involvement of nitric oxide in clonidineinduced spinal analgesia background the chronic pain relieving effects following spinal administration of clonidine are probably connected to alpha2adrenoreceptorinduced augmented synthesis of nitric oxide no in the spinal cord in contrast when acute pain is considered the possible role of no is still speculative the aim of the present study was to explore the role of no in acute pain relief following intraspinal administration of clonidinemethods we used the mouse tailflick model of acute pain spinal injections of the following agents and their combinations were administered clonidine larginine no precursor the no production inhibitor nitrolargininemethyl ester lname the no antagonist methylene blue mb and nitroglycerine no releasing agentresults a 95 analgesic response was achieved with 20 microg clonidine larginine produced analgesia and larginine administration followed by clonidine resulted in a pronounced synergistic analgesic effect this synergistic effect was attenuated by lname pretreatment with mb decreased and nitroglycerine administration did not affect the clonidineinduced analgesiaconclusions no may be involved in the mediation of the acute pain relieving effects of intraspinally administered clonidine further research is warranted to establish the potential benefits and possibility for incorporation of no promoting agents in therapeutic regional pain regimens