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

Abstract

1Chronic pain is a debilitating disease that is usually comorbid to anxiety and depression. Current treatment approaches primarily rely on analgesics, but they often neglect emotional aspects. Non-pharmacological interventions have been incorporated into clinics to provide a more comprehensive management of chronic pain. Among these interventions, listening to music is a well-accepted and cost-effective option. However, the underlying mechanisms of music-mediated pain relief remain insufficiently understood. Here, our aim was to evaluate the effects of music exposure in an animal model of chronic pain. First, we injected mice with the inflammatory agent complete Freunds adjuvant (CFA) into the hind paw and housed them for 14 days with background music during their active period (Mozart K.205, overnight), or silence. The impact of music exposure on nociception and anxiety-like and depression-like behaviors was evaluated through different paradigms, including the hot plate, Von Frey, elevated plus maze, splash, and tail suspension tests. Additionally, we investigated whether music influences dopamine dynamics in the nucleus accumbens (NAcc), a pivotal region involved in pain processing, anhedonia, and reward. Our findings indicate that music exposure prevents the decreased NAcc activity observed in CFA-injected mice, linking with a sex-dependent reduction of allodynia, anxiety- and depression-like behaviors. Thus, females were more sensitive to music exposure. Collectively, our findings provide compelling evidence for the integration of music listening as a non-pharmacological intervention in chronic pain conditions. Moreover, the observed impact on the NAcc suggests its potential as a therapeutic target for addressing chronic pain and its associated symptoms.