Pain Alleviation through Rag Bhairavi (15dB, Flute): Activation of the Hypothalamus-pituitary Axis and β-endorphin–cAMP Pathway in Swiss Albino Mice

Objectives: Music, as a form of entertainment, has been shown to reduce stress and anxiety by stimulating the release of various neurotransmitters. β-Endorphin, a natural pain-relieving peptide released in response to noxious stimuli, alleviates pain by inhibiting cyclic AMP (cAMP) through the activation of the μ-opioid receptor. This study aims to explore the anti-nociceptive effects of pain alleviation through music and investigate its potential underlying mechanisms using different pain models. Methods: The anti-nociceptive efficacy of pain alleviation through music, specifically Rag Bhairavi played on the flute at 15 dB (RBM), was evaluated in Swiss albino mice, alongside paracetamol (100 mg/kg) as a standard analgesic control. Both central and peripheral pain models were employed to assess the effects of RBM on pain. Additionally, the influence of RBM on non-painful stimuli was examined. To investigate the correlation between RBM and neurotransmitter levels (norepinephrine, dopamine, serotonin, and β-endorphin), brain homogenates from treated animals were analyzed. The potential mechanism of pain reduction was further explored through Western blot analysis, focusing on cytosolic cAMP levels. Results: Pain alleviation through music with RBM significantly elevated the levels of key neurotransmitters in the brain. Moreover, western blot analysis revealed a marked reduction in cAMP levels in the RBM-treated group compared to the pain-induced group. These findings suggest that RBM exerts its pain-relieving effects by enhancing the release of hypothalamic-pituitary neurochemicals, particularly β-endorphin, and reducing cAMP levels through activation of the μ-opioid receptor. Conclusion: The study concludes that Rag Bhairavi pain alleviation through music exhibits significant anti-nociceptive properties, likely mediated by an increase in neurochemical levels and inhibition of cAMP via β-endorphin-dependent activation of the μ-opioid receptor.