The CB2 receptor agonists mediate analgesia without CNS side effects observed for CB1 agonists [75]. EFAs share structural similarities with agonists of CB receptors that induce anti-nociception. In addition the activity profiles of sEHI administration and EFAs have several similarities with CB2 agonists. Inhibitors of sEH do not have activity in the absence of pain, they are not motor impairing and they do not affect open field activity. They are both effective in inflammatory and neuropathic pain models. Cannabinoid and EFA anti-nociceptive systems both have cAMP mediated mechanisms. Synthesis of the endocannabinoid precursor N-acylphosphatidylethanolamine (NAPE) is driven by cAMP in neurons [76] and there is evidence of cAMP synergizing sEHI anti-nociception [60]. Overall there seems to be a great deal of similarity in the ways that EFAs and endocannabinoids affect the nociceptive system.
