Intratrigeminal ganglionic injection of LPA causes neuropathic pain-like behavior and demyelination in rats
Intratrigeminal ganglionic injection of LPA causes neuropathic pain-like behavior and demyelination in rats
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DOI：
10.1016/j.pain.2009.07.012
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发表时间：
2009-11-01
期刊：
影响因子：
7.4
通讯作者：
Bae, Yong C.
中科院分区：
文献类型：
--
作者：
Ahn, Dong K.;Lee, Sang Y.;Bae, Yong C.
我们以前曾报道过一种新的方法，用于产生慢性伤害性行为的大鼠压迫三叉神经节。在本研究中，我们进一步研究了脱髓鞘在三叉神经区域长时间伤害性行为发展中的作用。为此，将溶血磷脂酸（LPA）注射到体重在250和260 g之间的雄性Sprague-Dawley大鼠的三叉神经节中。在戊巴比妥钠麻醉下，将大鼠固定在立体定位架上，并将3 μ L LPA（1 nmol）溶液注射到三叉神经节中以产生脱髓鞘。这种治疗降低了注射部位同侧和对侧的喷气阈值，持续到术后第100天，并在LPA注射后130天恢复到术前水平。LPA注射也产生了显着的同侧高反应性针刺刺激。此外，还观察了LPA 1/3受体拮抗剂DGPP和Rho激酶抑制剂Y-27632对LPA诱发的机械异常性疼痛和痛觉过敏的影响。DGPP预处理阻断了机械性异常性疼痛和同侧痛觉过敏。然而，用Y-27632预处理仅阻断同侧和对侧机械性异常性疼痛。因此，这些结果表明，LPA受体和Rho激酶通路的靶向阻断是脱髓鞘诱导的三叉神经痛样伤害性感受的潜在重要的新治疗方法。(C)2009年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
We have previously reported a novel method for producing chronic nociceptive behavior in rats following compression of the trigeminal ganglion. In the present study, we have further studied the role of demyelination in the development of prolonged nociceptive behavior in the trigeminal territory. For this purpose, lysophosphatidic acid (LPA) was injected into the trigeminal ganglia of male Sprague-Dawley rats weighing between 250 and 260 g. Under pentobarbital sodium anesthesia, the rats were mounted onto a stereotaxic frame and 3 mu L of LPA (1 nmol) solution was injected into the trigeminal ganglion to produce demyelination. This treatment decreased the air-puff thresholds both ipsilateral and contralateral to the injection site, which persisted until postoperative day 100 and returned to the preoperative levels 130 days after the LPA injection. The LPA injection also produced a significant ipsilateral hyper-responsiveness to pin-prick stimulation. The effects of DGPP, an LPA1/3 receptor antagonist, and Y-27632, a Rho kinase inhibitor, upon LPA-induced mechanical allodynia and hyperalgesia were also investigated. Pretreatment with DGPP blocked both mechanical allodynia and ipsilateral hyperalgesia. However, pretreatment with Y-27632 blocked only ipsilateral and contralateral mechanical allodynia. These results thus indicate that a targeted blockade of LPA receptor and Rho kinase pathways are potentially important new treatments for demyelination-induced trigeminal neuralgia-like nociception. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.