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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



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


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.


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.