A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli.

Abstract

Spinal projection neurons (SPNs) relay somatosensory information to the brain, yet how molecularly defined SPN subsets transmit noxious mechanical signals to drive nocifensive behaviors remains unclear. Here, we identify <i>Sncg</i>-expressing SPNs (<i>Sncg⁺</i> SPNs) that convey noxious mechanical signals through a spinoreticular ascending pathway. Using intersectional genetics, anatomical tracing, and pathway-specific manipulations in mice, we show that <i>Sncg⁺</i> SPNs project predominantly to the parabrachial nucleus and the lateral reticular nucleus (LRN). Functional analyses reveal that <i>Sncg⁺</i> spinoreticular pathway transmits noxious mechanical information. LRN neurons receiving <i>Sncg</i>⁺ spinal input are required for nocifensive behaviors elicited by noxious mechanical stimulation and contribute to mechanical allodynia of neuropathic pain. Monosynaptic tracing identifies local interneurons innervating <i>Sncg</i>⁺ SPNs, providing a substrate for spinal gating of ascending mechanical signals. These findings highlight a spinoreticular circuit involving the LRN that is essential for nocifensive behaviors to noxious mechanical stimuli.