OPRM1 and BDNF polymorphisms associated with a compensatory neurophysiologic signature in knee osteoarthritis patients.

Objective: The present study investigated the relationship between three genetic polymorphisms of OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) and EEG-measured brain oscillations in Knee Osteoarthritis (KOA) patients.

Materials And Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), KOA arm, with 66 patients, considering demographic (age, sex, and education), clinical (pain intensity and duration), OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) genotypes, and electrophysiological measures. Brain oscillations relative power from Delta, Theta, Alpha, Low Alpha, High Alpha, Beta, Low Beta and High Beta oscillations were measured during resting state EEG. Multivariate regression models were used to explore the main brain oscillation predictors of the three genetic polymorphisms.

Results: Our findings demonstrate that Theta and Low Beta oscillations are associated with the variant allele of OPRM1-rs1799971 (A118G) on left frontal and left central regions, respectively, while Alpha brain oscillation is associated with variant genotypes (CT/TT) of BDNF-rs6265 on frontal (decrease of oscillation power) and left central (increase of oscillation power) regions. No significant model was found for OPRM1-rs1799972 (C17T) in addition to the inclusion of pain intensity as a significant predictor of this last model.

Conclusion: One potential interpretation for these findings is that polymorphisms of OPRM1 - that is involved with endogenous pain control - lead to increased compensatory oscillatory mechanisms, characterized by increased theta oscillations. Along the same line, polymorphisms of the BDNF lead to decreased alpha oscillations in the frontal area, likely also reflecting the disruption of resting states to also compensate for the increased injury associated with knee OA. It is possible that these polymorphisms require additional brain adaption to the knee OA related injury.