George Steven Z, Wallace Margaret R, Wu Samuel S, Moser Michael W, Wright Thomas W, Farmer Kevin W, Borsa Paul A, Parr Jeffrey J, Greenfield Warren H, Dai Yunfeng, Li Hua, Fillingim Roger B
Department of Physical Therapy, University of Florida, Gainesville, FL, USA Department of Molecular Genetics and Microbiology and UF Genetics Institute, University of Florida, Gainesville, FL, USA Departments of Biostatistics Orthopaedics and Rehabilitation, and Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA.
Pain. 2015 Jan;156(1):148-156. doi: 10.1016/j.pain.0000000000000012.
Tailored treatment based on individual risk factors is an area with promise to improve options for pain relief. Musculoskeletal pain has a biopsychosocial nature, and multiple factors should be considered when determining risk for chronic pain. This study investigated whether subgroups comprised genetic and psychological factors predicted outcomes in preclinical and clinical models of shoulder pain. Classification and regression tree analysis was performed for an exercise-induced shoulder injury cohort (n = 190) to identify high-risk subgroups, and a surgical pain cohort (n = 150) was used for risk validation. Questionnaires for fear of pain and pain catastrophizing were administered before injury and preoperatively. DNA collected from saliva was genotyped for a priori selected genes involved with pain modulation (COMT and AVPR1A) and inflammation (IL1B and TNF/LTA). Recovery was operationalized as a brief pain inventory rating of 0/10 for current pain intensity and <2/10 for worst pain intensity. Follow-up for the preclinical cohort was in daily increments, whereas follow-up for the clinical cohort was at 3, 6, and 12 months postoperatively. Risk subgroups comprised the COMT high pain sensitivity variant and either pain catastrophizing or fear of pain were predictive of heightened shoulder pain responses in the preclinical model. Further analysis in the clinical model identified the COMT high pain sensitivity variant and pain catastrophizing subgroup as the better predictor. Future studies will determine whether these findings can be replicated in other anatomical regions and whether personalized medicine strategies can be developed for this risk subgroup.
基于个体风险因素的个性化治疗是一个有望改善疼痛缓解选择的领域。肌肉骨骼疼痛具有生物心理社会性质，在确定慢性疼痛风险时应考虑多个因素。本研究调查了由遗传和心理因素组成的亚组是否能预测肩部疼痛临床前和临床模型的结果。对运动诱发的肩部损伤队列（n = 190）进行分类和回归树分析以识别高风险亚组，并使用手术疼痛队列（n = 150）进行风险验证。在受伤前和术前发放疼痛恐惧和疼痛灾难化问卷。从唾液中收集的DNA对预先选择的与疼痛调节（COMT和AVPR1A）和炎症（IL1B和TNF/LTA）相关的基因进行基因分型。恢复情况通过当前疼痛强度的简短疼痛量表评分为0/10且最严重疼痛强度<2/10来衡量。临床前队列的随访按日递增，而临床队列的随访在术后3、6和12个月进行。风险亚组包括COMT高疼痛敏感性变体以及疼痛灾难化或疼痛恐惧，这些在临床前模型中可预测肩部疼痛反应增强。临床模型中的进一步分析确定COMT高疼痛敏感性变体和疼痛灾难化亚组为更好的预测指标。未来的研究将确定这些发现是否能在其他解剖区域得到重复，以及是否可以为这个风险亚组制定个性化医疗策略。
