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首页> 外文期刊>Life sciences >Intrathecal gabapentin and clonidine synergistically inhibit allodynia in spinal nerve-ligated rats.
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Intrathecal gabapentin and clonidine synergistically inhibit allodynia in spinal nerve-ligated rats.

机译：鞘内加巴喷丁和可乐定协同抑制脊髓神经结扎大鼠的异常性疼痛。

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AIMS: The objective of this study was to elucidate the interaction between intrathecally administered gabapentin and clonidine on neuropathic pain associated with allodynia in the spinal nerve ligation model in the rat. MAIN METHODS: Thresholds for hind paw responses to mechanical stimuli were determined by delivering von Frey filaments to the plantar surface. The left L5 spinal nerve was ligated and a fine catheter was intrathecally implanted at the L3-4 interspace under sevoflurane anesthesia. After confirmation of the established allodynia, gabapentin at 10, 30, 60 and 100mug or clonidine at 5, 15, 30 and 50mug was injected as a monotherapy in conscious rats through the intrathecal catheter to obtain the dose-response curve of %MPE (maximum possible effect) of the antiallodynic effect and its ED(50). Gabapentin and clonidine were concomitantly administered in a fixed-dose ratio proportional to the predetermined ED(50) of these drugs, thereby obtaining a dose-response curve for the drug combination and its ED(50). The profile of the interaction between these drugs was analyzed using an isobolographic analysis. KEY FINDINGS: The ED(50) for gabapentin and clonidine were 57.3+/-4.0 and 20.2+/-1.0mug, respectively (mean+/-SEM). However, the co-administration of gabapentin and clonidine at a ratio of 20:7 contributed to a much smaller experimental ED(50) values (gabapentin 10.1+/-1.1mug, and clonidine 3.6+/-0.3mug) compared with their theoretical ED(50)s on the additive line in the isobologram. SIGNIFICANCE: In the L5 spinal nerve-ligated rats, the intrathecal co-administration of gabapentin and clonidine exerted a synergistic action on the mechanical antiallodynic effect.
机译：目的：本研究的目的是阐明大鼠脊髓神经结扎模型中鞘内注射加巴喷丁和可乐定对与异常性疼痛相关的神经性疼痛的相互作用。主要方法：通过将von Frey细丝输送到足底表面来确定后爪对机械刺激的反应阈值。结扎左L5脊神经并在七氟醚麻醉下在L3-4间隙鞘内植入细导管。确认建立了异常性疼痛后，通过鞘内导管将10、30、60和100 ug的加巴喷丁或5、15、30和50 ug的可乐定作为单一疗法通过有意识的大鼠注射，获得％MPE的剂量反应曲线（最大抗痛觉过敏作用及其ED（50）。同时加巴喷丁和可乐定以与这些药物的预定ED（50）成正比的固定剂量比例给药，从而获得该药物组合及其ED（50）的剂量反应曲线。使用等效线描记分析法分析了这些药物之间的相互作用情况。主要发现：加巴喷丁和可乐定的ED（50）分别为57.3 +/- 4.0和20.2 +/- 1.0杯（均值+/- SEM）。但是，加巴喷丁和可乐定以20：7的比例共同给药，与理论值相比，其实验ED（50）值（加巴喷丁10.1 +/- 1.1mug，可乐定3.6 +/- 0.3mug）要小得多。等效线图中附加线上的ED（50）s。意义：在L5脊髓神经结扎的大鼠中，鞘内共同施用加巴喷丁和可乐定对机械性抗痛觉过敏作用具有协同作用。

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