WE examined the expression of preproenkephalin mRNA in pain-modulating
regions of the rat's brainstem using in situ hybridization histochemi
stry. We found that neurones in the Kolliker-Fuse nucleus, which recei
ves projections from spinal nociceptive-specific cells, express enkeph
alin mRNA, that this expression is increased by noxious pinch applied
to the skin of awake animals, and that these enkephalinergic neurones
are part of a descending system that terminates in the rostroventral m
edulla and the spinal cord. These findings show that natural noxious s
timuli activate opioidergic bulbospinal neurones that could directly m
odulate spinal nociceptive transmission.