• Manika Govil, Nandita Mukhopadhyay, Teri Holwerda, Kathleen Sluka, Barbara Rakel, and Debra L Schutte.
• Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
• Eur J Pain. 2020 Feb 1; 24 (2): 398-412.

BackgroundThis study examined the extent to which genetic variability modifies Transcutaneous Electrical Nerve Stimulation (TENS) effectiveness in osteoarthritic knee pain.MethodsSeventy-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.ResultsIn 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).ConclusionsEDNRA and COMT are implicated in osteoarthritic knee pain and provide a basis for tailoring TENS interventions according to individual characteristics.SignificanceFindings 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.© 2019 European Pain Federation - EFIC®.

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