Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test

• Published in: Pharmacology, biochemistry and behavior Vol. 112; pp. 64 - 70
• Main Authors: Azhdari-Zarmehri, Hassan, Esmaeili, Mohammad-Hossein, Sofiabadi, Mohammad, Haghdoost-Yazdi, Hashem
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Analgesics - antagonists & inhibitors; Analgesics - pharmacology; Animals; Benzoxazoles - pharmacology; Formalin test; Injections, Intraventricular; Morphine; Morphine - antagonists & inhibitors; Morphine - pharmacology; Orexin Receptor Antagonists; Orexin receptor type-1; Pain Measurement; Rat; Rats; Receptors, Neuropeptide - antagonists & inhibitors; Urea - analogs & derivatives; Urea - pharmacology; Morphine; Orexin receptor type-1; Rat; Formalin test
• ISSN: 0091-3057; 1873-5177; 1873-5177
• DOI: 10.1016/j.pbb.2013.09.018

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 0.5nmol 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 5nmol considerably attenuated the morphine-induced analgesia (at dose 1.5mg/kg of morphine; phase 1, interphase, and phase 2, at dose 3 and 6mg/kg of morphine just phase 2 of formalin test). Pre-treatment with SB-334867 at a dose of 50nmol 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 6mg/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. •Morphine injection decreased the formalin induced nociceptive behaviors.•ICV injection of SB-334867 alone had no effect on formalin test.•Pre-treatment with SB-334867 attenuated the morphine-induced analgesia.