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Study on a relationship between dopamine in the substantia nigra and pain system

黑质多巴胺与疼痛系统关系的研究

基本信息

批准号：
15500241
负责人：
NISHIMORI Toshikazu
金额：
$ 2.43万
依托单位：
University of Miyazaki (2004-2005)宮崎医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To investigate the role of mesostriatal dopamine system in pain processing, we examined the withdrawal response of rat hindpaws to mechanical stimulus at 1, 4, and 12 weeks after unilateral 6-hydroxydopamine (6-HODA) lesions of the mesostriatal pathway. In all of the 6-OHDA rats examined, almost no tyrosine hydroxylase (TH) immunoreactivity was detected in the substantia nigra, ventral tegemental area, and striatum ipsilateral to 6-OHDA lesions. Alteration in the withdrawal response in this model animal was evaluated by comparing the latency of withdrawal reflex following the mechanical stimulus to the hindpaw. The latency of withdrawal response in the 6-OHDA rats was significantly reduced in the side ipsilateral to 6-OHDA lesions at all times observed, whereas that was not changed through the period observed in the contralateral side, indicating that dopamine depletion in the mesostriatal system has the influence on withdrawal response to the mechanical stimulus. These results show that the unilateral dopamine depletion causes hypersensitivity to the mechanical stumulus in the ipsilateral side, suggesting that, at least in part, dopamine in the mesostriatal system may be involved in sensory processing including pain sensation induced by mechanical stimulation.To clarify whether the hypersensitivity to mechanical stimulation in the 6-OHDA rats is derived from pain processing at the spinal cord level, Fos expression in the dorsal horn was examined following noxious mechanical stimulation to the hindpaws of this model animal. As compared with the number of Fos-positive neurons in the dorsal horn following noxious stimulation to the hindpaw of the ipsilateral and contralateral sides, there was no cleare difference in the number of Fos-positive neurons, suggesting that hypersensitivity to mechanical stimulation in 6-OHDA rats may not be caused in the spinal level.

为了研究中纹状体多巴胺系统在疼痛加工中的作用，我们在中纹状体通路单侧6-羟多巴胺（6-HODA）损伤后1、4和12周观察了大鼠后肢对机械刺激的戒断反应。在所有6-OHDA检查的大鼠中，在6-OHDA病变的同侧黑质、腹侧被盖区和纹状体中几乎没有检测到酪氨酸羟化酶（TH）免疫反应性。通过比较后爪机械刺激后的退缩反射潜伏期，评价模型动物的退缩反应变化。6-OHDA大鼠同侧6-OHDA病变的戒断反应潜伏期在所有观察时间内均显著降低，而在对侧观察时间内未发生变化，说明中纹体系统多巴胺耗竭对机械刺激的戒断反应有影响。这些结果表明，单侧多巴胺耗竭导致对同侧机械丘的超敏反应，这表明，至少在一定程度上，中纹体系统中的多巴胺可能参与了包括机械刺激引起的痛觉在内的感觉加工。为了阐明6-OHDA大鼠对机械刺激的超敏反应是否源于脊髓水平的疼痛加工，我们在对该模型动物后肢进行有害机械刺激后，检测了Fos在背角中的表达。与同侧和对侧后爪有害刺激后的背角fos阳性神经元数量相比，fos阳性神经元数量无明显差异，提示6-OHDA大鼠对机械刺激的超敏反应可能不是在脊柱水平引起的。