title: Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice.
abstract: Orexins are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus, and related to the central control of appetite, arousal, and antinociception. Orexin neurons projected to the tuberomammillary nucleus and orexins may release histamine from the histamine neurons in this nucleus. Histamine is known to cause hypernociception. The roles of histamine H1 and H2 receptors in the orexin A-induced antinociception, however, have not been clarified yet. Here we studied the effects of histamine H1 and H2 receptors on orexin A-produced antinociception using histamine receptor knockout mice in four assays of nociception; the hot-plate, the tail-flick, the tail-pressure and the capsaicin tests. Furthermore we studied effects of histamine H1 and H2 receptor antagonists on orexin A-produced antinociception in C57BL/6 mice. The antinociceptive effects of i.c.v. orexin A were greater in histamine H1 receptor or H2 receptor knockout mice than in the wild-type mice in all four assays of pain. Furthermore, treatment of C57BL/6 mice with a combination of i.c.v. orexin A and d-chlorpheniramine (a histamine H1 receptor antagonist) or cimetidine (a histamine H2 receptor antagonist) showed a greater antinociception than i.c.v. orexin A alone in all four assays. These findings suggest the possibility that orexin A may activate H1 and H2 receptors in the supraspinal levels through the release of histamine from neurons, which might attenuate the antinociceptive effects of orexin A. Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception.
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan. jalalizadi2002@yahoo.com
authors.forename: Jalal Izadi
authors.initials: JI
authors.lastname: Mobarakeh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Motohisa
authors.initials: M
authors.lastname: Kato
authors.forename: Nasser
authors.initials: N
authors.lastname: Naghdi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D018013:Receptors, Neuropeptide
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018013:Receptors, Neuropeptide; D002744:Chlorpheniramine