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

Fernanda de Toledo Gonçalves, Kevin Pacheco-Barrios, Ingrid Rebello-Sanchez, Luis Castelo-Branco, Paulo S. de Melo, Joao Parente, Alejandra Cardenas-Rojas, Isabela Firigato, Anne Victorio Pessotto, Marta Imamura, Marcel Simis, Linamara Battistella, Felipe Fregni

Research output: Contribution to journalArticlepeer-review

Abstract

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. 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 analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics 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 rehabilitation (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 intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical 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.

Original languageEnglish
Article number100330
JournalInternational Journal of Clinical and Health Psychology
Volume23
Issue number1
DOIs
StatePublished - 1 Jan 2023

Keywords

  • Chronic pain
  • Cortical excitability
  • Osteoarthritis
  • Polymorphism

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