Sound induces analgesia through corticothalamic circuits

Sound—including music and noise—can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACx Glu ) to the thalamic posterior (PO) and ventral posterior (VP) nuclei. Optogenetic or chemogenetic inhibition of the ACx Glu →PO and ACx Glu →VP circuits mimicked the low-SNR sound–induced analgesia in inflamed hindpaws and forepaws, respectively. Artificial activation of these two circuits abolished the sound-induced analgesia. Our study reveals the corticothalamic circuits underlying sound-promoted analgesia by deciphering the role of the auditory system in pain processing.