GATING OF SPINAL NOCICEPTIVE TRANSMISSION THROUGH THE DESCENDING S1HL CORTICOSPINAL TRACT

Evidence suggests that the primary somatosensory cortex (S1) plays a significant role in encoding sensory components of nociception, and recent work has unravelled cortical layer-specific contributions. Here, we aim to characterize the role of the layer 5 pyramidal tract (PT) of the hindlimb S1 (S1HL) in nociception, with a focus on its monosynaptic targeting of the lumbar dorsal horn of the spinal cord (PT–LDH tract). We use viral approaches for anatomical tracing and optogenetic or chemogenetic manipulation of PT neurons or their postsynaptic LDH targets, combined with in vivo extracellular electrophysiological recordings and behavioural assays.
We report that stimulation of the PT–LDH tract reduced mechanical hyperalgesia and elicited a conditioned place preference in the complete Freund’s adjuvant (CFA) model of inflammatory pain; these effects were replicated upon specific stimulation of postsynaptic LDH target neurons. In situ hybridisation revealed that PAX2-, GlyT2-, and pENK-expressing neurons accounted for a majority of these neuronal targets. Spinal electrophysiological recordings showed that PT–LDH stimulation selectively reduced C-type late responses in wide-dynamic-range (WDR) neurons while preserving A-type early responses, indicating fibre-type-specific modulation. Finally, recordings in S1HL revealed that PT–LDH neurons respond to both noxious and non-noxious peripheral input and can encode pain prediction.
Overall, we interpret the PT–LDH tract as a participant in descending inhibitory control of nociception, complimenting other classical forms of descending control. Future work will further elucidate its impact on ascending tactile and nociceptive information.