum numeric rating score since discharge from the hospital, and affected quality of life. The changed ratio of NLR could be used for the early identification of patients at risk for CPSP and affect the quality of life to alert the clinician to undertake further assessment.

Microglial VDAC1 signaling modulates sleep deprivation-induced transition to chronic postsurgical pain.

This study verified that sleep deprivation before and after skin/muscle incision and retraction (SMIR) surgery increased the risk of chronic pain and investigated the underlying roles of microglial VDAC1 signaling. Adult mice received six hours of total sleep deprivation from one day prior to SMIR until the third days after surgery. Mechanical and heat-evoked pain was assessed before and within 21 days after surgery. Microglial activation and changes of VDAC1 expression and oligomerization were measured. Minocycline was injected to observe the effects of inhibiting microglial activation on pain maintenance. The VDAC1 inhibitor DIDS and oligomerization inhibitor VBIT-4 were used to determine the roles of VDAC1 signaling on microglial ATP release, inflammation (IL-1β and CCL2), and chronicity of pain. Sleep deprivation significantly increased the pain duration after SMIR surgery, activated microglia and enhanced VDAC1 signaling in the spinal cord. Minocycline inhibited microglial activation and alleviated sleep deprivation-induced pain maintenance. Lipopolysaccharide (LPS)-induced microglial activation was accompanied by increased VDAC1 expression and oligomerization, and more VDAC1 was observed on the cell membrane surface compared with control. DIDS and VBIT-4 rescued LPS-induced microglial ATP release and IL-1β and CCL2 expression. DIDS and VBIT-4 reversed sleep loss-induced microglial activation and pain chronicity in mice, similar to the effects of minocycline. No synergistic effects were found for minocycline plus VBIT-4 or DIDS. Perioperative sleep deprivation activated spinal microglia and increases the risk of chronic postsurgical pain in mice. VDAC1 signaling regulates microglial activation-related ATP release, inflammation, and chronicity of pain.

Opioid Dose, Pain, and Recovery following Abdominal Surgery: A Retrospective Cohort Study.

Background: The optimal dosage for opioids given to patients after surgery for pain management remains controversial. We examined the association of higher post-surgical opioid use with pain relief and recovery. Methods: We retrospectively enrolled adult patients who underwent elective abdominal surgery at our hospital between August 2021 and April 2022. Patients were divided into the “high-intensity” or “low-intensity” groups based on their post-surgical opioid use. Generalized estimating equation models were used to assess the associations between pain scores at rest and during movement on days 1, 2, 3, and 5 after surgery as primary outcomes. The self-reported recovery and incidence of adverse events were analyzed as secondary outcomes. Results: Among the 1170 patients in the final analysis, 293 were in the high-intensity group. Patients in the high-intensity group received nearly double the amount of oral morphine equivalents per day compared to those in the low-intensity group (84.52 vs. 43.80), with a mean difference of 40.72 (95% confidence interval (CI0 38.96−42.48, p < 0.001) oral morphine equivalents per day. At all timepoints, the high-intensity group reported significantly higher pain scores at rest (difference in means 0.45; 95% CI, 0.32 to 0.58; p < 0.001) and during movement (difference in means 0.56; 95% CI, 0.41 to 0.71; p < 0.001) as well as significantly lower recovery scores (mean difference (MD) −8.65; 95% CI, −10.55 to −6.67; p < 0.001). A post hoc analysis found that patients with moderate to severe pain during movement were more likely to receive postoperative high-intensity opioid use. Furthermore, patients in the non-high-intensity group got out of bed sooner (MD 4.31 h; p = 0.001), required urine catheters for shorter periods of time (MD 12.26 h; p < 0.001), and were hospitalized for shorter periods (MD 1.17 days; p < 0.001). The high-intensity group was at a higher risk of chronic postsurgical pain (odds ratio 1.54; 95% CI, 1.14 to 2.08, p = 0.005). Conclusions: High-intensity opioid use after elective abdominal surgery may not be sufficient for improving pain management or the quality of recovery compared to non-high-intensity use. Our results strengthen the argument for a multimodal approach that does not rely so heavily on opioids.

Prevention and Management of Chronic Postsurgical Pain and Persistent Opioid Use Following Solid Organ Transplantation: Experiences From the Toronto General Hospital Transitional Pain Service.

With >700 transplant surgeries performed each year, Toronto General Hospital (TGH) is currently one of the largest adult transplant centers in North America. There is a lack of literature regarding both the identification and management of chronic postsurgical pain (CPSP) after organ transplantation. Since 2014, the TGH Transitional Pain Service (TPS) has helped manage patients who developed CPSP after solid organ transplantation (SOT), including heart, lung, liver, and renal transplants. In this retrospective cohort study, we describe the association between opioid consumption, psychological characteristics of pain, and demographic characteristics of 140 SOT patients who participated in the multidisciplinary treatment at the TGH TPS, incorporating psychology and physiotherapy as key parts of our multimodal pain management regimen. Treatment by the multidisciplinary TPS team was associated with significant improvement in pain severity and a reduction in opioid consumption. Given the risk of CPSP after SOT, robust follow-up and management by a multidisciplinary team should be considered to prevent CPSP, help guide opioid weaning, and provide psychological support to these patients to improve their recovery trajectory and quality of life postoperatively.

Chronic postsurgical pain in children and young adults with cancer and choice of regional anesthesia for amputation and limb-sparing surgery.

Patients undergoing limb amputation (LA) or limb-sparing (LS) for lower extremity oncologic diagnoses are at similar risk for chronic postsurgical pain of neuropathic nature (CPSP/NP). Regional anesthesia (RA) techniques are pre-emptive measures to prevent the occurrence of the CPS/NP. However, recommendations for epidural (EP) versus peripheral nerve blocks (PNBs) lack in pediatric literature. This study investigates the incidence and duration of CPSP/NP and describes NP-directed regimens. Data on demographics, use of EP or PNB, duration of CPSP/NP, and NP-directed medication were retrospectively collected for LA and LS between 2009 and 2019. Mixed effects logistic regression was used to compare the odds of CPSP/NP between EP and PNB. Cox PH model with adjustment for clustering due to multiple surgeries on patients was used to quantify rate of pain relief between surgery groups (LA vs. LS) and RA groups (EP vs. PNB). The incidence of CPSP/NP was 36 (23.8%) after 165 surgeries (150 patients). The odds of CPSP/NP after PNB were 2.5 times those of CPSP/NP after EP (p=.11). The rate of pain relief at any instant after the EP was 1.2 times that after PNB (p=.3). The rate of pain relief for LS with EP was 1.9 times that of pain relief for LA with EP, a statistically significant difference (p=.03). Gabapentin was used (94.5%), with addition of amitriptyline (24.2%) and both amitriptyline and methadone (12.7%). The LS with the EP group had a significantly higher rate of relief of CPSP/NP than LA with EP. Odds of CPSP/NP after PNB were 2.5 times those of CPSP after EP.