Antiallodynic effect of intrathecal neostigmine is mediated by spinal nitric oxide in a rat model of diabetic neuropathic pain
Antiallodynic effect of intrathecal neostigmine is mediated by spinal nitric oxide in a rat model of diabetic neuropathic pain
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DOI：
10.1097/00000542-200110000-00033
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发表时间：
2001-10-01
期刊：
影响因子：
8.8
通讯作者：
Pan, HL
中科院分区：
文献类型：
--
作者：
Chen, SR;Khan, GM;Pan, HL
背景：鞘内注射乙酰胆碱酯酶抑制剂可在动物和人类中产生镇痛作用，但其对糖尿病神经性疼痛的影响尚未研究。在当前的研究中，我们确定了鞘内注射乙酰胆碱酯酶抑制剂新斯的明在糖尿病神经性疼痛大鼠模型中的抗异常疼痛作用。此外，由于乙酰胆碱可以增加脊髓中一氧化氮的释放，我们研究了脊髓内源性一氧化氮在鞘内注射新斯的明治疗糖尿病神经性疼痛中的作用。 方法：通过腹腔注射链脲佐菌素 50 mg/kg 使大鼠患糖尿病。插入鞘内导管，其尖端位于腰椎鞘内空间。通过将冯弗雷丝施加到后爪来测定机械异常性疼痛。我们首先确定了鞘内注射新斯的明对异常性疼痛的剂量依赖性作用。然后通过神经元一氧化氮合酶抑制剂 (TRIM)、一氧化氮清除剂 (PTIO)、L-精氨酸或 D-精氨酸鞘内治疗来检查脊髓一氧化氮在鞘内新斯的明作用中的作用。 结果：糖尿病大鼠在注射链脲佐菌素后 4 周内出现持续的触觉异常性疼痛。鞘内注射 0.1-0.5 杯新斯的明剂量依赖性地增加了响应 von Frey 细丝应用的戒断阈值。用 30 杯 TRIM 或 30 杯 PTIO 鞘内预处理消除了鞘内新斯的明的抗异常疼痛作用。此外，鞘内注射100μg L-精氨酸而非D-精氨酸可逆转TRIM对鞘内新斯的明作用的抑制作用。结论：鞘内注射新斯的明对糖尿病神经性疼痛大鼠模型产生显着的镇痛作用。在糖尿病神经性疼痛的大鼠模型中，脊髓内源性一氧化氮有助于鞘内注射新斯的明的镇痛作用。
Background: Intrathecal administration of acetylcholinesterase inhibitors produces antinociception in both animals and humans, but their effect on diabetic neuropathic pain has not been studied. In the current study, we determined the antiallodynic effect of intrathecal injection of an acetylcholinesterase inhibitor, neostigmine, in a rat model of diabetic neuropathic pain. In addition, since acetylcholine can increase release of nitric oxide in the spinal cord, we studied the role of spinal endogenous nitric oxide in the action of Intrathecal neostigmine in diabetic neuropathic pain.Methods: Rats were rendered diabetic with an intraperitoneal 50-mg/kg injection of streptozotocin. Intrathecal catheters were inserted, with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the hind paw. We first determined the dose-dependent effect of intrathecal neostigmine on allodynia. The role of spinal nitric oxide in the action of intrathecal neostigmine was then examined through intrathecal treatments with a neuronal nitric oxide synthase inhibitor (TRIM), a nitric oxide scavenger (PTIO), L-arginine, or D-arginine.Results: The diabetic rats developed a sustained tactile allodynia within 4 weeks after streptozotocin injection. Intrathecal injection of 0.1-0.5 mug neostigmine dose-dependently increased the withdrawal threshold in response to application of von Frey filaments. Intrathecal pretreatment with 30 mug TRIM or 30 mug PTIO abolished the antiallodynic effect of intrathecal neostigmine. Furthermore, the inhibitory effect of TRIM on the action of intrathecal neostigmine was reversed by Intrathecal injection of 100 mug L-arginine but not D-arginine.Conclusions: Intrathecal neostigmine produces a profound analgesic effect in a rat model of diabetic neuropathic pain. Spinal endogenous nitric oxide contributes to the analgesic action of intrathecal neostigmine in this rat model of diabetic neuropathic pain.