title: Sustained antinociceptive effect of cannabinoid receptor agonist WIN 55,212-2 over time in rat model of neuropathic spinal cord injury pain.
abstract: A significant complaint associated with spinal cord injury (SCI) is chronic pain, which includes symptoms such as cutaneous hypersensitivity and spontaneous unevoked pain and is difficult to treat with currently available drugs. One complication with current analgesics is tolerance, a decrease in efficacy with repeated treatment over time. One promising class of pharmacological treatment is cannabinoid (CB) receptor agonists. The current study assessed the efficacy of the CB receptor agonist WIN 55,212-2 (WIN) in a rat model of neuropathic SCI pain. Brief spinal compression leads to significant hindpaw hypersensitivity to tactile stimulation. WIN dose-dependently increased withdrawal thresholds and continued to demonstrate efficacy over a twice-daily 7-day treatment regimen. By contrast, the efficacy of morphine in SCI rats decreased over the same treatment period. Similarly, the antinociceptive efficacy of WIN to acute noxious heat in uninjured rats diminished over time. These data suggest that the sustained efficacy of a CB receptor agonist for pain could depend on the pain state. Such agonists may hold promise for long-term use in alleviating chronic SCI pain.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Leonard M. Miller School of Medicine, 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: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D048588:Benzoxazines / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009025:Morpholines / Q000627:therapeutic use*; D009281:Naphthalenes / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*
chemical_list: D000701:Analgesics, Opioid; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine