Neuropeptide Y tonically inhibits an NMDAR➔AC1➔TRPA1/TRPV1 mechanism of the affective dimension of chronic neuropathic pain.

Neuropeptides
Weisi FuBradley K Taylor

Abstract

Transection of the sural and common peroneal branches of the sciatic nerve produces cutaneous hypersensitivity at the tibial innervation territory of the mouse hindpaw that resolves within a few weeks. We report that interruption of endogenous neuropeptide Y (NPY) signaling during remission, with either conditional NPY knockdown in NPYtet/tet mice or intrathecal administration of the Y1 receptor antagonist BIBO3304, reinstated hypersensitivity. These data indicate that nerve injury establishes a long-lasting latent sensitization of spinal nociceptive neurons that is masked by spinal NPY-Y1 neurotransmission. To determine whether this mechanism extends beyond the sensory component of nociception, we used conditioned place aversion and preference assays to evaluate the affective component of pain. We found that BIBO3304 produced place aversion in mice when administered during remission. Furthermore, the analgesic drug gabapentin produced place preference after NPY knockdown in NPYtet/tet but not control mice. We then used pharmacological agents and deletion mutant mice to investigate the cellular mechanisms of neuropathic latent sensitization. BIBO3304-induced reinstatement of mechanical hypersensitivity and conditioned place ave...Continue Reading

Citations

May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Takahiro KochiNorimitsu Morioka
Oct 27, 2021·Physiological Reviews·Katrina F OstromRennolds S Ostrom

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