Wilder R T, Sholas M G, Berde C B
Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.
Anesth Analg. 1996 Dec;83(6):1251-5. doi: 10.1097/00000539-199612000-00021.
A model of local anesthetic tachyphylaxis was developed in our group previously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevented both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized that nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blocks were placed by percutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the first nerve block, rats received intraperitoneal injections with saline or one of six concentrations of NG-nitro-L-arginine methyl ester (L-NAME) in a randomized, blinded pattern. Control rats developed tachyphylaxis as seen previously: the duration of the third block was 30% that of the first. L-NAME inhibited the development of tachyphylaxis in a dose-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME at 0.2mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathways may be involved in the development of tachyphylaxis to local anesthetic nerve block.
我们小组之前通过在大鼠身上反复进行坐骨神经阻滞建立了局部麻醉快速耐受模型。在该模型中，热痛觉过敏加速了快速耐受，而非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801可预防痛觉过敏和快速耐受。一氧化氮被认为是脊髓中NMDA通路的第二信使，并且似乎参与痛觉过敏的脊髓机制。我们推测一氧化氮合酶抑制剂也会抑制快速耐受的发生。通过经皮注射2-氯普鲁卡因对大鼠进行反复坐骨神经阻滞。通过测量56℃热板潜伏期来测试阻滞持续时间。在第一次神经阻滞前两小时，大鼠以随机、盲法的方式接受腹腔注射生理盐水或六种浓度的NG-硝基-L-精氨酸甲酯（L-NAME）之一。对照大鼠如之前所见出现了快速耐受：第三次阻滞的持续时间为第一次的30%。L-NAME以剂量依赖的方式抑制快速耐受的发生；使用0.2mg/kg的L-NAME可使快速耐受抑制50%，而50mg/kg可完全消除快速耐受。一氧化氮通路可能参与局部麻醉神经阻滞快速耐受的发生。
