Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.
Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.
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DOI：
10.1186/s12906-016-1201-2
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发表时间：
2016-07-13
影响因子：
--
通讯作者：
Choi JI
中科院分区：
文献类型：
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作者：
Yang J;Park KS;Yoon JJ;Bae HB;Yoon MH;Choi JI
由于其镇痛和抗关节炎的作用，在一些东亚国家，罂粟属植物已被用于民间医学。虽然它们的镇痛作用归因于其对电压依赖性钠通道的作用，但它们也抑制神经病理性疼痛大鼠背根神经节神经元中嘌呤能受体的表达。体外研究还表明，在小神经胶质细胞系中，黄芪抑制ATP诱导的P2 X7受体（P2 X7 R）介导的炎症反应。在本文中，我们研究了鞘内注射热处理过的马陆（PA）对大鼠脊神经结扎（SNL）模型中疼痛行为、P2 X7 R表达和小胶质细胞活化的影响。采用von Frey试验测定Sprague-Dawley大鼠L5 SNL诱导的机械性异常性疼痛，以评价鞘内注射PA的效果。采用RT-PCR和Western blot方法检测脊髓P2 X7 R表达的变化。此外，鞘内PA对小胶质细胞活化的影响通过免疫荧光进行了评价。鞘内PA以剂量依赖性方式衰减机械性异常性疼痛，显示急性和慢性效应，最大可能效应为65%。脊髓P2 X7 R的表达和产生增加后5天，但每天鞘内注射PA显着抑制增加到幼稚动物的水平。脊髓的免疫荧光显示P2 X7 R表达和激活的小胶质细胞在背角，这是抑制鞘内PA治疗的显着增加。P2 X7 R与小胶质细胞标记物共定位，但不与神经元共定位。鞘内PA可能通过抑制P2 X7 R的产生和表达以及减少脊髓中小胶质细胞的活化而在神经病理性疼痛中发挥抗异常性疼痛作用。
For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.