The influence of genetic and epigenetic variations on dynamic experimental pain measures in adults with and without chronic musculoskeletal pain: a systematic review.

Abstract

Chronic musculoskeletal pain (CMP) is the most prevalent form of chronic pain. A subgroup of patients with CMP shows altered pain processing, including impaired endogenous pain modulation, as evaluated by experimental pain measures. One hypothesis is that genetic and/or epigenetic variants may contribute to individual differences in outcomes of dynamic experimental pain assessment. Therefore, a systematic review was performed to comprehensively summarize the current evidence regarding genetic and epigenetic influences on dynamic experimental pain measures in adults with and without CMP. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four electronic databases were searched to identify relevant studies. Risk of bias and quality of evidence were assessed using the Newcastle Ottawa Scale and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. A total of 24 articles were included, accounting for 34 different regions of interest. Low-quality evidence indicated no association between the rs4680 single-nucleotide polymorphism (SNP) of the COMT gene or the serotonin-transporter-linked polymorphic region SNP of the SLC6A gene and conditioned pain modulation in healthy volunteers or in patients with CMP. In addition, low-quality evidence was found for the lack of an association between the rs1799971 SNP of the OPRM1 gene and conditioned pain modulation in healthy volunteers. Other genetic and epigenetic variants provided limited or conflicting evidence. For now, it seems that dynamic experimental pain measurements are robust to genetic and epigenetic variations. However, more reproducible research is warranted to better understand whether or not and how genetic and epigenetic variations influence (altered) pain processing, which is crucial for advancing both preventive and therapeutic strategies in CMP populations.