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Papers of the Week


Papers: 5 Nov 2022 - 11 Nov 2022


Animal Studies, Pharmacology/Drug Development


2022 Nov 16


Proc Natl Acad Sci U S A


119


46

Editor's Pick

Spinal neuropeptide Y Y1 receptor-expressing neurons are a pharmacotherapeutic target for the alleviation of neuropathic pain.

Authors

Nelson TS, Sinha GP, Santos DFS, Jukkola P, Prasoon P, Winter MK, McCarson KE, Smith BN, Taylor BK
Proc Natl Acad Sci U S A. 2022 Nov 16; 119(46):e2204515119.
PMID: 36343228.

Abstract

Peripheral nerve injury sensitizes a complex network of spinal cord dorsal horn (DH) neurons to produce allodynia and neuropathic pain. The identification of a druggable target within this network has remained elusive, but a promising candidate is the neuropeptide Y (NPY) Y1 receptor-expressing interneuron (Y1-IN) population. We report that spared nerve injury (SNI) enhanced the excitability of Y1-INs and elicited allodynia (mechanical and cold hypersensitivity) and affective pain. Similarly, chemogenetic or optogenetic activation of Y1-INs in uninjured mice elicited behavioral signs of spontaneous, allodynic, and affective pain. SNI-induced allodynia was reduced by chemogenetic inhibition of Y1-INs, or intrathecal administration of a Y1-selective agonist. Conditional deletion of in DH neurons, but not peripheral afferent neurons prevented the anti-hyperalgesic effects of the intrathecal Y1 agonist. We conclude that spinal Y1-INs are necessary and sufficient for the behavioral symptoms of neuropathic pain and represent a promising target for future pharmacotherapeutic development of Y1 agonists.