using a pain model involving direct intraplantar administration of PGE2 [60]. Given that PGE2 is a product of both COX isozymes, the non-selective inhibitor indomethacin displays no efficacy on this type of pain [61].Consistent with these earlier findings celecoxib and dexamethasone both of which are strongly anti-inflammatory do not affect allodynia elicited by intraplantar PGE2 [60]. Surprisingly structurally different sEHIs do block pain produced by PGE2 differentiating sEHIs from NSAIDs, selective COX inhibitors and steroids as a separate class of analgesic agents. Thus EFAs do not modulate transmission of nociceptive information under physiological conditions but their effects are switched on under pathophysiological conditions whether the pathology is inflammatory or neuropathic. Such observations indicate that EFAs influence a more fundamental aspect of pain transmission. The sEHIs are also different from narcotic agents which elevate acute pain thresholds of naïve rodents. Overall the sEHIs have a distinct profile of anti-nociceptive effects from known agents that reduce pain suggesting that they may be useful in the treatment of pain.
