내 • 외인성으로 유도된 Nitric Oxide 가 흰쥐의 통각전달에 미치는 효과

초록

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300ug/paw), sidium nitroprusside (600ug/paw), and L-arginine (300ug/paw) represented antinociceptive effect to noxious topical stimulus, but ptonociceptive responses followed by spinally application (20ug/5ul,10ug/3ul/500ug/5ul respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300ug/paw) and NOS inhibitor (20mg/kg, L-NAME of L-NOArg) are injectde into right hind paw (I.pl.).When verapamil is combined with NOS inhibitor, analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rat`s hind paw (0.05ml), elicited a biphasic responses and nitric oxide had an analgesic effect on both Adelta and C sensory nerve fivers which manipulate the phases repectively. Nitric oxides, which produced form consitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX1 enzyme, when pretreated intraperitoneally (100mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressde hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

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