title: Anti-allodynic and anti-hyperalgesic effects of nociceptin receptor antagonist, JTC-801, in rats after spinal nerve injury and inflammation.
abstract: The effects of nociceptin/orphanin FQ (N/OFQ) peptide receptor antagonist JTC-801 on allodynia and hyperalgesia were examined in rats in order to explore the involvement of N/OFQ system in these pathological pain states. Tactile allodynia induced by L5/L6 spinal nerve ligation was reversed by both systemic (3-30 mg/kg) and spinal (22.5 and 45 pg) JTC-801 in a dose-dependent manner. Concerning hyperalgesia induced by formalin injection into the hindpaw, JTC-801 dose-dependently suppressed the second phase, but not the first phase, of the licking behavior. Furthermore, systemic JTC-801 reduced Fos-like immunoreactivity in the dorsal horn of the spinal cord (laminae I/II). In conclusion, N/OFQ receptor antagonist JTC-801 exerted anti-allodynic and anti-hyperalgesic effects in rats, suggesting that N/OFQ system might be involved in the modulation of neuropathic pain and inflammatory hyperalgesia.
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. tamaih-dis@h.u-tokyo.ac.jp
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Tamai
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sawamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeda
authors.forename: Ryo
authors.initials: R
authors.lastname: Orii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control*; D006941:Hyperesthesia / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009292:Narcotic Antagonists; D009443:Neuritis / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D014110:Touch; D000094942:Nociceptin Receptor
chemical_list: D000634:Aminoquinolines; D001549:Benzamides; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C433236:N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide; C000722285:Oprl1 protein, rat