Abstract
Cannabinoids, such as anandamide, are involved in pain transmission. We evaluated the effects of AM404 ( N-(4-hydroxyphenyl)-5 Z,8 Z,11 Z,14 Z-eicosatetraenamide), an anandamide reuptake inhibitor, monitoring the expression of c- fos, a marker of activated neurons and the pain-related behaviours using formalin test. The study was carried out in an experimental model of inflammatory pain made by a single injection of formalin in rat hind paws. Formalin test showed that the antinociceptive effect of AM404 was evident in phase I. We found that Fos-positive neurons in dorsal superficial and deep laminae of the lumbar spinal cord increased in formalin-injected animals and that AM404 significantly reduced Fos induction. Co-administration of cannabinoid CB 1 receptor antagonist (AM251), cannabinoid CB 2 receptor antagonist (AM630) and transient receptor potential vanilloid type 1 (TRPV-1) antagonist (capsazepine), attenuate the inhibitory effect of AM404 and this effect was higher using cannabinoid CB 2 and vanilloid TRPV-1 receptor antagonists. These results suggest that AM404 could be a useful drug to reduce inflammatory pain in our experimental model and that cannabinoid CB 2 receptor and vanilloid TRPV-1 receptor, and to a lesser extent, the cannabinoid CB 1 receptor are involved.
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