Music impact on dopamine dynamics upon opioid-based treatment for chronic pain

Chronic pain is a major concern in public health. Opioids are effective analgesics, but they may lead to severe adverse effects, including dependence. Non-pharmacological interventions, such as music listening, can be used as adjuvants to analgesics. However, the underlying mechanisms are insufficiently understood. Here, we aimed at assessing whether music exposure can modulate opioid adverse effects by influencing dopamine dynamics in the brain. First, mice underwent surgery to inject a dopamine biosensor (Dlight 1.3b) and to implant a fiberoptic in the nucleus accumbens (NAcc). After allowing biosensor expression for 1 month, mice were unilaterally injected in the hind paw with complete Freund’s adjuvant (CFA) and housed for 14 days with background music during their active period (Mozart K.205, overnight), or silence. In addition, following 9 days post-CFA injection, mice also received repeated morphine administration (10 mg/kg, twice a day, five days). We assessed the effects of music intervention on dopamine dynamics using fiber photometry while mice performed an operant behavior task (i.e. food self-administration), which can be affected by opioid dependence. Our data indicate that music restored the frequency of spontaneous dopamine transients in the NAcc induced by chronic pain. Additionally, music exposure modulated food-induced dopamine release, which was altered upon chronic morphine treatment. Collectively, our findings provide compelling evidence for the integration of music-based therapies as a non-pharmacological intervention for chronic pain treatment.