Actions of N-arachidonyl-glycine in a rat neuropathic pain model.
While cannabinoid receptor agonists reduce the abnormal pain sensations associated with animal models of neuropathic pain states they also produce CB(1) receptor mediated side effects. Recently, a number of arachidonic acid-amino acid conjugates, including N-arachidonyl-glycine (NAGly), have been identified which are structurally related to the endocannabinoid arachidonyl ethanolamide (anandamide). In the present study we examined the effect of NAGly in a rat model of neuropathic pain. Intrathecal administration of NAGly (700 nmol) and the pan-cannabinoid receptor agonist HU-210 (30 nmol) reduced the mechanical allodynia induced by partial ligation of the sciatic nerve. The NAGly induced anti-allodynia was dose dependent and, unlike HU-210, was unaffected by the cannabinoid CB(1) and CB(2) receptor antagonists, AM251 and SR144528 (30 nmol). The NAGly degradation products, arachidonic acid and glycine (700 nmol), did not reduce allodynia. HU-210, but not NAGly produced a reduction in rotarod latency. These findings suggest that NAGly may provide a novel analgesic approach to alleviate neuropathic pain.
Vuong
Leeza A Q
LA
Pain Management Research Institute, Kolling Institute, Northern Clinical School, The University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
Mitchell
Vanessa A
VA
Vaughan
Christopher W
CW
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use*; D019540:Area Under Curve; D001892:Camphanes / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D010147:Pain Measurement / Q000379:methods; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000188:drug therapy* / Q000503:physiopathology
D000700:Analgesics; D001095:Arachidonic Acids; D001892:Camphanes; C465623:N-arachidonylglycine; D010880:Piperidines; D011720:Pyrazoles; C110630:SR 144528; C103505:AM 251; D013759:Dronabinol; C062018:HU 211; D005998:Glycine