Vanderbilt University School of Nursing, Nashville, Tennessee.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt Genetics Institute, Nashville, Tennessee.
J Pain. 2023 Jun;24(6):1056-1068. doi: 10.1016/j.jpain.2023.01.018. Epub 2023 Feb 3.
Chronic overlapping pain conditions (COPCs) are believed to share common etiological mechanisms involving central sensitization. Genetic and environmental factors putatively combine to influence susceptibility to central sensitization and COPCs. This study employed a genome-wide polygenic risk score approach to evaluate genetic influences on 8 common COPCs. COPCs were identified by International Classification of Disease codes in Vanderbilt's deidentified clinical biorepository (BioVU), with each COPC condition empirically weighted for the level of central sensitization based on prior work. A centralized pain score (CPS) was calculated for 55,340 individuals by summing the weighted number of COPCs. Overall, 12,502 individuals (22.6%) were diagnosed with at least 1 COPC, with females exhibiting nearly twice the mean CPS as males. To assess the genetic influence on centralized pain in COPCs, 6 pain polygenic risk scores (PRSs) were developed using UK Biobank data to predict 6 pain criteria (no pain, neck/shoulder, abdomen, hip, knee, low back pain). These PRSs were then deployed in the BioVU cohort to test for association with CPS. In regression models adjusted for age, sex, and BMI, all pain PRSs except hip pain were significantly associated with CPS. Our findings support a shared polygenic influence across COPCs potentially involving central sensitization mechanisms. PERSPECTIVE: This study used a polygenic risk score approach to investigate genetic influences on chronic overlapping pain conditions. Significant findings in this study provide evidence supporting previous hypotheses that a shared polygenic influence involving central sensitization may underly chronic overlapping pain conditions and can guide future biomarker and risk assessment research.
慢性重叠疼痛病症（COPCs）被认为具有共同的发病机制，涉及中枢敏化。遗传和环境因素推测结合起来影响中枢敏化和 COPCs 的易感性。本研究采用全基因组多基因风险评分方法评估遗传对 8 种常见 COPCs 的影响。COPCs 通过范德比尔特大学匿名临床生物库（BioVU）中的国际疾病分类代码确定，根据先前的工作，每种 COPC 病症都根据中枢敏化的程度进行了经验加权。通过将加权后的 COPC 数量相加，为 55340 个人计算了一个集中疼痛评分（CPS）。总体而言，12502 个人（22.6%）被诊断出至少有一种 COPC，女性的平均 CPS 几乎是男性的两倍。为了评估遗传对 COPC 集中疼痛的影响，使用英国生物库数据开发了 6 个疼痛多基因风险评分（PRS）来预测 6 个疼痛标准（无痛、颈部/肩部、腹部、臀部、膝盖、腰痛）。然后将这些 PRS 部署在 BioVU 队列中，以测试与 CPS 的关联。在调整年龄、性别和 BMI 的回归模型中，除了臀部疼痛外，所有疼痛 PRS 都与 CPS 显著相关。我们的研究结果支持 COPC 之间存在共同的多基因影响，可能涉及中枢敏化机制。观点：本研究采用多基因风险评分方法研究遗传对慢性重叠疼痛病症的影响。本研究中的显著发现为先前的假设提供了证据，即涉及中枢敏化的共同多基因影响可能是慢性重叠疼痛病症的基础，并为未来的生物标志物和风险评估研究提供指导。
