August 30, 2012

Targeting new pathways to ease pain

The spinal cord’s neuropeptide Y signaling pathway may be a good target for new pain therapeutics.

Noxious – and potentially painful – stimuli are processed first in the dorsal horn of the spinal cord, making this region a possible target for pain therapeutics. But the organization of the dorsal horn and the precise roles of its neuronal populations are incompletely understood.


Laurie Lemons, Ph.D., and Ronald Wiley, M.D., Ph.D., investigated the role of dorsal horn neurons that respond to the signaling molecule neuropeptide Y (NPY). The researchers used a targeted toxin to selectively destroy neurons expressing the NPY receptor Y1R in rats. Then, they tested the rats’ behavioral responses – designed to require cerebral processing – to thermal and chemical pain stimuli.

They found that the loss of Y1R-expressing neurons reduced sensitivity to thermal stimuli and eliminated allodynia (pain from a non-painful stimulus – a common clinical pain-related problem), without interfering with the analgesic effects of morphine. The findings, reported in the Aug. 2 issue of Neuroscience, suggest that the spinal NPY system is an appropriate target for the development of new analgesic drugs.

This research was supported by the Department of Veterans Affairs.