Role of caveolin-1 in chronic postsurgical pain in rats.
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SUBMITTER: Huang SS
PROVIDER: S-EPMC8461512 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors.ObjectiveTo find predictive factors for CPSP in an international survey.DesignObservational study.SettingMulticentre European prospective observational trial.PatientsPatients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA).MethodStandardised 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.Main outcome measureThe primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery.ResultsA 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.ConclusionUnfortunately, 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.Trial registrationclinicaltrials.gov ID: NCT03834922.
| S-EPMC10990022 | biostudies-literature
Project description:Chronic postsurgical pain (CPSP), with a high prevalence and rising epidemic of opioids crisis, is typically derived from acute postoperative pain. Revealing the peripheral mechanisms behind the transition from acute to chronic pain after surgery is necessary. We established on two recognized animal models, the Lateral Paw Incision (LPI) model and the Skin/Muscle Incision and Retraction (SMIR) model, in simulation of acute and chronic postsurgical pain. The tissue of incisional skin, muscle and DRG at several time points are harvested and send for next-generation RNA sequencing (RNA-seq). Then the quality of sequencing results is validated. Our data could explain the time-course transcriptomic variation in the tissue of skin, muscle and DRG, and further to identify the potential origin and mechanism of CPSP.
2024-10-08 | GSE267799 | GEO
Project description:Chronic postsurgical pain (CPSP) results from a cascade of events in the peripheral and central nervous systems following surgery. Several clinical predictors, including the prior pain state, premorbid psychological state (e.g., anxiety, catastrophizing), intraoperative surgical load (establishment of peripheral and central sensitization), and acute postoperative pain management, may contribute to the patient's risk of developing CPSP. However, research on the neurobiological and biobehavioral mechanisms contributing to pediatric CPSP and effective preemptive/treatment strategies are still lacking. Here we evaluate the perisurgical process by identifying key problems and propose potential solutions for the pre-, intra-, and postoperative pain states to both prevent and manage the transition of acute to chronic pain. We propose an eight-step process involving preemptive and preventative analgesia, behavioral interventions, and the use of biomarkers (brain-based, inflammatory, or genetic) to facilitate timely evaluation and treatment of premorbid psychological factors, ongoing surgical pain, and postoperative pain to provide an overall improved outcome. By achieving this, we can begin to establish personalized precision medicine for children and adolescents presenting to surgery and subsequent treatment selection.
| S-EPMC9067470 | biostudies-literature
Project description:Study objectiveTo determine if baseline cytokines 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 after (up to two weeks) 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) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.Main resultsAnalyses included 3,164 measures of 16 cytokines 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=.003), IL-1β (β=0.84, SE 0.36; p=.02), IL-2 (β=0.78, SE 0.34; p=.03), and IL-12 p70 (β=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (β=1.38, SE 0.57; p=.03), IFNγ (β=1.36, SE 0.6; p=.03), IL-1β (β=1.25, SE 0.59; p=.03), IL-7 (β=1.65, SE 0.7, p=.02), and IL-12 p70 (β=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β= -0.39, SE 0.17; p=.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=.03), IL-8 (β= -0.68, SE 0.24; p=.006), and IL-13 (β= -0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10.ConclusionWe identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.
| S-EPMC10996732 | biostudies-literature
Project description:Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that has a substantial effect on quality of life. CPSP shows considerable clinical overlap with different chronic peripheral pain syndromes, suggesting a shared aetiology. This study aims to assess the genetic overlap between different chronic pain syndromes and CPSP, providing relevant biological context for potential chronic pain markers of CPSP. To analyse the genetic overlap between CPSP and chronic peripheral pain syndromes, recent GWAS studies were combined for polygenic risk scores (PRS) analysis, using a cohort of CPSP patients as starting point. Biological contextualisation of genetic marker, overlap between CPSP and chronic pain syndromes, was assessed through Gene Ontology (GO), using Pathway Scoring Algorithm (PASCAL) and REVIGO. PRS analyses suggest a significant genetic overlap between CPSP and 3 chronic pain disorders: chronic widespread pain (CWP, p value threshold?=?0.003, R2 0.06, p?=?0.003), rheumatoid arthritis (RA, p value threshold?=?0.0177, R2?=?0.04, p?=?0.017) and possibly sciatica (p value threshold?=?0.00025, R2?=?0.03, p?=?0.045). Whereas no significant genetic overlap was found with cluster headache and migraine, the outcome for osteoarthritis (OA) was inconsistent between the cohorts. This is likely related to cohort composition, as repeated random reallocation of patients' nullified CPSP/OA outcome variation between the discovery and replication cohorts. GO analyses suggested an aetiological involvement of genetic markers that control neurological signalling (specifically sodium channels) and inflammatory response. The current study reaffirms the impact of sample size, cohort composition and open data accessibility on the unbiased identification of genetic overlap across disorders. In conclusion, this study is the first to report genetic overlap between regulatory processes implicated in CPSP and chronic peripheral pain syndromes. Interaction between neurological signalling and inflammatory response may explain the genetic overlap between CPSP, CWP and RA. Enhanced understanding of mechanisms underlying chronification of pain will aid the development of new therapeutic strategies for CPSP with sodium channel biochemistry as a potential candidate.
| S-EPMC7283206 | biostudies-literature
Project description:Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanism is not well understood. Accumulating evidence has suggested that central sensitization is the main mechanism of pain. To study the role of p120 in CPSP, a skin/muscle incision and retraction (SMIR) model was established, and immunofluorescence staining and western blotting were performed to analyze the expression of p120 in the spinal cord and dorsal root ganglion (DRG). The results demonstrated that SMIR increased the expression of p120 in the DRG and the spinal cord compared with the naive group. Furthermore, it was demonstrated that p120 was mainly distributed in the glial fibrillary acidic protein‑positive astrocytes in the spinal cord, and in the neurofilament 200‑positive medium and large neurons in the DRG. Our previous studies have shown that adenosine triphosphate‑sensitive potassium channel (KATP) agonists can reduce postoperative pain in rats. Therefore, the changes in p120 were observed in the DRG and spinal cord of rats following the intraperitoneal injection of nicorandil, a KATP agonist. It was demonstrated that nicorandil administration could relieve mechanical pain experienced following SMIR in rats, and decrease the expression of p120 in the DRG and spinal cord. The results revealed that p120 may contribute to the prophylactic analgesic effect of nicorandil, thus providing a novel insight into the mechanism of CPSP prevention.
| S-EPMC7646919 | biostudies-literature
Project description:ObjectiveApproximately 20% of patients experience chronic pain after total knee replacement (TKR), yet there is no consensus about how best to assess such pain. This systematic review aimed to identify measures used to characterize chronic pain after TKR.Methods. MEDLINE, Embase, PsycINFO, Cochrane Library, and CINAHL databases were searched for research articles published in all languages from January 2002 to November 2011. Articles were eligible for inclusion if they assessed knee pain at a minimum of 3 months after TKR, yielding a total of 1,164 articles. The data extracted included the study design,country, timings of assessments, and outcome measures containing pain items. The outcome measures were compared with domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials(IMMPACT) for inclusion in the assessment of chronic pain–related outcomes within clinical trials. Temporal trends were also explored.ResultsThe review found use of a wide variety of composite and single-item measures, with the American Knee Society Score the most common. Many measures used in published studies did not capture the multidimensional nature of pain recommended by the IMMPACT; of those commonly used, the Western Ontario and McMaster Universities Osteoarthritis Index and Oxford Knee Score were the most comprehensive. Geographic trends were evident, with nation-specific preferences for particular measures. A recent reduction in the use of some clinically administered tools was accompanied by an increased use of patient-reported outcome measures.ConclusionThere was wide variation in the methods of pain assessment alongside nation-specific preferences and changing temporal trends in pain assessment after TKR. Standardization and improvements in assessment are needed to enhance the quality of research and facilitate the establishment of a core outcome set.
| S-EPMC3883092 | biostudies-literature
Project description:AbstractChronic postsurgical pain (CPSP) is defined by pain intensity and pain-related functional interference. This study included measures of function in a composite score of patient-reported outcomes (PROs) to investigate the incidence of CPSP. Registry data were analyzed for PROs 1 day and 12 months postoperatively. Based on pain intensity and pain-related interference with function, patients were allocated to the groups " CPSPF " (at least moderate pain with interference), " mixed " (milder symptoms), and " no CPSPF ". The incidence of CPSPF was compared with CPSP rates referring to published data. Variables associated with the PRO-12 score (composite PROs at 12 months; numeric rating scale 0-10) were analyzed by linear regression analysis. Of 2319 patients, 8.6%, 32.5%, and 58.9% were allocated to the groups CPSPF , mixed , and no CPSPF , respectively. Exclusion of patients whose pain scores did not increase compared with the preoperative status, resulted in a 3.3% incidence. Of the patients without pre-existing pain, 4.1% had CPSPF. Previously published pain cutoffs of numeric rating scale >0, ≥3, or ≥4, used to define CPSP, produced rates of 37.5%, 9.7%, and 5.7%. Pre-existing chronic pain, preoperative opioid medication, and type of surgery were associated with the PRO-12 score (all P < 0.05). Opioid doses and PROs 24 hours postoperatively improved the fit of the regression model. A more comprehensive assessment of pain and interference resulted in lower CPSP rates than previously reported. Although inclusion of CPSP in the ICD-11 is a welcome step, evaluation of pain characteristics would be helpful in differentiation between CPSPF and continuation of pre-existing chronic pain.
| S-EPMC9667383 | biostudies-literature
Project description:Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated heritability for chronic pain is 45% and that genetic factors partially explain individual susceptibility to CPSP. The aim of this study was to systematically review, assess quality, and summarize the studies in humans that have investigated genetic factors associated with CPSP. We also conducted a meta-analysis to derive a single effect size for evaluable genetic associations with CPSP. Our comprehensive literature search included review of 21 full-text articles evaluating variants of 69 genes for association with CPSP. We found significant gene variant associations reported for variants/haplotypes of 26 genes involved in neurotransmission, pain signaling, immune responses and neuroactive ligand-receptor interaction, with CPSP. Six variants of 5 genes (COMT: rs4680 and rs6269, OPRM1: rs1799971, GCH1: rs3783641, KCNS1: rs734784 and TNFA: rs1800629), were evaluated by more than one study and were included in the meta-analysis. At rs734784 (A>G) of KCNS1, presence of G allele marginally increased risk of CPSP (Additive genetic model; Odds ratio: 1.511; 95% CI 1-2.284; P value: .050), while the other variants did not withstand meta-analyses criteria. Our findings demonstrate the role of genetic factors with different functions in CPSP, and also emphasize that single genetic factors have small effect sizes in explaining complex conditions like CPSP. Heterogeneity in surgical cohorts, population structure, and outcome definitions, as well as small number of available studies evaluating same variants, limit the meta-analysis. There is a need for large-scale, homogenous, replication studies to validate candidate genes, and understand the underlying biological networks underpinning CPSP. PERSPECTIVE: Our systematic review comprehensively describes 21 studies evaluating genetic association with CPSP, and limitations thereof. A meta-analysis of 6 variants (5 genes) found marginally increased risk for CPSP associated with rs734784 A>G of the potassium voltage-gated channel gene (KCNS1). Understanding genetic predisposition for CPSP will enable prediction and personalized management.
| S-EPMC6874752 | biostudies-literature
Project description:BackgroundPain after breast cancer surgery remains largely unexplained and inconsistently quantified. This study aims to describe the perioperative pain patterns in patients with breast cancer, up to two years after surgery.MethodsThis is a pre-planned sub-study of the Ketorolac in Breast Cancer (KBC) trial. The KBC trial was a multicentre, prospective, double-blind, placebo-controlled, randomised trial of a single dose of 30 mg of ketorolac just before breast cancer surgery, aiming to test its effect on recurrences. This sub-study focuses only on pain outcomes. From 2013 to 2015, 203 patients were randomised to ketorolac (n = 96) or placebo (n = 107). Structured questionnaires were delivered by telephone after one and two years, exploring the presence, location, permanence, and frequency of pain. Patients' perceptions of pain were captured by an open-ended question, the responses to which were coded and classified using hierarchical clustering.ResultsThere was no difference in pain between the ketorolac and the placebo group. The reported incidence of permanent pain was 67% and 45% at one and two years, respectively. The largest category was musculoskeletal pain. Permanent pain was mainly described in patients with musculoskeletal pain. The description of pain changed in most patients during the second postoperative year, i.e., moved from one category to another (no pain, permanent, or non-permanent pain, but also, the localisation). This phenomenon includes patients without pain at one year.ConclusionsPain is a complex phenomenon, but also a fragile and unstable endpoint. Pain after breast cancer surgery does not necessarily mean breast pain but also musculoskeletal and other pains. The permanence of pain and the pain phenotype can change over time.
| S-EPMC7759784 | biostudies-literature