Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):149-58. doi: 10.1016/j.pnpbp.2012.03.002. Epub 2012 Mar 15.
We demonstrate the establishment of a novel animal model for trigeminal neuropathic pain following compression of the trigeminal nerve root, which produces prolonged nociceptive behavior and demyelination of the trigeminal nerve root. Under anesthesia, male Sprague-Dawley rats (200-230 g) were mounted onto a stereotaxic frame and injections of a 4% agar solution (10 μl) were given to achieve compression of the trigeminal nerve root. A sham operation was performed using identical procedures but without agar injections. Nociceptive behavior was examined 3 days before and then at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after the surgery. Compression of the trigeminal nerve root caused mechanical allodynia, hyperalgesia, and cold hypersensitivity. Mechanical allodynia was established within 3 days and recovered to preoperative levels on postoperative day (POD) 40. Mechanical hyperalgesia and cold hypersensitivity persisted until 55 days following compression. The compression produced focal demyelination in the trigeminal nerve root. In the medullary dorsal horn, phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) was found to be exclusively expressed in the microglia on POD 14. Furthermore, intraperitoneal administration of carbamazepine (50mg/kg) significantly blocked mechanical allodynia and reduced p38 MAPK activation induced by the compression of the trigeminal nerve root. Our findings suggest that prolonged nociceptive behavior following compression of the trigeminal nerve root may mimic trigeminal neuralgia in this animal model and that the activation of p38 MAPK in the microglia contributes to pain hypersensitivity in rats that have undergone compression of the trigeminal nerve root.
我们建立了一种新的三叉神经根压迫性神经病理性疼痛的动物模型，该模型可导致三叉神经根的疼痛行为延长和脱髓鞘。在麻醉下，雄性 Sprague-Dawley 大鼠（200-230g）被安装在立体定向框架上，并注射 4%琼脂溶液（10μl）以实现三叉神经根压迫。假手术采用相同的程序，但不注射琼脂。在手术前 3 天和术后 3、7、10、14、17、21、24、30、40、55 和 70 天检查疼痛行为。三叉神经根压迫导致机械性痛觉过敏、痛觉过敏和冷感觉过敏。机械性痛觉过敏在术后 3 天内建立，并在术后第 40 天恢复到术前水平。机械性痛觉过敏和冷感觉过敏持续到压迫后 55 天。压迫导致三叉神经根局灶性脱髓鞘。在延髓背角，磷酸化 p38（p-p38）丝裂原激活蛋白激酶（MAPK）仅在术后第 14 天的小胶质细胞中表达。此外，腹腔内给予卡马西平（50mg/kg）可显著阻断机械性痛觉过敏，并减少三叉神经根压迫引起的 p38MAPK 激活。我们的研究结果表明，三叉神经根压迫后疼痛行为延长可能在该动物模型中模拟三叉神经痛，而小胶质细胞中 p38MAPK 的激活可能导致三叉神经根压迫大鼠的痛觉过敏。
