Persistent pain and stress activate pain-inhibitory orexin pathways

Neuroreport. 2005 Jan 19;16(1):5-8. doi: 10.1097/00001756-200501190-00002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia
  • Animals
  • Carrageenan
  • Disease Models, Animal
  • Hypothalamus / physiology
  • Hypothalamus / physiopathology
  • Inflammation / physiopathology
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology
  • Neuropeptides / deficiency
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Neurotransmitter Agents
  • Orexins
  • Pain / physiopathology*
  • Stress, Physiological / physiopathology*


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • Orexins
  • Carrageenan