Persistent pain and stress activate pain-inhibitory orexin pathways

Shinji Watanabe, Tomoyuki Kuwaki, Masashi Yanagisawa, Yasuichiro Fukuda, Megumi Shimoyama

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


Orexins are synthesized by neurons in the hypothalamus and contribute to multiple physiological functions. Orexin fibers innervate many regions of the CNS, which include areas involved in descending control of pain. We examined the role orexins may play in endogenous modulation of pain transmission using prepro-orexin (precursor of orexin A and B) knockout mice. Baseline pain thresholds of knockout and wild type mice were not different. Knockout mice presented greater degree of hyperalgesia induced by peripheral inflammation and less stress-induced analgesia than wild type mice. Double staining of orexin and c-Fos in wild type mice revealed activation of orexin neurons under both conditions. These results suggest that persistent pain and stress activate orexin neurons, which act to inhibit pain transmission.

Original languageEnglish (US)
Pages (from-to)5-8
Number of pages4
Issue number1
StatePublished - Jan 19 2005


  • Hyperalgesia
  • Knockout mice
  • Orexin
  • Peripheral inflammation
  • Stress-induced analgesia

ASJC Scopus subject areas

  • Neuroscience(all)


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