AM404, an inhibitor of anandamide reuptake decreases Fos-immunoreactivity in the spinal cord of neuropathic rats after non-noxious stimulation.

Abstract	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.
Authors	Luigi F Rodella, Elisa Borsani, Rita Rezzani, Francesca Ricci, Barbara Buffoli, Rossella Bianchi
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 508 Issue 1-3 Pg. 139-46 (Jan 31 2005) ISSN: 0014-2999 [Print] Netherlands
PMID	15680264 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Arachidonic Acids Endocannabinoids Indoles Piperidines Polyunsaturated Alkamides Proto-Oncogene Proteins c-fos Pyrazoles AM 251 capsazepine Capsaicin iodopravadoline anandamide N-(4-hydroxyphenyl)arachidonylamide
Topics	Animals Arachidonic Acids (antagonists & inhibitors, metabolism, pharmacology) Capsaicin (analogs & derivatives, pharmacology) Constriction Dose-Response Relationship, Drug Endocannabinoids Immunohistochemistry Indoles (pharmacology) Male Physical Stimulation Piperidines (pharmacology) Polyunsaturated Alkamides Proto-Oncogene Proteins c-fos (analysis) Pyrazoles (pharmacology) Rats Rats, Sprague-Dawley Sciatic Nerve (injuries, physiopathology) Spinal Cord (drug effects, metabolism)

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