NPY2R signaling gates spontaneous and mechanical, but not thermal, pain transmission

Sihan Chen, Xian Yu Liu, Yingfu Jiao, Zhou Feng Chen, Weifeng Yu

Research output: Contribution to journalArticle

2 Scopus citations


Neuropeptide Y signaling plays an important role in inhibiting chronic pain in the spinal cord of mice. However, little is known about the respective roles of two major neuropeptide Y receptors, Y1R and Y2R, in evoked and spontaneous pain behavior under normal physiological condition. Using intrathecal administration approach, we found that pharmacological inhibition of Y2R, unexpectedly, gave rise to spontaneous pain behavior. In addition, Y2R antagonism also resulted in long-lasting mechanical but not thermal hypersensitivity. By contrast, neither overt spontaneous pain behavior nor mechanical and thermal hypersensitivity were detected after pharmacological inhibition of Y1R. Remarkably, the activation of Y1R produced powerful analgesic effect: blocking both evoked and spontaneous pain behavior resulted from Y2R antagonism. These findings highlight the pivotal role of endogenous Y2R in gating mechanical and spontaneous pain transmission. Importantly, our results suggest that Y1R could be a therapeutic target that may be exploited for alleviating spontaneous pain without affecting acute pain transmission.

Original languageEnglish
JournalMolecular Pain
StatePublished - Jan 1 2019


  • NPY
  • Y1R
  • Y2R
  • pain
  • spinal cord

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