title: Involvement of the histaminergic system in the nociceptin-induced pain-related behaviors in the mouse spinal cord.
abstract: Intrathecal (i.t.) injection of nociceptin elicited a behavioral response mainly consisting of biting and licking, which were eliminated by the i.t. co-administration of opioid receptor-like-1 (ORL-1) receptor antagonists. The behavioral response induced by nociceptin was characteristically similar to that by i.t.-administered histamine, and was attenuated by i.t. co-administration of the H1 receptor antagonists, but not by the H2 receptor antagonists, whereas the H3 receptor antagonist promoted the nociceptin-induced behavior. H1 receptor knockout (H1R-KO) mice did not show the nociceptin-induced nociceptive behavior, which was observed in wild-type mice. Pretreatment with a histamine antiserum or a histidine decarboxylase inhibitor resulted in a significant reduction of the response to nociceptin. The previous studies showed that NK1 receptor antagonists and a novel substance P (SP)-specific antagonist given i.t. could reduce the behavioral response to nociceptin and histamine. On the other hand, the nociceptive response induced by nociceptin, but not histamine, was completely attenuated by the i.t. co-administration of agonists for GABAA and GABAB receptors. In contrast, the antagonists for GABAA and GABAB receptors injected i.t. showed same nociceptive response with nociceptin and histamine, and their nociceptive responses were significantly blocked by the i.t. co-administration of the H1 receptor antagonists, but not H2 receptor antagonists or ORL-1 receptor antagonists. The present results suggest that the activation of the ORL-1 receptor by nociceptin may induce the disinhibition of histaminergic neuron and enhance the release of histamine, which subsequently acts on the H1 receptor located on the SP-containing neurons to produce the spinal cord-mediated nociceptive response.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. s-sakura@tohoku-pharm.ac.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Orito
authors.forename: Sou
authors.initials: S
authors.lastname: Katsuyama
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Chikai
authors.initials: C
authors.lastname: Sakurada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000633:toxicity*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011968:Receptors, Histamine / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D006633:Histamine Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011968:Receptors, Histamine; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse