n-arachidonylglycine and Inflammation

This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Disease Models, Animal; Dronabinol; Drug Evaluation, Preclinical; Eicosanoids; Endocannabinoids; Fibromyalgia; Glycine; Humans; Inflammation; Mice; Plant Oils; Randomized Controlled Trials as Topic; Rats; Receptors, Cannabinoid

While cannabinoid receptor agonists have analgesic activity in inflammatory pain states they produce a range of side effects. Recently, it has been demonstrated that the arachidonic acid-amino acid conjugate, N-arachidonyl-glycine (NA-glycine) is effective in acute pain models.. In the present study we examined the effect of NA-glycine in a rat model of inflammatory pain. Intrathecal administration of NA-glycine (70 - 700 nmol) and the pan-cannabinoid receptor agonist HU-210 (10 nmol) reduced the mechanical allodynia and thermal hyperalgesia induced by intraplantar injection of Freund's complete adjuvant (FCA). The actions of HU-210, but not NA-glycine were reduced by the cannabinoid CB1 receptor antagonist AM251. The cannabinoid CB2 receptor antagonist SR144528 also had no effect on the actions of NA-glycine. In contrast, N-arachidonyl-GABA (NA-GABA, 700 nmol) and N-arachidonyl-alanine (NA-alanine, 700 nmol) had no effect on allodynia and hyperalgesia. HU-210, but not NA-glycine produced a reduction in rotarod latency.. These findings suggest that NA-glycine may provide a novel non-cannabinoid receptor mediated approach to alleviate inflammatory pain.

Topics: Animals; Arachidonic Acids; Cannabinoid Receptor Agonists; Disease Models, Animal; Glycine; Inflammation; Injections, Spinal; Male; Pain; Rats; Rats, Sprague-Dawley; Reaction Time