Chronic intrathecal infusion of gabapentin prevents nerve ligation-induced pain in rats
Chronic intrathecal infusion of gabapentin prevents nerve ligation-induced pain in rats
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DOI：
10.1093/bja/aer063
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发表时间：
2011-05-01
影响因子：
9.8
通讯作者：
Cheng, J. -K.
中科院分区：
文献类型：
--
作者：
Chu, L. -C.;Tsaur, M. -L.;Cheng, J. -K.
背景。加巴喷丁是一种抗惊厥药和辅助镇痛药。它在多项疼痛研究中有效。神经性疼痛是最难治疗的疼痛类型。在这项研究中，我们检查了鞘内注射加巴喷丁是否可以预防神经损伤引起的疼痛。方法。在异氟烷麻醉下，雄性 Sprague-Dawley 大鼠（200-250 g）接受右侧 L5/6 脊神经结扎，并放置连接至输液泵的鞘内导管。术后鞘内注射生理盐水或加巴喷丁(20μg·h(-1))7天(每组n=8)。术前（基线）确定右后爪对 von Frey 丝刺激的缩回阈值和对辐射热的缩回潜伏期，并在手术后每天一次，持续 7 天。采用苏木精-伊红和甲苯胺蓝染色评价加巴喷丁(40 μ g·h(-1))的神经毒性。结果。神经结扎后 7 天，经盐水处理的大鼠受影响的缩爪阈值和潜伏期分别从基线 11.7 (11.7-22.2) [中位数（四分位数范围）] 下降至 1.6 (0.9-3.2) g 和 10.8 (10.5-11.2) 至 4.3 (4.2-7) s。接受加巴喷丁(20μg·h(-1))的大鼠在结扎后第7天具有较高的撤退阈值[9.9(9.9-19.3)g]和潜伏期[11.5(9.7-11.9)s]。鞘内注射加巴喷丁(40μg·h(-1))后未见明显的组织病理学变化或生长迟缓。结论。我们证明了鞘内注射加巴喷丁对神经损伤引起的机械异常性疼痛和热痛觉过敏的发生具有预防作用。我们的数据表明，连续鞘内注射加巴喷丁可被视为预防神经损伤引起的疼痛的替代方案。
Background. Gabapentin is an anticonvulsant and adjuvant analgesic. It is effective in several pain studies. Neuropathic pain is the most difficult type of pain to treat. In this study, we examined if intrathecal gabapentin could prevent nerve injury-induced pain.Methods. Under isoflurane anaesthesia, male Sprague-Dawley rats (200-250 g) underwent right L5/6 spinal nerve ligation and placement of an intrathecal catheter connected to an infusion pump. After surgery, intrathecal saline or gabapentin (20 mu g h(-1)) was given for 7 days (n = 8 per group). The right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before (baseline) and once daily for 7 days after surgery. Haematoxylin and eosin and toluidine blue staining were used to evaluate the neurotoxicity of gabapentin (40 mu g h(-1)).Results. Seven days after nerve ligation, the affected paw withdrawal threshold and latency of saline-treated rats decreased from the baseline 11.7 (11.7-22.2) [median (inter-quartile range)] to 1.6 (0.9-3.2) g and 10.8 (10.5-11.2) to 4.3 (4.2-7) s, respectively. Rats receiving gabapentin (20 mu g h(-1)) had higher withdrawal threshold [9.9 (9.9-19.3) g] and latency [11.5 (9.7-11.9) s] on day 7 after ligation. No obvious histopathological change or growth retardation was detected after intrathecal gabapentin (40 mu g h(-1)) infusion.Conclusions. We showed a preventative effect of intrathecal gabapentin on the development of nerve injury-induced mechanical allodynia and thermal hyperalgesia. Our data suggest that continuous intrathecal gabapentin may be considered as an alternative for the prevention of nerve injury-induced pain.