Tonic inhibition of chronic pain by neuropeptide Y

Brian Solway, Soma C. Bose, Gregory Corder, Renee R. Donahue, Bradley K. Taylor

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npytet/tet) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity. Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase. Taken together, these data establish spinal NPY receptor systems as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain. NPY and its receptors appear to be part of a mechanism whereby mammals naturally recover from the hyperalgesia associated with inflammation or nerve injury.

Original languageEnglish (US)
Pages (from-to)7224-7229
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number17
DOIs
StatePublished - Apr 26 2011

Keywords

  • Allodynia
  • BIBO3304
  • BIIE0246
  • Neuropathic

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