Ahn Dong K, Lee Sang Y, Han Seung R, Ju Jin S, Yang Gwi Y, Lee Min K, Youn Dong H, Bae Yong C
Department of Oral Physiology, School of Dentistry, Kyungpook National University, 188-1 Sam Deok 2ga, Chung-gu, Daegu 700-412, Republic of Korea.
Pain. 2009 Nov;146(1-2):114-20. doi: 10.1016/j.pain.2009.07.012. Epub 2009 Aug 7.
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 microL 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.
我们之前报道过一种在大鼠三叉神经节受压后产生慢性伤害性感受行为的新方法。在本研究中，我们进一步研究了脱髓鞘在三叉神经区域延长的伤害性感受行为发展中的作用。为此，将溶血磷脂酸（LPA）注射到体重在250至260克之间的雄性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框架上，向三叉神经节注射3微升LPA（1纳摩尔）溶液以产生脱髓鞘。这种处理降低了注射部位同侧和对侧的吹气阈值，该阈值一直持续到术后第100天，并在LPA注射后130天恢复到术前水平。LPA注射还对针刺刺激产生了明显的同侧超敏反应。还研究了LPA1/3受体拮抗剂DGPP和Rho激酶抑制剂Y-27632对LPA诱导的机械性异常性疼痛和痛觉过敏的影响。用DGPP预处理可阻断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的机械性异常性疼痛。因此，这些结果表明，靶向阻断LPA受体和Rho激酶途径可能是治疗脱髓鞘诱导的三叉神经痛样伤害感受的重要新方法。
