Jones D L, Sorkin L S
Department of Anesthesiology, University of California San Diego, Anesthesia Research Labs-0818, 9500 Gilman Drive, La Jolla, CA 92093-0818, USA.
Brain Res. 1998 Nov 9;810(1-2):93-9. doi: 10.1016/s0006-8993(98)00890-7.
Gabapentin (GBP) and S(+)-3-isobutyl-gamma-aminobutyric acid (IBG) are anticonvulsant agents which are effective against many clinical and experimental neuropathic pain states. We examined the efficacy of these agents in a new rat model of secondary mechanical hyperalgesia generated by a mild thermal injury. Under brief halothane anesthesia, an injury was induced by applying one heel to a hot surface (52.5 degreesC) for 45 s. GBP, IBG or saline was injected i.p. just prior to the injury. Mean mechanical withdrawal threshold (MWT) was determined using von Frey hairs before and at 30 min intervals for 3 h following the injury. MWT outside the injury area decreased post-injury (secondary hyperalgesia, allodynia), but primary (site of injury) mechanical hyperalgesia was not observed. Secondary hyperalgesia exhibited a tendency toward recovery over time. Time to onset of the anti-allodynic effect of GBP was 30-60 min. The minimum effective GBP dose was 100 mg/kg; 300 mg/kg GBP totally inhibited the drop in MWT, but was accompanied by pronounced sedation. Anti-allodynic effects of IBG were apparent at the first post-injury measure of MWT (30 min). Thirty milligrams per kilogram was the minimum effective dose; 100 mg/kg IBG totally blocked the allodynia with minimal side effects. Our findings demonstrate a dose-dependent blockade of the mechanical sensitivity caused by a mild thermal injury by both GBP and IBG. Results indicate that IBG is more effective than GBP in this model at doses which do not cause sedation. These observations support the suggested use of these or related gamma-amino acid analogues as an effective treatment for post-operative pain.
加巴喷丁（GBP）和S（+）-3-异丁基-γ-氨基丁酸（IBG）是抗惊厥药物，对许多临床和实验性神经性疼痛状态有效。我们在一种由轻度热损伤产生的继发性机械性痛觉过敏的新大鼠模型中研究了这些药物的疗效。在短暂的氟烷麻醉下，将一只足跟置于热表面（52.5℃）45秒以诱导损伤。在损伤前经腹腔注射GBP、IBG或生理盐水。在损伤前及损伤后3小时内每隔30分钟使用von Frey毛发测定平均机械性撤针阈值（MWT）。损伤区域外的MWT在损伤后降低（继发性痛觉过敏、异常性疼痛），但未观察到原发性（损伤部位）机械性痛觉过敏。继发性痛觉过敏随时间有恢复趋势。GBP抗异常性疼痛作用的起效时间为30 - 60分钟。GBP的最小有效剂量为100mg/kg；300mg/kg GBP完全抑制MWT下降，但伴有明显的镇静作用。IBG的抗异常性疼痛作用在损伤后首次MWT测量时（30分钟）就很明显。30mg/kg是最小有效剂量；100mg/kg IBG完全阻断异常性疼痛且副作用最小。我们的研究结果表明，GBP和IBG对轻度热损伤引起的机械性敏感性均有剂量依赖性阻断作用。结果表明，在该模型中，在不引起镇静的剂量下，IBG比GBP更有效。这些观察结果支持将这些或相关的γ-氨基酸类似物用作术后疼痛的有效治疗方法。
