Billens Amber, De Groote Amber, Syx Delfien, Meeus Mira, Van Oosterwijck Jessica
Spine, Head and Pain Research Unit Ghent, Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Pain in Motion International Research Consortium (www.paininmotion.be).
Pain. 2025 Oct 1;166(10):2236-2248. doi: 10.1097/j.pain.0000000000003608. Epub 2025 Jun 12.
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.
慢性肌肉骨骼疼痛（CMP）是慢性疼痛最常见的形式。通过实验性疼痛测量评估，CMP患者的一个亚组表现出疼痛处理改变，包括内源性疼痛调制受损。一种假设是，基因和/或表观遗传变异可能导致动态实验性疼痛评估结果的个体差异。因此，进行了一项系统综述，以全面总结目前关于基因和表观遗传对有或无CMP的成年人动态实验性疼痛测量影响的证据。该综述按照系统评价和Meta分析的首选报告项目指南进行。检索了四个电子数据库以确定相关研究。分别使用纽卡斯尔渥太华量表和推荐分级、评估、制定与评价方法评估偏倚风险和证据质量。共纳入24篇文章，涉及34个不同的感兴趣区域。低质量证据表明，COMT基因的rs4680单核苷酸多态性（SNP）或SLC6A基因的血清素转运体相关多态性区域SNP与健康志愿者或CMP患者的条件性疼痛调制之间无关联。此外，发现低质量证据表明OPRM1基因的rs1799971 SNP与健康志愿者的条件性疼痛调制之间缺乏关联。其他基因和表观遗传变异提供的证据有限或相互矛盾。目前，动态实验性疼痛测量似乎对基因和表观遗传变异具有较强的抗性。然而，需要更多可重复的研究，以更好地了解基因和表观遗传变异是否以及如何影响（改变）疼痛处理，这对于推进CMP人群的预防和治疗策略至关重要。
