title: Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test.
abstract: Orexin-A and orexin-B are two neuropeptides selectively synthesized in the lateral hypothalamus (LH), a region involved in morphine induced analgesia and pain modulation. Furthermore, orexin-A has been reported to produce an analgesic effect in pain models, which was blocked by orexin-1 receptor antagonist SB-334867, but not naloxone. We studied the effects of intracerebroventricular (ICV) injection of SB-334867, a selective orexin receptor type-1 antagonist, on morphine-induced antinociceptive effect in formalin test in rats. Morphine injection at a dose of 1.5mg/kg caused a significant decrease in the formalin-induced nociceptive behaviors in phase 1, interphase, and phase 2A, whereas at doses of 3, 6, and 10mg/kg, a significant reduction in the formalin-induced nociceptive behaviors was observed in all phases. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment with SB-334867 at a dose of 0.5 nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test). Also, pre-treatment with SB-334867 at a dose of 5 nmol considerably attenuated the morphine-induced analgesia (at dose 1.5mg/kg of morphine; phase 1, interphase, and phase 2, at dose 3 and 6 mg/kg of morphine just phase 2 of formalin test). Pre-treatment with SB-334867 at a dose of 50 nmol remarkably attenuated the morphine-induced analgesia (at dose 1.5 and 3mg/kg of morphine; in phase 1, interphase, and phase 2 and also at dose 6 mg/kg of morphine; phase 1 and phase 2B of formalin test). These data suggest that the antinociceptive effects of morphine in formalin test might be associated with orexin receptor type-1. Our findings reveal a new role for the lateral hypothalamus orexin neurons in the morphine-induced analgesia.
authors.affiliation: Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran; Department of Physiology, Qazvin University of Medical Science, Qazvin, Iran. Electronic address: hasan.azhdari@gmail.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Azhdari-Zarmehri
authors.forename: Mohammad-Hossein
authors.initials: MH
authors.lastname: Esmaeili
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sofiabadi
authors.forename: Hashem
authors.initials: H
authors.lastname: Haghdoost-Yazdi
mesh_terms: D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D010147:Pain Measurement; D051381:Rats; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D000700:Analgesics; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D018013:Receptors, Neuropeptide; D009020:Morphine; D014508:Urea
keywords: Formalin test; Morphine; Orexin receptor type-1; Rat