Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy

Background: influence of a relatively specific inhibitor cyclooxygenase (cox)-2,celecoxib,a relatively specific inhibitor of neuronal nitric oxide synthase (nos),7-ni,and a relatively selective inhibitor of inducible nos,l-nil,on the action of a preferentially selective cb1 cannabinoid receptor agonist,met-f-aea and a selective cb2 cannabinoid receptor agonist,am 1241 was investigated,in a streptozotocin (stz)-induced neuropathy. methods: studies were performed on male wistar rats. changes in nociceptive thresholds were determined using mechanical stimuli - the modification of the classic paw withdrawal test described by randall-selitto. diabetes was induced by a single administration of stz. results: in a diabetic neuropathic pain model,pretreatment with celecoxib,l-nil and 7-ni,significantly increased the antihyperalgesic activity of both met-f-aea and am 1241. conclusions: the results of this study seemed to indicate that the interaction between cannabinoid,cox-2 and nos(s) systems might exist. concomitant administration of small doses of cb1 and/or cb2 receptor agonists and cox-2 or nos inhibitors can be effective in the alleviation of diabetic neuropathic pain. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban & partner sp. z o.o. all rights reserved.