Work

A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli

Year: 2026

Type: article

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 Sncg -expressing SPNs ( Sncg + 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 Sncg + SPNs project predominantly to the parabrachial nucleus and the lateral reticular nucleus (LRN). Functional analyses reveal that Sncg + spinoreticular pathway transmits noxious mechanical information. LRN neurons receiving Sncg + 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 Sncg + 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2604642123