Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Mary Free Bed Rehabilitation Spine Center, Grand Rapids, MI, USA.
Eur J Pain. 2020 Feb;24(2):398-412. doi: 10.1002/ejp.1497. Epub 2019 Nov 13.
BACKGROUND: This study examined the extent to which genetic variability modifies Transcutaneous Electrical Nerve Stimulation (TENS) effectiveness in osteoarthritic knee pain. METHODS: Seventy-five participants with knee osteoarthritis were randomly assigned to either: (a) High-frequency TENS, (b) Low-frequency TENS or (c) Transient Placebo TENS. Pain measures were collected pre- and post-treatment. Participants were genotyped on genes implicated in central or peripheral pain pathways: NGFB, NTRK1, EDNRA, EDNRB, EDN1, OPRM1, TAC1, TACR1, BDNF, BDKRB1, 5HTT, COMT, ESR2, IL6 and IL1B. Genetic association using linear regression modelling was performed separately for the transient placebo TENS subjects, and within the High-frequency TENS + Low-frequency TENS participants, including TENS level as a covariate. RESULTS: In the placebo group, SNPs rs165599 (COMT) was significantly associated with an increased heat pain threshold (β = -1.87; p = .003) and rs6827096 (EDNRA) with an increased resting pain (β = 2.68; p = .001). Within the treatment groups, TENS effectiveness was reduced by the SNP rs6537485 (EDNRA) minor allele in relationship to mechanical sensation (β = 184.13; p = 5.5E-9). Individuals with the COMT rs4680 minor allele reported lowered pain at rest after TENS (β = -42.30; p = .001), with a higher magnitude of pain reduction (28 unit difference) in the low-frequency TENS group compared to the high-frequency TENS group (β = 28.37; p = .0004). CONCLUSIONS: EDNRA and COMT are implicated in osteoarthritic knee pain and provide a basis for tailoring TENS interventions according to individual characteristics. SIGNIFICANCE: Findings from this study demonstrate that genetic variation within the COMT and EDNRA genes influences the effectiveness of TENS, a non-pharmacologic pain-reduction intervention, in the context of osteoarthritic knee pain. Evidence such as this may contribute to risk models that provide a clinically useful tool for personalizing TENS interventions according to individual characteristics in order to best control pain and maximize functional status.
背景：本研究旨在探讨基因变异性在经皮神经电刺激（TENS）治疗骨关节炎性膝关节疼痛中的作用。
方法：75 名膝关节骨关节炎患者被随机分为三组：（a）高频 TENS，（b）低频 TENS 或（c）短暂安慰剂 TENS。治疗前后分别采集疼痛测量值。对涉及中枢或外周疼痛通路的基因 NGFB、NTRK1、EDNRA、EDNRB、EDN1、OPRM1、TAC1、TACR1、BDNF、BDKRB1、5HTT、COMT、ESR2、IL6 和 IL1B 进行基因分型。对短暂安慰剂 TENS 受试者进行线性回归模型的遗传关联分析，并对高频 TENS+低频 TENS 参与者进行分析，包括 TENS 水平作为协变量。
结果：在安慰剂组中，SNP rs165599（COMT）与热痛阈值增加显著相关（β=-1.87；p=.003），SNP rs6827096（EDNRA）与静息痛增加显著相关（β=2.68；p=.001）。在治疗组中，SNP rs6537485（EDNRA）的次要等位基因与机械感觉相关，TENS 效果降低（β=184.13；p=5.5E-9）。COMT rs4680 次要等位基因携带者在 TENS 后静息痛减轻（β=-42.30；p=.001），低频 TENS 组比高频 TENS 组的疼痛缓解幅度更大（28 单位差异）（β=28.37；p=.0004）。
结论：EDNRA 和 COMT 与骨关节炎性膝关节疼痛有关，为根据个体特征定制 TENS 干预提供了依据。
意义：本研究结果表明，COMT 和 EDNRA 基因内的遗传变异影响 TENS（一种非药物性止痛干预措施）在骨关节炎性膝关节疼痛中的有效性。这样的证据可能有助于风险模型的建立，为根据个体特征对 TENS 干预进行个性化定制提供一种有用的临床工具，以最佳控制疼痛并最大限度地提高功能状态。
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