Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
BMC Neurol. 2012 Jun 21;12:44. doi: 10.1186/1471-2377-12-44.
Amitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation (SNL)-induced neuropathic pain.
96 adult male Sprague-Dawley rats were allocated into 4 groups: group S, Sham; group L, L5 spinal nerve Ligation with vehicle treatment; group A, SNL and post-injury intra-peritoneal (Abdominal) amitriptyline twice daily × 3 days; group P, intrathecal Pretreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily × 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion (DRG) and activated glial cells in spinal dorsal horn (SDH) were measured pre-operatively and on post-operative day (POD) 4, 7, 14, 21 and 28.
SNL-evoked hyper-sensitivity responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14.
Concomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes and dysregulated Nav1.3 and 1.8.
阿米替林是一种三环类抗抑郁药，也是一种强效的钠通道利用依赖性阻滞剂，已被证明可在几种临床前模型中减轻急性和慢性疼痛。本研究的目的是研究鞘内预处理阿米替林联合损伤后腹腔内阿米替林是否比单独损伤后治疗更有效，用于治疗 L5 脊神经结扎（SNL）引起的神经病理性疼痛。
96 只成年雄性 Sprague-Dawley 大鼠分为 4 组：S 组，假手术；L 组，L5 脊神经结扎+ vehicle 处理；A 组，SNL 后+腹腔内（腹部）阿米替林每日 2 次×3 天；P 组，鞘内预处理阿米替林+ SNL+腹腔内阿米替林每日 2 次×3 天。术前和术后第 4、7、14、21 和 28 天测量热和机械刺激的反应以及损伤背根神经节（DRG）中的钠通道表达和脊髓背角（SDH）中的活化神经胶质细胞。
SNL 诱发的热和机械刺激超敏反应，DRG 中 Nav1.3 上调和 Nav1.8 下调表达，以及 SDH 中的小胶质细胞和星形胶质细胞活化。在 A 组中，腹腔内阿米替林单独使用可在 POD7 时缓解热过敏，在 POD14 时逆转 Nav1.8 并减少活化的小胶质细胞。在 P 组中，鞘内预处理阿米替林不仅增强了腹腔内阿米替林对热过敏和 Nav1.8 的作用，而且在 POD7 时减轻了机械过敏，并在 POD14 时减少了上调的 Nav1.3。此外，这种治疗方案还减少了 POD14 时星形胶质细胞的活化。
鞘内预处理联合损伤后腹腔内阿米替林治疗比单独损伤后治疗更有效，可减轻行为过敏、减少活化的小胶质细胞和星形胶质细胞以及调节 Nav1.3 和 Nav1.8。
