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目的探讨鞘内注射氯胺酮对慢性坐骨神经挤压损伤(CCI)大鼠脊髓背根神经节(DRG)细胞内Ca2+含量([Ca2+]i)的影响。方法雄性SD大鼠36只,随机分为3组(n=12):假手术组(Ⅰ组);CCI组(Ⅱ组);氯胺酮组(Ⅲ组)。Ⅲ组于CCI术前30min、术后1、2、3、5、7、9、11d鞘内注射氯胺酮1mg/kg,Ⅰ、Ⅱ组注射等量生理盐水。分别以vonFrey纤维丝和冷水测定触痛阈值及冷刺激反应。术后7、14d断头取L4-6双侧DRG,以流式细胞仪测定脊髓DRG细胞[Ca2+]i。结果与Ⅰ组比较,Ⅱ组术后7d术侧触痛阈值下降,冷刺激反应升高,Ⅱ组、Ⅲ组术后14d术侧触痛阈值下降,冷刺激反应升高(P<0.01或0.05);与Ⅱ组相比,Ⅲ组术后7、14d术侧触痛阈值升高,冷刺激反应降低(P<0.05)。与Ⅰ组相比,Ⅱ组术后7d双侧、Ⅱ组和Ⅲ组术后14d术侧脊髓DRG细胞[Ca2+]i升高;与Ⅱ组比较,Ⅲ组术后7d双侧及术后14d术侧脊髓DRG细胞[Ca2+]i明显降低(P<0.05或0.01)。结论鞘内注射氯胺酮治疗慢性神经痛可能与拮抗NMDA受体进而抑制脊髓DRG细胞[Ca2+]i升高有关。
Objective To investigate the effects of intrathecal ketamine on intracellular Ca2 + content ([Ca2 +] i) in the spinal cord of dorsal root ganglion (DRG) of rats with crush injury of the sciatic nerve (CCI). Methods Thirty - six male Sprague - Dawley rats were randomly divided into 3 groups (n = 12): sham operation group (group Ⅰ); CCI group (group Ⅱ); ketamine group (group Ⅲ). Group Ⅲ was given intrathecal injection of ketamine 1 mg / kg at 30 min before CCI and at 1,2,3,5,7,9 and 11 d after operation. Rats in group Ⅰ and group Ⅱ were injected with the same amount of saline. The tenderness threshold and cold stimulation response were measured with von Frey filaments and cold water respectively. L4-6 bilateral DRGs were decapitated at 7 and 14 days after operation, and the [Ca2 +] i of DRG cells in spinal cord was determined by flow cytometry. Results Compared with group Ⅰ, the pain threshold of group Ⅱ was decreased and the response of cold stimulation was increased on the 7th day after operation. In group Ⅱ and Ⅲ, the threshold of pain was decreased and the response of cold stimulation was increased on the 14th day after operation (P <0.01 or 0.05 ). Compared with group Ⅱ, the pain thresholds of group Ⅲ increased on the 7th and 14th day after operation, while the response of cold stimulation decreased (P <0.05). Compared with group Ⅰ, the level of [Ca2 +] i in DRG cells increased significantly in group Ⅱ, group Ⅱ and group Ⅲ on the 7th day after operation, compared with group Ⅰ. On the 7th day after operation, The [Ca2 +] i of DRG cells in the spinal cord on the operated side was significantly lower (P <0.05 or 0.01). Conclusion Intrathecal injection of ketamine in the treatment of chronic neuralgia may be related to the antagonism of NMDA receptor and the increase of [Ca2 +] i in spinal DRG cells.