title: Analgesic effects of cannabinoid receptor agonist WIN55,212-2 in the nucleus cuneiformis in animal models of acute and inflammatory pain in rats.
abstract: Nucleus cuneiformis (NCF) along with periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) is a part of descending system for pain modulation. Cannabinoids have analgesic effects on the PAG and RVM. This study investigates the possible role of cannabinoids in pain modulation in the NCF. Cannabinoid agonist, WIN55,212-2 (5, 10 and 20μg/0.3μl DMSO per side), and selective cannabinoid CB1 receptor antagonist, AM251(1, 5 and 10μg/0.3μl DMSO per side), were microinjected alone or in succession. As models of acute and inflammatory pain, tail-flick and formalin test were utilized to examine the effects of these drugs on pain modulation in 5min time blocks for 60min. Results of tail-flick and formalin tests demonstrated a dose-dependent analgesic effects for WIN55,212-2, with the most significant response at the dose of 20μg/side. The analgesic responses were more effective during the first 45-min period of the tail-flick test (P<0.001) and during the late phase (P<0.001) of formalin test, compared to the early phase (P<0.05). These analgesic effects were blocked in the presence of AM251 (1μg/0.3μl DMSO per side) in both tests. Administration of AM251 alone did not have any effect on nociceptive responses in either test. The cannabinoid-mediated analgesia demonstrated in this study suggests the presence of a cannabinoid-sensitive nociceptive modulatory system in the NCF.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ebrahimzadeh
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D048588:Benzoxazines / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000009:adverse effects; D006358:Hot Temperature / Q000009:adverse effects; D007249:Inflammation / Q000150:complications; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology*; D008845:Microinjections / Q000379:methods; D009025:Morpholines / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D013997:Time Factors
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D005557:Formaldehyde; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone