Study on the inflammatory mediators and intracellular signal transmission involved in the peripheral sensitization of nociceptors

伤害性感受器外周敏化过程中炎症介质及细胞内信号传递的研究

基本信息

批准号：
06680807
负责人：
MIZUMURA Kazue
金额：
$ 1.15万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Hyperalgesia is commonly observed in the inflamed region. One mechanism of the hyperalgesia is considered to be sensitization of peripheral nociceptors. The aim of this project is to clarify this sensitizing mechanism by studying 1) release of inflammatory mediators into the lightly burned (55ﾟC or 66ﾟC for 30s) air pouch, 2) effects of inflammatory mediators, especially of histamine, on the polymodal receptor, a type of nociceptor. In addition, histamine receptor subtypes and intracellular signal transmission were studied. Following results were obtained : 1) Bradykinin content in the exudate of the burned rat air pouch measured by ELISA tended to increase at 20 min after burn, peaked at 40 min, and then decreased. 2) The heat response of polymodal receptors recorded from canine in vitro superiorspermatic nerve preparations was sensitized by histamine >= 10 muM concentration-dependently. This effects was mediated through H1 receptor. To clarify involvement of protein kinase C,which is known to be activated through H1 receptor, in the histamine-induced sensitization of the heat response, effects of phorbol 12,13-dibutyrate (PDBu), a phorbol ester, was studied. PDBu excited a part of polymodal receptors >= 100 nM,and sensitized their heat response >= 10 nM concentration dependently. This sensitizing effect was blocked by treatment of staurosporine, a protein kinase inhibitor. Thus, it is highly possible that activation of protein kinase C induces sensitization of the heat response. The bradykinin response was, however, suppressed by pretreating PDBu 0.1 muM,but facilitated by simultaneously applying PDBu with bradykinin. In addition, the bradykinin response was suppressed by staurosporine. These results suggest that protein kinase C activation is implicated in the bradykinin response, and there also exist a process which is desensitized by protein kinase C.

痛觉过敏通常在发炎区域观察到，痛觉过敏的一种机制被认为是外周伤害感受器的敏化。该项目的目的是通过研究 1) 炎症介质释放到轻度烧伤（55°C）中来阐明这种敏化机制。或 66°C 30 秒）气囊，2）炎症介质（尤其是组胺）对多模式受体的影响，a此外，还对组胺受体亚型和细胞内信号传递进行了研究，得到以下结果：1)通过ELISA测定烧伤大鼠气囊渗出物中的缓激肽含量在烧伤后20分钟时趋于增加，在40分钟时达到峰值。分钟，然后下降 2) 从犬体外上精神经制剂记录的多模式受体的热响应被组胺 >= 10 敏化。 muM 依赖性。这种作用是通过 H1 受体介导的。为了澄清已知通过 H1 受体激活的蛋白激酶浓度 C，在组胺诱导的热反应敏化中的作用，佛波醇 12,13-二丁酸酯的作用。研究了佛波酯 (PDBu) 兴奋部分多模式受体 >= 100 nM，并使它们的热响应敏感化 >= 10。 nM 依赖性。星形孢菌素浓度（一种蛋白激酶抑制剂）的处理可阻断这种敏化作用，因此，蛋白激酶 C 的激活很可能会诱导热反应的敏化，然而，预处理 PDBu 0.1 会抑制缓激肽反应。 muM，但通过同时使用 PDBu 和缓激肽来促进此外，星形孢菌素抑制了缓激肽反应。这些结果表明蛋白质。缓激肽反应涉及激酶C的激活，并且还存在蛋白激酶C脱敏的过程。