Nozaki-Taguchi N, Yamamoto T
Department of Anesthesiology, School of Medicine, Chiba University, Japan.
Anesth Analg. 1998 Feb;86(2):367-73. doi: 10.1097/00000539-199802000-00028.
Nitric oxide (NO) may play an important role in central and peripheral nociceptive processes. However, its contribution to peripheral antinociception is still not clear. In the present study, we investigated the effect of peripherally administered FK409, a spontaneous NO releaser, and its interaction with peripheral morphine analgesia during the rat formalin test. Intraplantar injection of formalin resulted in a biphasic appearance of flinching behavior (Phase 1 = 0-9 min, Phase 2 = 10-60 min). First, an intraplantar injection of FK409 was given 5 min before the formalin injection to test for its effect alone. In the next experiment, morphine was administered first, followed 15 min later by the phosphate buffer (pH 6.0) or FK409 injection, and 5 min later by the formalin injection. FK409 alone had no effect on the number of flinches in either phase. However, when administered after intraplantar morphine, FK409 dose-dependently depressed the agitation behavior in both phases. It shifted the dose-response curve of morphine to the left. Naloxone and carboxy-PTIO (an NO scavenger) each reversed the suppressant effect of morphine and FK409 given together. These data suggest that NO enhances the analgesic effect of peripherally administered morphine in the formalin test.
Peripherally administered nitric oxide itself has no analgesic effect, but it enhances the analgesic effects of peripherally administered morphine during inflammation induced by paw formalin injection in the rat.
一氧化氮（NO）可能在中枢和外周伤害感受过程中发挥重要作用。然而，其对外周抗伤害感受的贡献仍不清楚。在本研究中，我们在大鼠福尔马林试验期间研究了外周给予的FK409（一种自发释放NO的物质）的作用及其与外周吗啡镇痛的相互作用。足底注射福尔马林导致退缩行为呈双相出现（第1阶段=0 - 9分钟，第2阶段=10 - 60分钟）。首先，在福尔马林注射前5分钟进行足底注射FK409以测试其单独作用。在接下来的实验中，先给予吗啡，15分钟后注射磷酸盐缓冲液（pH 6.0）或FK409，5分钟后注射福尔马林。单独使用FK409对两个阶段的退缩次数均无影响。然而，在足底注射吗啡后给予FK409时，FK409剂量依赖性地抑制了两个阶段的激动行为。它将吗啡的剂量 - 反应曲线向左移动。纳洛酮和羧基 - PTIO（一种NO清除剂）各自逆转了吗啡和FK409联合给药的抑制作用。这些数据表明，在福尔马林试验中，NO增强了外周给予吗啡的镇痛作用。
外周给予的一氧化氮本身没有镇痛作用，但在大鼠爪部福尔马林注射诱导的炎症过程中，它增强了外周给予吗啡的镇痛作用。
