【作者】 张慧君；

【导师】 徐军美；

【作者基本信息】 中南大学 ， 麻醉学， 2008， 硕士

【摘要】 研究背景目前关于脑源性神经生长因子(BDNF)在神经病理性疼痛和炎性疼痛中的作用研究广泛,已经初步证实BDNF是神经病理性疼痛和炎性疼痛的产生和维持中极为重要的神经递质。对于脊髓中BDNF水平的干预能起到减轻痛觉过敏的效果。然而当前对于BDNF在切割疼痛的产生维持以及切割后痛觉过敏等过程中扮演的角色仍知之甚少。而切割疼痛广泛存在于生活当中,人类深受其害,外科手术后的疼痛问题解决尚不够满意。这些都促使我们对切割疼痛的机理做更深入研究。本实验就是力图探究脊髓背角和背根神经节(DRG)中BDNF在切割疼痛发生中的作用。方法在异氟醚麻醉下纵行切割大鼠后足,在手术后不同时段取脊髓和DRG观察脊髓背角和DRG中水平变化和表达定位。分别应用免疫荧光双重标记法和免疫组织化学方法检测BDNF水平。观察利多卡因坐骨神经阻滞后对脊髓背角和DRG内BDNF水平的影响。分别在切割前一小时鞘内和腹腔内注射抗BDNF血清,观察其对切割后足大鼠的行为学改变。结果大鼠后足切割导致其同侧DRG和腰段脊髓BDNF水平上调,而胸段没有明显变化。脊髓中BDNF水平上调主要定位于神经元而不是星形胶质细胞或小胶质细胞。切割前应用局麻药利多卡因阻滞坐骨神经能够阻滞同侧DRG和腰段脊髓BDNF水平上调。鞘内注射抗BDNF血清能显著抑制切割引起的痛觉过敏。腹腔注射抗BDNF血清无上述效果。结论上述研究表明,切割导致的同侧DRG和腰段脊髓背角中BDNF水平上调与躯体感觉传入神经功能密切相关。而增高的BDNF积极参与切割诱发的痛觉过敏。更多还原

【Abstract】 Background: The pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity.Methods: A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various postoperative times (1-72 h). Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lodocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. Anti-BDNF antibody was administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal BDNF or peripheral BDNF after incision.Results: After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord. Thoracic BDNF remained unchanged in response to incision. The upregulated spinal BDNF was mainly localized in the neurons but not microglia or astrocytes. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by Incision whereas IP administration had only marginal effect.Conclusions: The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersentivity induced by surgical incision.更多还原