AM404, an inhibitor of anandamide reuptake decreases Fos-immunoreactivity in the spinal cord of neuropathic rats after non-noxious stimulation.
Cannabinoids like anandamide are involved in pain transmission. In this study we evaluated the effects of administrating N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404), an inhibitor of anandamide reuptake and monitoring the expression of c-fos, a marker of activated neurons in an experimental model of neuropathic pain (sciatic nerve tying). Fos expression was monitored 14 days after tying of sciatic nerve and 2 h after non-noxious stimulation. We showed that non-noxious stimulation increased Fos-positivity in the dorsal superficial laminae of the lumbar spinal cord of tied animals but not in the control animals. AM404 significantly reduced Fos induction in tied animals. Co-administration of cannabinoid CB1 receptor, cannabinoid CB2 receptor and transient receptor potential vanilloid type 1 (TRPV-1) antagonists reduced the effect of AM404 and this reduction was higher using cannabinoid CB1 receptor antagonist. These results suggest that AM404 could be a useful drug to reduce neuropathic pain and that cannabinoid CB1 receptor, cannabinoid CB2 receptor and vanilloid TRPV-1 receptor are involved.
Rodella
Luigi F
LF
Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, viale Europa 11, 25123 Brescia, Italy. rodella@med.unibs.it
Borsani
Elisa
E
Rezzani
Rita
R
Ricci
Francesca
F
Buffoli
Barbara
B
Bianchi
Rossella
R
D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; C103505:AM 251; C071423:capsazepine; D002211:Capsaicin; C094023:iodopravadoline; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide