Lee K C, Wilder R T, Smith R L, Berde C B
Department of Anesthesia, Children's Hospital, Boston, Massachusetts 02115.
Anesthesiology. 1994 Nov;81(5):1284-93. doi: 10.1097/00000542-199411000-00024.
Tachyphylaxis to local anesthetics has been shown to be promoted by longer interanalgesic intervals between injections. We hypothesized that thermal hyperalgesia also would accelerate the development of tachyphylaxis. The n-methyl-D-aspartate antagonist ((+)-5 methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine, or dizocilpine) (MK-801) has been shown to prevent thermal hyperalgesia. We therefore also hypothesized that MK-801 would prevent tachyphylaxis.
Catheters were surgically implanted in rats along the sciatic nerve. After recovery and conditioning to the testing paradigm, they received repeated injections of lidocaine or 2-chloroprocaine followed by motor block testing with or without hot-plate testing at 48, 52, or 56 degrees C. In other experiments, MK-801 or saline was administered by intraperitoneal injection before sciatic nerve local anesthetic injection and sensory and motor testing.
Rats receiving repeated lidocaine or 2-chloroprocaine injections, when repeatedly subjected to hot-plate testing at 56 degrees C, developed thermal hyperalgesia and tachyphylaxis to motor and sensory blockade. Rats receiving either no hot-plate exposure or hot-plate exposure at 48 degrees C developed no tachyphylaxis or hyperalgesia. Rats tested at 52 degrees C developed milder hyperalgesia and developed tachyphylaxis more slowly than did rats tested at 56 degrees C. Control experiments excluded artifacts due to circadian rhythm, injection volume, and learning. Rats pretreated with MK-801 showed no tachyphylaxis over a series of three injections.
Thermal hyperalgesia accelerates the development of tachyphylaxis to rat sciatic nerve blockade, and MK-801 prevents tachyphylaxis in this model. n-Methyl-D-aspartate receptor antagonists may have future clinical utility in increasing the duration of effectiveness of prolonged local anesthetic administration.
研究表明，注射之间较长的镇痛间隔会促进对局部麻醉药的快速耐受性。我们推测热痛觉过敏也会加速快速耐受性的发展。N-甲基-D-天冬氨酸拮抗剂（（+）-5-甲基-10,11-二氢-5H-二苯并（a,d）环庚烯-5,10-亚胺，或地佐环平）（MK-801）已被证明可预防热痛觉过敏。因此，我们还推测MK-801可预防快速耐受性。
通过手术将导管植入大鼠坐骨神经沿线。恢复并适应测试范式后，给它们重复注射利多卡因或2-氯普鲁卡因，然后在48、52或56摄氏度下进行运动阻滞测试，同时进行或不进行热板测试。在其他实验中，在坐骨神经局部麻醉注射以及感觉和运动测试之前，通过腹腔注射给予MK-801或生理盐水。
接受重复利多卡因或2-氯普鲁卡因注射的大鼠，当在56摄氏度下反复进行热板测试时，会出现热痛觉过敏以及对运动和感觉阻滞的快速耐受性。未接受热板暴露或在48摄氏度下接受热板暴露的大鼠未出现快速耐受性或痛觉过敏。在52摄氏度下测试的大鼠出现的痛觉过敏较轻，且与在56摄氏度下测试的大鼠相比，快速耐受性发展较慢。对照实验排除了昼夜节律、注射量和学习导致的假象。用MK-801预处理的大鼠在一系列三次注射中未出现快速耐受性。
热痛觉过敏加速了大鼠坐骨神经阻滞快速耐受性的发展，且MK-801可预防该模型中的快速耐受性。N-甲基-D-天冬氨酸受体拮抗剂在延长局部麻醉药给药的有效持续时间方面可能具有未来临床应用价值。
