Genetic polymorphisms and prediction of chronic post‐surgical pain after hysterectomy—a subgroup analysis of a multicenter cohort study

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background: Chronic post-surgical pain (CPSP) is a serious problem. Clinical and psychological variables have not been able to explain all observed variance in prevalence and severity of CPSP. The first objective is to determine the association between genetic polymorphisms and the prevalence of CPSP after hysterectomy. The second objective is to analyze if the implementation of genetic polymorphisms into a previously performed clinical and psychological predictor analysis on the development of CPSP after hysterectomy will improve its discriminatory power.Methods: A prospective multicenter cohort study was performed in patients undergoing hysterectomy for benign indication. Clinical and psychological variables were collected by questionnaires in the week before surgery, post-operatively up to day 4, 3 and 12 months after hysterectomy. Blood was collected and 16 polymorphisms previously suggested to be correlated to CPSP (COMT, GCH1, KCNS1, CACNG2, and OPRM1) were genotyped. Logistic regression analyses were performed.Results: Three hundred and forty-five patients were available for the genetic analyses. The prevalence of CPSP 3 months post-operatively was 10.5% and after 12 months 7.9%. The polymorphism rs4818 within the COMT gene was associated with the prevalence of CPSP after 3 months. No polymorphisms were associated with CPSP after 12 months. The addition of rs4818 to the prediction model did not change its discriminatory power significantly. Conclusion:The rs4818 polymorphism within the COMT gene was associated with the prevalence of CPSP 3 months after hysterectomy, but the implementation of rs4818 into the prediction model did not significantly improve the chance of identifying hysterectomy patients at risk for CPSP.

<p>A Conceptual Model of Biopsychosocial Mechanisms of Transition from Acute to Chronic Postsurgical Pain in Children and Adolescents</p>

“…29 A large body of adult perioperative literature points to the role of the catechol-O-methyltransferase (COMT) gene in modulating pain sensitivity and the incidence of chronic pain. [30][31][32][33][34] One pediatric study found significant relationships between three COMT SNPs and acute postsurgical pain intensity, 35 suggesting a potential role in interindividual variation in postoperative pain perception. Two studies investigated the association between DNA methylation in…”

Dopaminergic neurotransmission and genetic variation in chronification of post-surgical pain

“…It has been shown that the addition of a single polymorphism (SNP rs4818 in COMT) to a prediction model of CPSP enhanced, although not significantly, the prediction power from 78% to 82%. 150…”

Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain

“…In diabetes and prostate cancer, the predictive accuracy is higher than the currently available clinical models [70]. A recent clinical prediction model on CPSP increased the predictive power of by including a single SNP into the prediction model [7]. This increase in predictive power was not significant but including a complete PRS into the prediction model would significantly improve the clinical prediction modelling [52,62,69,71].…”

“…age, biological sex) and psychological (e.g. anxiety) risk factors of CPSP can account for 78% of the variance in the development of CPSP [7,8]. Although recent evidence (both GWAS and gene-Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10048-020-00614-5) contains supplementary material, which is available to authorized users.…”