The Prolonged Analgesic Effect of Epidural Ropivacaine in a Rat Model of Neuropathic Pain
The Prolonged Analgesic Effect of Epidural Ropivacaine in a Rat Model of Neuropathic Pain
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DOI：
10.1213/01.ane.0000296460.91012.51
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发表时间：
2008-01
影响因子：
5.7
通讯作者：
Chiyo Sato;A. Sakai;Y. Ikeda;Hidenori Suzuki;A. Sakamoto
中科院分区：
文献类型：
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作者：
Chiyo Sato;A. Sakai;Y. Ikeda;Hidenori Suzuki;A. Sakamoto
背景：在临床实践中，硬膜外局部麻醉药对慢性疼痛的止痛效果有时会超过其药代动力学所预期的药物作用时间。为了研究这种持久效应的潜在机制，我们检测了局麻药罗比卡因对神经病理性疼痛模型大鼠疼痛相关行为的影响。我们还分析了神经损伤后神经生长因子(NGF)表达的变化，神经生长因子参与了伤害性环路的可塑性。方法：采用坐骨神经慢性缩窄性损伤(CCI)所致神经病理性疼痛模型，从术后第3天开始观察大鼠的热痛敏和机械性超敏反应。经硬膜外导管注入罗比卡因或生理盐水，每日1次，术后第7~13天。用酶免疫法测定L4背根神经节、后爪皮肤、L4/5背髓和坐骨神经中NGF的含量。结果：罗比卡因治疗4d后，CCI大鼠同侧足垫热刺激戒断潜伏期明显延长，热痛觉过敏基本缓解。类似地，罗比卡因治疗后，机械性异位痛觉部分减轻。应用罗比卡因的CCI大鼠，同侧L4背根节NGF含量增加，对侧则无明显变化。结论：反复向CCI大鼠硬膜外注入罗比卡因具有镇痛作用，其机制可能是通过诱导伤害性环路的可塑性改变来实现的。
BACKGROUND:In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury. METHODS:In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7–13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay. RESULTS:The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine. CONCLUSION:Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.