中文摘要 |
全身性給予一氧化氮合成酵素(NOS )抑制劑L-Nw nitro-arginine methyl ester (L-NAME )包括了周邊消炎以及中樞神經的效果,因此必須從脊髓腔給予藥物才能排除NOS 抑制劑的周邊消炎作用,並進一步了解周邊刺激之後,脊髓內的被活化的NO 對於神經活動以及相關的疼痛行為的影響。先前研究發現L-NAME 脊髓注射不僅可以降低早期及晚期階段福馬林疼痛反應,亦呈現以劑量依賴的方式降低福馬林刺激後脊髓Fos 標記神經細胞的總量;而電針足三里穴亦能有效降低早、晚期福馬林疼痛反應,對於降低福馬林刺激後脊髓Fos 標記神經細胞總量的表現亦佳。然而傳統的針灸止痛與NOS 抑制劑L-NAME 結合在止痛的效果與阻斷疼痛訊息的傳遞上扮演怎樣的角色,是值得大家深入探討的課題。本研究隨機將30 隻Wistar 雄性鼠分為五組,分別在福馬林測試前30 分鐘經脊髓腔細管給予生理食鹽水、1000 nM L-NAME 及十倍強度電針、300 nM L-NAME 及十倍強度電針、1000nM L-NAME 及二十倍強度電針、300 nM L-NAME 及二十倍強度電針。以觀察疼痛行為反應與脊髓背角Fos 蛋白之數量來探討鎮痛效果與可能之機轉。研究結果顯示L-NAME 注射及電針刺激各組除了可以降低早期及晚期階段福馬林疼痛反應外,亦以相當劑量依賴性之趨勢對各層區(表淺層、中間層以及深層)的Fos 標記神經細胞產生抑制效果。而本研究證實了結合電針刺激與脊髓腔注射NOS 抑制劑對福馬林皮下注射有良好的止痛效果,就分子生物領域Fos 蛋白質的表現也取得全面的抑制效果,或可作為醫師臨床上對付各種頑固性疼痛治療的參考。Systematically administrated nitric oxide synthase (NOS) inhibitor, L-Nω nitro-arginine methyl ester (L-NAME), does-dependently reduced c-fos expression in the rat lumbar spinal cord. The effects of treatment of NOS inhibitors include anti-inflammation in peripheral system and analgesia in central system. Dosage by intrathecal could exclude the anti-inflammation effect of NOS inhibitors. To investigate the effects of activated NOS in spinal cord on neuronal activities and related behaviors of pain following peripheral stimulation, we examined formalin-induced hyperalgesia and c-fos expression following treatment of NOS inhibitor (L-NAME) by the route of spinal cord combined with electroacupuncture on Zusanli in order to seek the best analgesia strategy. We observed that L-NAME (300, 1000 nM) administrated intratecally combined with (10 X, 20 X) intensity of electroacupuncture on Zusanli decreased both primary and late stage of hyperalgesia effects induced by formalin (p < 0.01); And these treatments decreased the amount of cfos- labeled neurons in all three regions of dorsal horn (the superficial lamina, nucleus propius and deep lamina) in a likely dose dependent manner. Electroacupuncture combined with L-NAME treatments maybe the best choice of the analgesia strategy in the clinics. |