How sound induces pain relief in mice

New research in mice demonstrates that pain relief by sound is not purely attributable to stress reduction and distraction; the study reveals a neural circuit underlying sound-induced analgesia in the mouse brain. While the mechanisms underlying similarly observed music-induced pain relief in humans are likely more complicated than those in mice, the findings could inspire the development of future pain management interventions. Sound, including music and noise, is known to have a pain-relieving effect on humans. Its analgesic effect during dental operations was first reported more than 50 years ago and has since been leveraged as an intervention to alleviate postoperative and procedural pain in clinical settings. It is also increasingly being tested as a therapy for chronic pain disorders. Because different types of music and sounds can relieve pain equally in different individuals, the inherent characteristics of music or other contextual factors – not just the music per se – are thought to drive these pain-relieving effects. However, the underlying neural mechanisms remain unknown. Inspired by observations in humans, Wenjie Zhou and colleagues evaluated the phenomenon in mice with inflammatory pain induced by hindpaw injection of complete Freund’s adjuvant. Using a suite of methods, including behavioral tests, viral tracing, microendoscopic calcium imaging, and multielectrode recordings, Zhou et al. discovered that sounds with a low-signal to ambient noise ratio (SNR) – specifically a 5 decibel (dB) increase in sound intensity over ambient sound levels – caused analgesia by inhibiting inputs from the auditory cortex to distinct regions of the somatosensory thalamus, depending on where the pain was administered. Furthermore, artificial manipulation of the identified circuits both mimicked and suppressed sound-induced analgesic effects. “Although this experimental paradigm is not equivalent to using music and pleasant sounds to evoke analgesia in humans, the study of Zhou et al. opens up new directions for research on sound-induced analgesia by creating a model in which the mechanistic underpinnings can be investigated,” write Rohini Kuner and Thomas Kuner in a related Perspective.