Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global dis-ability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analy-ses to compare carriers versus non-carriers in terms of clinical and neurophysiological character-istics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabili-tation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intra-cortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and corti-cal inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study assessed the association between genetic polymorphisms related to chronic pain and pain-related outcomes and neurophysiological characteristics. The results showed that patients carrying polymorphisms on OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation, and these genetic polymorphisms also affected the improvement of cortical inhibition. The findings suggest the potential role of combining genetic and neurophysiological markers in guiding the treatment response in this population.