title: Antinociceptive effect of cannabinoid agonist WIN 55,212-2 in rats with a spinal cord injury.
abstract: Spinal cord injury (SCI) pain exhibits many symptoms associated with peripheral neuropathic pain, including increased tactile hypersensitivity. One novel approach to ameliorate SCI pain is the use of cannabinoid (CB) ligands. The current study evaluated the efficacy of the nonselective CB receptor agonist WIN 55,212-2 on tactile hypersensitivity in rats following a brief compression to the thoracic spinal cord. The withdrawal thresholds of the hind paws following SCI were significantly decreased, indicating tactile hypersensitivity. Systemic injection of WIN 55,212-2 increased withdrawal thresholds in a dose-dependent manner. Pretreatment with the CB(1) receptor subtype-selective antagonist AM 251 completely abolished the antinociceptive effect of WIN 55,212-2 whereas pretreatment with the CB(2) receptor subtype-selective antagonist AM 630 did not alter the antinociceptive effect of WIN 55,212-2. These data indicate that a CB(1)-selective agonist may be novel therapeutic treatment for clinical SCI pain.
authors.affiliation: University of Miami Miller School of Medicine, The Miami Project to Cure Paralysis, 1095 NW 14th Terrace (R-48), Miami, FL 33136, USA. ahama@med.miami.edu
authors.forename: Aldric
authors.initials: A
authors.lastname: Hama
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sagen
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D006614:Hindlimb / Q000503:physiopathology; D006941:Hyperesthesia / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D017288:Pain Threshold; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D013117:Spinal Cord Compression / Q000150:complications; D013119:Spinal Cord Injuries / Q000150:complications*; D013904:Thoracic Vertebrae
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; 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