title: Lateral Hypothalamic Stimulation Reduces Hyperalgesia Through Spinally Descending Orexin-A Neurons in Neuropathic Pain.
abstract: No evidence to date shows that lateral hypothalamic (LH) stimulation produces orexin-A-mediated antinociception in the spinal cord dorsal horn (SCDH) in a model of neuropathic pain. We conducted experiments to examine the effect of orexin-A-mediated LH stimulation in female rats with chronic constriction injury (CCI) on thermal hyperalgesia. Rats receiving carbachol into the LH demonstrated antinociception on both the left CCI and right nonligated paws (p < .05). Rats were given carbachol in the LH followed by intrathecal injection of the orexin-1 (OX1) receptor antagonist SB-334867, which blocked LH-induced antinociception compared with control groups (p < .05) in the left paw, but not in the right paw. These findings support the hypothesis that LH stimulation produces antinociception in rats with thermal hyperalgesia from neuropathic pain via an orexin-A connection between the LH and the SCDH. Identification of this pathway may lead to studies using orexins to manage clinical pain.
authors.affiliation: University of Michigan, Ann Arbor, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Wardach
authors.affiliation: University of Michigan, Ann Arbor, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Kyung Hee University, Seoul, South Korea.
authors.forename: Younhee
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: University of Michigan, Ann Arbor, USA holdenje@umich.edu.
authors.forename: Janean E
authors.initials: JE
authors.lastname: Holden
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy*; D007026:Hypothalamic Area, Lateral / Q000503:physiopathology*; D009287:Naphthyridines; D009437:Neuralgia / Q000188:drug therapy*; D000068797:Orexins / Q000037:antagonists & inhibitors*; D059408:Pain Management; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000503:physiopathology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D018712:Analgesics, Non-Narcotic; D001583:Benzoxazoles; D009287:Naphthyridines; D000068797:Orexins; D014508:Urea; D002217:Carbachol
keywords: lateral hypothalamus; neuropathic pain; orexin