title: Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain.
abstract: Activation of CNS cannabinoid subtype-1 (CB1) receptors has been shown to mediate the antinociceptive and other effects of systemically administered CB receptor agonists. The endogenous peptide CB receptor ligand hemopressin (HE) has previously demonstrated an antinociceptive effect in rats with a hind paw inflammation, without exhibiting characteristic CB1 receptor-mediated side-effects. The current study evaluated the effect of intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of HE in a rat model of neuropathic spinal cord injury (SCI) pain. The non-subtype selective CB receptor agonist WIN 55,212-2 was also centrally administered in SCI rats as a comparator. Four weeks following an acute compression of the mid-thoracic spinal cord, rats displayed markedly decreased hind paw withdrawal thresholds, indicative of below-level neuropathic pain. Central administration of WIN 55,212-2 significantly increased withdrawal thresholds, whereas HE did not. Hemopressin has been reported to block CB1 receptors in vitro, similar to the CB1 receptor antagonist rimonabant. Pretreatment with rimonabant completely blocked the antinociceptive effect of centrally administered WIN 55,212-2, but pretreatment with HE did not. While the data confirm that activation of either supraspinal or spinal CB1 receptors leads to significant antinociception in SCI rats, the current data do not support an antinociceptive effect from an acute blockade of central CB1 receptors, HE's putative antinociceptive mechanism, in neuropathic SCI rats. Although such a mechanism could be useful in other models of pain with a significant inflammatory component, the current data indicate that activation of CB1 receptors is needed to ameliorate neuropathic SCI pain.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. hama2000_99@yahoo.com
authors.forename: Aldric
authors.initials: A
authors.lastname: Hama
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sagen
mesh_terms: D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D006454:Hemoglobins; D009025:Morpholines; D009281:Naphthalenes; D010446:Peptide Fragments; D043884:Receptor, Cannabinoid, CB1; C473218:hemopressin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone