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The association between genome-wide polymorphisms and chronic postoperative pain: a prospective observational study.

ABSTRACT: Chronic postoperative pain is common and can have a negative impact on quality of life. Recent studies show that genetic risk factors are likely to play a role, although only gene-targeted analysis has been used to date. This is the first genome-wide association study to identify single-nucleotide polymorphisms associated with the development of chronic postoperative pain based on two independent cohorts. In a discovery cohort, 330 women scheduled for hysterectomy were genotyped. A case-control association analysis compared patients without chronic postoperative pain and the 34 who had severe chronic postoperative pain 3 months after surgery. No single-nucleotide polymorphisms reached genome-wide significance, but several showed suggestive associations with chronic postoperative pain (p < 1 × 10-5 ). Single-nucleotide polymorphisms with significance p < 1 × 10-5 were followed up in a replication cohort consisting of 203 men and women scheduled for orthopaedic or abdominal surgery. Ten of these patients developed severe chronic postoperative pain. A single-nucleotide polymorphism in NAV3 was significantly replicated with chronic postoperative pain in the replication cohort (p = 0.009). Meta-analysis revealed that two loci (IQGAP1 and CRTC3) were significantly associated with chronic postoperative pain at 3 months (IQGAP1 p = 3.93 × 10-6 ? = 2.3863, CRTC3 p = 2.26 × 10-6 , ? = 2.4209). The present genome-wide association study provides initial evidence for genetic risk factors of chronic postoperative pain and supports follow-up studies.

SUBMITTER: van Reij RRI

PROVIDER: S-EPMC6973279 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The association between genome-wide polymorphisms and chronic postoperative pain: a prospective observational study.

van Reij R R I RRI Hoofwijk D M N DMN Rutten B P F BPF Weinhold L L Leber M M Joosten E A J EAJ Ramirez A A van den Hoogen N J NJ

Anaesthesia 20200101

Chronic postoperative pain is common and can have a negative impact on quality of life. Recent studies show that genetic risk factors are likely to play a role, although only gene-targeted analysis has been used to date. This is the first genome-wide association study to identify single-nucleotide polymorphisms associated with the development of chronic postoperative pain based on two independent cohorts. In a discovery cohort, 330 women scheduled for hysterectomy were genotyped. A case-control ...[more]

PMID: 31903573

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Project description:Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Project description:Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.

Project description:BackgroundPostoperative pain management is key for patient satisfaction. Pressure pain threshold (PPT) has been studied in some surgical cohorts but has not been studied in relationship to acute postoperative pain in short-stay patients undergoing anorectal surgery. We hypothesized that preoperative finger PPT measurements can identify respective patients with higher postoperative pain. Aiming to understand the relationship with subjective postoperative pain perception, we tested the hypotheses that preoperative PPT is associated with postoperative Visual Analog Scale (VAS) pain scores and correlates with postoperative analgesic consumption in short-stay patients undergoing anorectal surgery.MethodsWe prospectively assessed preoperative PPT in a cohort undergoing anorectal surgery, known as a moderately to severely painful procedure. Linear mixed-effects models were used to assess the relationship with postoperative VAS pain scores at 1 and 3 days as well as 4 weeks postoperatively. Logistic regression was used to study the relationship with additional postoperative analgesic consumption.ResultsWe studied 128 patients and found that preoperative PPT is significantly associated with postoperative pain (P value for interaction = .025). Logistic regression modeling additionally revealed an association between the preoperative PPT and the need for additional postoperative analgesics, with odds of requiring additional analgesia decreasing by about 10% for each 1-point increase in PPT (odds ratio [OR] = 0.90; 95% confidence interval [CI], 00.81-0.98; P = .012).ConclusionsPreoperative finger PPT is associated with postoperative pain and might help identify patients who are at risk of developing more severe postoperative pain on anorectal surgery. Especially in ambulatory and short-stay settings, this approach can help to address patients' high variability in pain sensitivity to facilitate appropriate postoperative analgesia, timely discharge, and prevent readmission.

Project description:PurposeHysterectomy is associated with a high incidence of chronic post-hysterectomy pain (CPHP). Pain catastrophizing, a negative cognitive-affective response to pain, is associated with various pain disorders but its role in CPHP is unclear. We aimed to determine the association of high preoperative pain catastrophizing with CPHP development and functional impairment 4 months after surgery.Patients and methodsSecondary analysis of a prospective cohort study of women undergoing abdominal/laparoscopic hysterectomy to investigate the association between high pain catastrophizing (pain catastrophizing scale, PCS≥20) with CPHP and associated functional impairment (defined as impairment with standing for ≥30 minutes, sitting for ≥30 minutes, or walking up or down stairs). CPHP and functional impairment were assessed via 4- and 6-month phone surveys.ResultsOf 216 patients, 72 (33.3%) had high PCS, with mean (SD) of 30.0 (7.9). In contrast, 144 (66.7%) patients had low PCS, with mean (SD) of 9.0 (4.7). At 4 months, 26/63 (41.3%) patients in the high PCS group developed CPHP, compared to 24/109 (22.0%) in the low PCS group. At 6 months, 14/53 (26.4%) high PCS patients developed CPHP, compared to 10/97 (10.3%) patients with low PCS. High PCS was independently associated with CPHP at 4 months (OR 2.49 [95% CI 1.27 to 4.89], p=0.0082) and 6 months (OR 3.12 [95% CI 1.28 to 7.64], p=0.0126) but was not associated with functional impairment. High PCS≥20, presence of evoked mechanical temporal summation (MTS), and history of abdominal/pelvic surgery predict CPHP at 4 months with area under the curve (AUC) of 0.69. Similarly, PCS≥20 and increasing MTS magnitude predicted CPHP at 6 months with AUC of 0.76.ConclusionHigh PCS was independently associated with CPHP. Future studies should identify other CPHP associated factors to formulate a risk-prediction model and investigate the effectiveness of early intervention for pain catastrophizers in improving pain-related outcomes.

Project description:IntroductionCattle temperament is an important factor that affects the profitability of beef cattle enterprises, due to its relationship with productivity traits, animal welfare and labor safety. Temperament is a complex phenotype often assessed by measuring a series of behavioral traits, which result from the effects of multiple environmental and genetic factors, and their interactions. The aims of this study were to perform a genome-wide association study and detect genomic regions, potential candidate genes and their biological mechanisms underlying temperament, measured by flight speed (FS) test in Nellore cattle.Materials and methodsThe genome-wide association study (GWAS) was performed using a single-step procedure (ssGBLUP) which combined simultaneously all 16,600 phenotypes from genotyped and non-genotyped animals, full pedigree information of 162,645 animals and 1,384 genotyped animals in one step. The animals were genotyped with High Density Bovine SNP BeadChip which contains 777,962 SNP markers. After quality control (QC) a total of 455,374 SNPs remained.ResultsHeritability estimated for FS was 0.21 ± 0.02. Consecutive SNPs explaining 1% or more of the total additive genetic variance were considered as windows associated with FS. Nine candidate regions located on eight different Bos taurus chromosomes (BTA) (1 at 73 Mb, 2 at 65 Mb, 5 at 22 Mb and 119 Mb, 9 at 98 Mb, 11 at 67 Mb, 15 at 16 Mb, 17 at 63 Kb, and 26 at 47 Mb) were identified. The candidate genes identified in these regions were NCKAP5 (BTA2), PARK2 (BTA9), ANTXR1 (BTA11), GUCY1A2 (BTA15), CPE (BTA17) and DOCK1 (BTA26). Among these genes PARK2, GUCY1A2, CPE and DOCK1 are related to dopaminergic system, memory formation, biosynthesis of peptide hormone and neurotransmitter and brain development, respectively.ConclusionsOur findings allowed us to identify nine genomic regions (SNP windows) associated with beef cattle temperament, measured by FS test. Within these windows, six promising candidate genes and their biological functions were identified. These results may contribute to a better comprehension into the genetic control of temperament expression in Nellore cattle.

Dataset Information

The association between genome-wide polymorphisms and chronic postoperative pain: a prospective observational study.

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The association between genome-wide polymorphisms and chronic postoperative pain: a prospective observational study.

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