Jun J H, Yaksh T L
Department of Anesthesiology, Hanyang University College of Medicine, Seoul, Korea.
Anesth Analg. 1998 Feb;86(2):348-54. doi: 10.1097/00000539-199802000-00025.
Gabapentin is an anticonvulsant that may represent a novel class of drugs, which has novel spinal antihyperalgesic activity. We sought to characterize this spinal action in a model of hyperalgesia that involves a mild thermal injury to the hind paw of the rat. Rats were prepared with chronic spinal catheters. Under brief halothane anesthesia, a thermal injury was induced by applying the left hind paw to a thermal surface (52.5 degrees C) for 45 s. This exposure results in mild erythema but no blistering. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus with which response latencies of the injured and uninjured (normal) paw could be obtained. Thirty minutes after thermal injury, the response latency in all groups decreased from 10-12 s to 5-7 s. Uninjured paw withdrawal latency was unaltered. The intrathecal injection of gabapentin (30-300 microg) produced a dose-dependent reversal of the hyperalgesia but had no effect on the response latency of the normal hind paw, even at the largest doses. A similar reversal was observed after intrathecal delivery of the structural analog S(+)-3-isobutyl gamma-aminobutyric acid (GABA) (30-300 microg), but not after the largest dose of its stereoisomer R(-)-3-isobutyl GABA (300 microg). The effects of both intrathecal gabapentin and S(+)-3-isobutyl GABA were reversed by intrathecal D-serine, but not L-serine. All effects were observed at doses that had no significant effect on motor function. These observations, in conjunction with the accumulating data on binding and transmitter release, emphasize that these gabapentinoids can selectively modulate the facilitation of spinal nociceptive processing otherwise generated by persistent small afferent input generated by tissue injury.
Gabapentin and its analog, 3-isobutyl gamma-aminobutyric acid, given spinally, produce a dose-dependent, D-serine-sensitive reversal of the thermal hyperalgesia evoked by mild thermal injury.
加巴喷丁是一种抗惊厥药，可能代表一类新型药物，具有新型的脊髓抗痛觉过敏活性。我们试图在一种痛觉过敏模型中表征这种脊髓作用，该模型涉及对大鼠后爪的轻度热损伤。给大鼠植入慢性脊髓导管。在短暂的氟烷麻醉下，将左后爪置于热表面（52.5摄氏度）45秒以诱导热损伤。这种暴露导致轻度红斑但无水泡形成。使用玻璃下热刺激测定后爪的热逃避潜伏期，通过该刺激可获得受伤爪和未受伤（正常）爪的反应潜伏期。热损伤30分钟后，所有组的反应潜伏期从10 - 12秒降至5 - 7秒。未受伤爪的撤离潜伏期未改变。鞘内注射加巴喷丁（30 - 300微克）产生剂量依赖性的痛觉过敏逆转，但即使在最大剂量下，对正常后爪的反应潜伏期也没有影响。鞘内注射结构类似物S(+)-3-异丁基γ-氨基丁酸（GABA）（30 - 300微克）后观察到类似的逆转，但在最大剂量的其立体异构体R(-)-3-异丁基GABA（300微克）注射后未观察到。鞘内注射D-丝氨酸可逆转鞘内加巴喷丁和S(+)-3-异丁基GABA的作用，但L-丝氨酸不能。所有作用均在对运动功能无显著影响的剂量下观察到。这些观察结果，结合关于结合和递质释放的越来越多的数据，强调这些加巴喷丁类药物可以选择性地调节脊髓伤害性处理的易化，否则这种易化是由组织损伤产生的持续性小传入输入所引起的。
鞘内给予加巴喷丁及其类似物3-异丁基γ-氨基丁酸可产生剂量依赖性的、对D-丝氨酸敏感的对轻度热损伤诱发的热痛觉过敏的逆转。
