In parallel to these initial results the sEHIs similarly reduce pain-related behavior in carrageenan induced inflammatory pain, even when administered hours after intraplantar carrageenan [57]. The efficacy of sEHIs on mechanical and thermal withdrawal behavior seems to vary between models and route of administration. Whereas in the LPS model the thermal latencies are greatly improved, in the carrageenan model the allodynia is more efficiently reduced by the sEH inhibitors. Nevertheless the anti-nociception produced by sEHIs is consistently independent of the administration route whether topical, subcutaneous, or intrathecal. Systemic and even topical administration of most sEHIs so far has resulted in high enough levels in the CNS to effectively inhibit sEH. Moreover, in the carrageenan model anti-nociceptive effects with direct spinal injections of very low doses of sEHIs suggest that at least a portion of the anti-nociceptive effects are centrally mediated [22]. In support of this hypothesis of central action we demonstrated that inhibition of sEH significantly suppressed the up-regulation of spinal COX-2 mRNA. This effect is of course expected from an anti-inflammatory agent that penetrates into the CNS and prevents
