Changes in neuroactive substances in a rat model of neuropathic pain and the role of hyperexcitability in neurons of spinal cord-dorsal colum-thalamus pathway

神经病理性疼痛大鼠模型中神经活性物质的变化及脊髓-背柱-丘脑通路神经元过度兴奋的作用

• 批准号: 07457007
• 负责人: NOGUCHI Koichi
• 金额: $ 4.29万
• 依托单位: HYOGO COLLEGE OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457007/
• 关键词: neuropathic pain; spinal dorsal horn; gracile nucleus; Fos; dorsal root ganglion; neuroactive substances; 末梢神経障害

The aim of this study was to examine the change in mRNA expression of inhibitory amino acid (GABAA and glycine) receptor subunits and neuropeptides in DRG of an experimental rat model of neuropathic pain. Rats received tight ligations of left L5 spinal nerves under deep anesthesia. After confirmation of the presence of neuropathic pain behaviors at 7th postoperative days, L4,5 DRG and spinal cord were dissected out for in situ hybridization and immunohistochemistry. L5 DRG neurons showed the down-regulated expression ofmRNAs of gamma2-GABAA receptor and beta1-glycine receptor subunits. Immunohistochemistry with calcitonin gene-related peptide antibody revealed that increased immunostaining in laminae III-IV of L4-5 spinal cord These data suggest that depressed inhibitory effect of amino acid and increased excitatory effect ofneuropeptide on dorsal horn neurons may contribute to the pathomechanisms of neuropathic pain.

本研究的目的是观察实验性神经病理性疼痛模型大鼠背根神经节抑制性氨基酸(GABAA和甘氨酸)受体亚基和神经肽基因表达的变化。大鼠在深度麻醉下紧密结扎左侧L5脊神经。术后第7天证实存在神经病理性疼痛行为后，取L4，5背根节和脊髓进行原位杂交和免疫组织化学染色。L5背根节神经元的Gamma2-GABAA受体和β1-甘氨酸受体亚单位的mRNAs表达下调。用降钙素基因相关肽抗体进行免疫组织化学染色，L4-5脊髓III-IV层免疫染色增强，提示氨基酸对背角神经元的抑制作用和神经肽的兴奋作用增强可能参与了神经病理性疼痛的发病机制。

项目成果

Noguchi K.et al: "Substonce Pinduced by penpleral nerve ingury in primary offevent Sonsory neurons and its effect on dorsal columin nucleus neurons" Journal of Neuroscience. 15. 9633-9643 (1995)

Noguchi K.等人：“原发性感觉神经元中侧脑神经损伤引起的物质P及其对背柱核神经元的影响”《神经科学杂志》。

Miki, K., Fukuoka, T., Tokunaga, A.and Noguchi, K.: "Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury : Up-regulation in a subpopulation of primary afferent sensory neurons"

Miki, K.、Fukuoka, T.、Tokunaga, A. 和 Noguchi, K.：“周围神经损伤后大鼠脊髓背角和背柱核中降钙素基因相关肽的增加：原发性神经损伤亚群中的上调

Noguchi, K., Kawai, Y., Fukuoka, T., Senba, E.and Miki, K.: "Substance p induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons" J.Neurosci.15. 7633-7643 (1995)

Noguchi, K.、Kawai, Y.、Fukuoka, T.、Senba, E.和 Miki, K.：“初级传入感觉神经元周围神经损伤诱导的 p 物质及其对背柱核神经元的影响” J.Neurosci

MiKi. K. et al: "CSRP nerease in the rat spinal dusal horn and dorsi/column nucleus following penpheral nerve injury,Up‐repulation" Nearoscience. (in Press).

MiKi. K. 等人：“侧脑神经损伤后大鼠脊髓杜角和背侧/柱核中的 CSRP nerease，Up-repulation”Nearoscience（出版中）。

Kashiba, H., Noguchi, K., Ueda, Y.and Senba, E.: "Coexpression of trk family members and low-affinity neurotrophin receptors in rat dorsal root ganglion neurons" Mol.Brain Res. 30. 158-164 (1995)

Kashiba, H.、Noguchi, K.、Ueda, Y. 和 Senba, E.：“大鼠背根神经节神经元中 trk 家族成员和低亲和力神经营养蛋白受体的共表达”Mol.Brain Res。