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.
Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPL
Glu
) exhibited significantly elevated burst firing accompanied by upregulation of Ca
v
3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HL
Glu
) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HL
Glu
neuronal activity during RIH. Moreover, preoperative suppression of Ca
v
3.1-dependent burst firing in VPL
Glu
neurons or chemogenetic inhibition of VPL
Glu
neuronal terminals in the S1HL abolished the increased S1HL
Glu
neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPL
Glu
neurons to activate S1HL
Glu
neurons, thus revealing an ion channel–mediated neural circuit basis for RIH that can guide analgesic development.
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