Dopamine dynamics in chronic pain: music-induced, sex-dependent, behavioral effects in mice.

Introduction: Chronic pain is a debilitating disease that is usually comorbid to anxiety and depression. Current treatment approaches mainly rely on analgesics but often neglect emotional aspects. Nonpharmacological interventions, such as listening to music, have been incorporated into clinics to provide a more comprehensive management of chronic pain. However, the underlying mechanisms of music-mediated pain relief are not fully understood. Objectives: Our aim was to evaluate the effects and mechanisms of music exposure in an animal model of chronic pain. Methods: We injected mice with the complete Freund adjuvant (CFA) inflammatory agent into the hind paw and housed them for 14 days with background music, or ambient noise, during their active period (Mozart K.205, overnight). The effect of music exposure on nociception, anxiety-like behaviors, and depression-like behaviors was evaluated through different paradigms, including the hot plate, Von Frey, elevated plus maze, splash, and tail suspension tests. In addition, we conducted fiber photometry experiments to investigate whether music influences dopamine dynamics in the nucleus accumbens (NAcc), a crucial region involved in pain processing, anhedonia, and reward. Results: Our findings indicate that music exposure prevents the decrease in NAcc activity observed in CFA-injected mice, linking with a sex-dependent reduction in allodynia, anxiety-like behaviors, and depression-like behaviors. Accordingly, female mice were more sensitive to music exposure than male mice. Conclusion: Collectively, our findings provide compelling evidence for the integration of music as a nonpharmacological intervention in chronic pain conditions. Moreover, the observed effect on NAcc suggests its potential as a therapeutic target for addressing chronic pain and its associated symptoms.