Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.
Yonsei Med J. 2013 Mar 1;54(2):321-9. doi: 10.3349/ymj.2013.54.2.321.
Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats.
Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 μg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP).
Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 μg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 μg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 μg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP.
Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.
拉莫三嗪是一种新型抗惊厥药，属于钠离子通道阻滞剂，对某些形式的神经性疼痛具有疗效。最近，小胶质细胞和星形胶质细胞的激活被认为与神经损伤诱导的神经性疼痛的发展有关。我们评估了鞘内持续给予拉莫三嗪对 L5/6 脊神经结扎诱导的神经病理性疼痛和神经胶质激活的影响。
在左侧 L5/6 脊神经结扎（SNL）后，连续鞘内给予拉莫三嗪（24、72 或 240 μg/天）或生理盐水 7 天。在手术前（基线）和术后每天一次测定左后爪对 von Frey 细丝刺激的机械性痛觉过敏。在第 7 天，通过 OX-42 抗体和胶质纤维酸性蛋白（GFAP）抗体免疫组织化学评估脊髓中小胶质细胞和星形胶质细胞的激活。
SNL 诱导生理盐水处理的大鼠出现机械性痛觉过敏，脊髓同侧 OX-42 和 GFAP 免疫反应显著增加。鞘内持续给予拉莫三嗪（240 μg/天）可预防机械性痛觉过敏，较低剂量的拉莫三嗪（72 μg/天）可改善痛觉过敏。鞘内给予拉莫三嗪（72 和 240 μg/天）抑制神经结扎诱导的小胶质细胞和星形胶质细胞激活，表现为 OX-42 和 GFAP 阳性细胞数量减少。
鞘内持续给予拉莫三嗪阻断了 SNL 诱导的机械性痛觉过敏的发展，同时抑制了小胶质细胞和星形胶质细胞的激活。鞘内持续给予拉莫三嗪可能是预防神经病变的一种有前途的治疗干预措施。
