George Steven Z, Wu Samuel S, Wallace Margaret R, Moser Michael W, Wright Thomas W, Farmer Kevin W, Greenfield Warren H, Dai Yunfeng, Li Hua, Fillingim Roger B
University of Florida, Gainesville.
University of Florida Genetics Institute, University of Florida, Gainesville.
Arthritis Care Res (Hoboken). 2016 Nov;68(11):1671-1680. doi: 10.1002/acr.22876. Epub 2016 Oct 6.
To identify novel combinations of genetic and psychological factors that predicted 12-month postoperative pain and disability outcomes following arthroscopic shoulder surgery.
A prospective presurgical cohort (n = 150) was recruited to complete validated psychological questionnaires and have their DNA collected from saliva. DNA was genotyped for a priori selected genes involved with pain modulation (ADRB2, OPRM1, AVPR1A, GCH1, and KCNS1) and inflammation (IL1B, TNF/LTA, and IL6). The outcome measures of interest were the Brief Pain Inventory and Disabilities of the Arm, Shoulder, and Hand questionnaire. Followup for the cohort was at 3, 6, and 12 months postoperatively. After controlling for age, sex, race, and preoperative status, genetic and psychological factors were entered as main effects and interaction terms in separate general linear models for predicting postoperative pain and disability outcomes.
Seven interactions involving pain-modulatory genes were identified. Three provided strong statistical evidence for different outcomes, including KCNS1 and kinesiophobia for preoperative pain intensity, ADRB2 and depressive symptoms for postoperative course, and GCH1 and anxiety symptoms for 12-month pain-intensity outcome. Ten interactions involving inflammatory genes were identified. Three provided strong statistical evidence for the 12-month postoperative course outcome, including 2 different IL6 single-nucleotide polymorphism and pain catastrophizing, and IL6 and depressive symptoms.
The current study identified novel genetic and psychological interactions that can be used in future studies to further understand the development of persistent postoperative pain and investigate the effectiveness of tailored treatment.
确定可预测关节镜下肩部手术后12个月疼痛和功能障碍结局的遗传因素与心理因素的新组合。
招募了一个前瞻性术前队列（n = 150），以完成经过验证的心理问卷，并从唾液中收集其DNA。对与疼痛调节（ADRB2、OPRM1、AVPR1A、GCH1和KCNS1）及炎症（IL1B、TNF/LTA和IL6）相关的预先选定基因进行DNA基因分型。感兴趣的结局指标为简明疼痛量表和手臂、肩部和手部功能障碍问卷。对该队列在术后3个月、6个月和12个月进行随访。在控制年龄、性别、种族和术前状态后，将遗传因素和心理因素作为主效应和交互项纳入单独的一般线性模型，以预测术后疼痛和功能障碍结局。
确定了7种涉及疼痛调节基因的相互作用。其中3种为不同结局提供了强有力的统计学证据，包括KCNS1与术前疼痛强度的运动恐惧、ADRB2与术后病程的抑郁症状，以及GCH1与12个月疼痛强度结局的焦虑症状。确定了10种涉及炎症基因的相互作用。其中3种为术后12个月病程结局提供了强有力的统计学证据，包括2种不同的IL6单核苷酸多态性与疼痛灾难化，以及IL6与抑郁症状。
本研究确定了新的遗传和心理相互作用，可用于未来研究，以进一步了解持续性术后疼痛的发生发展，并研究针对性治疗的有效性。
