Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models.
1. Although cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central cannabinoid CB(1) receptor-mediated motor and psychotropic side-effects. The actions of endocannabinoids, such as anandamide, are terminated by uptake and subsequent intracellular enzymatic degradation. In the present study, we examined the effect of acute administration of the anandamide transport inhibitor AM404 in rat models of chronic neuropathic and inflammatory pain. 2. Systemic administration of AM404 (10 mg/kg) reduced mechanical allodynia in the partial sciatic nerve ligation (PNL) model of neuropathic pain, but not in the complete Freund's adjuvant (CFA) model of inflammatory pain. 3. The effect of AM404 in the PNL model was abolished by coapplication with the selective cannabinoid CB(1) receptor antagonist AM251 (1 mg/kg). AM404 did not produce a reduction in motor performance in either the PNL or CFA models. 4. These findings suggest that acute administration of AM404 reduces allodynia in a neuropathic pain model via cannabinoid CB(1) receptor activation, without causing the undesirable motor disruption associated with cannabinoid receptor agonists.
Mitchell
Vanessa A
VA
Pain Management Research Institute, Kolling Institute, Northern Clinical School, The University of Sydney, St Leonards, New South Wales, Australia.
Greenwood
Ruth
R
Jayamanne
Angelo
A
Vaughan
Christopher W
CW
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008026:Ligation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000601:surgery; D020426:Sciatic Neuropathy / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors
D000700:Analgesics; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002352:Carrier Proteins; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D005620:Freund's Adjuvant; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide