Study on the peripheral mechanism of hyperalgesia to mechanical and cold stimulations

机械刺激和冷刺激痛觉过敏的外周机制研究

• 批准号: 11470016
• 负责人: MIZUMURA Kazue
• 金额: $ 9.28万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470016/
• 关键词: arthritis model; hyperalgesia; bradykinin; cold hyperalgesia; cutaneous nociceptor; cutaneous low threshold mechanoreceptor; mRNA; rats; 皮膚低閾値機械受容器; 侵害受容器; 火傷; アジュバント関節炎; 冷刺激; プロスタグランジンE2; ヒスタミン; B1受容体; B2受容体

The purpose of this study is to clarify the peripheral mechanisms of mechanical and cold hyperalgesia. We found :1 ) Inflammatory mediators such as bradykinin, histamine and prostaglandin E2 as well as substances that were supposed to be second messengers of these mediators, sensitized the mechanical response of canine testicular polymodal receptors in vitro.2 ) Bradykinin response of Of C-fiber nociceptors recorded in rats with adjuvant-induced polyarthritis showed more than 1000 times higher sensitivity to bradykinin. Based on the assumption that this increased sensitivity might be resulted from the increased expression of B2 bradykinin receptor in sensory neurons, we measured B2 receptor mRNA in dorsal root ganglia (DRG_s) with RT-PCR method. We found 2.5 times increase in B2 receptor in DRG_s 1 week after inoculation of adjuvant.3 ) Animals with adjuvant-induced monoarthritis showed hyperalgesia to mechanical stimulation with von Frey hairs and to mild cold stimulation with aceton drops 10-14 days after injection.4 ) Corresponding to the existence of cold hyperalgesia in monoarthritic rat the percentage of C-fiber nociceptors responding to cold stimulation up to 2℃ increased, and C-low threshold mechanoreceptors showed augmented responses to mild cold stimulation. These results suggest that increased cold sensitivity of not only nociceptors but also low threshold mechanoreceptors, which are commonly believed not to involved in nociception, play some role in hyperalgesia to cold.

本研究的目的是阐明机械性和冷痛觉过敏的外周机制，我们发现：1）炎症介质，如缓激肽、组胺和前列腺素 E2 以及被认为是这些介质第二信使的物质，使机械性痛觉过敏。犬睾丸多模式受体的体外反应。 2 ) 在佐剂诱导的多关节炎大鼠中记录的 C 纤维伤害感受器的缓激肽反应显示出更多基于这种敏感性增加可能是由于感觉神经元中 B2 缓激肽受体表达增加所致，我们采用 RT-PCR 方法测量了背根神经节 (DRG_s) 中的 B2 受体 mRNA。发现接种佐剂1周后，DRG_s中的B2受体增加了2.5倍。3）患有佐剂诱导的单关节炎的动物对机械刺激表现出痛觉过敏注射后10-14天用von Frey毛和丙酮滴进行轻度冷刺激。4）与单关节炎大鼠中冷痛觉过敏的存在相对应，C纤维伤害感受器对最高2℃的冷刺激做出反应的百分比增加，并且C -低阈值机械感受器对轻度冷刺激的反应增强。这些结果表明，不仅伤害性感受器而且低阈值机械感受器的冷敏感性也增加，而人们通常认为这并没有增加。参与伤害感受，对冷痛觉过敏发挥一定作用。

项目成果

Mizumura, K. et al.: "Thermonociception : Sensory and Modulatory Mechanisms in Pathological Conditions"In : Springer-Verlag Tokyo, "Thermotherapy for Neoplasia, Inflammation, and Pain". 550pages (2001)

Mizumura, K. 等人：“热感受：病理条件下的感觉和调节机制”，东京施普林格出版社，“肿瘤、炎症和疼痛的热疗法”。

Mizumura, K.: "Possible Contribution of Protein kinase C in the Effects of Histamine on the Visceral Nociceptor Activities in vitro"Neuroscience Research. (in press).

Mizumura, K.：“蛋白激酶 C 在组胺对体外内脏伤害感受器活性影响中的可能贡献”神经科学研究。

Mizumura,K.,Kumazawa,T.: "Thermonociception : sensory and modulatory mechanisms in pathological conditions-A review."In Kosaka,M.ed.Thermotherapy : Principles and Practice-Applications in Neoplasia, Inflammation, and Pain".Tokyo, Springer-Verlag.. 504-513

Mizumura，K.，Kumazawa，T.：“热感受：病理条件下的感觉和调节机制 - 综述。”在小坂，医学博士热疗法：肿瘤、炎症和疼痛的原理和实践应用”。东京，

Kasai,M. 他: "Increases in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal root ganglion neurons of adjuvant inflamed rats."Neuroscience Research. 39. 109-113 (2001)

Kasai, M. 等人：“佐剂发炎大鼠的背根神经节神经元对去甲肾上腺素的反应增加自发动作电位和敏感性。”神经科学研究。 39. 109-113 (2001)

Kasai, M. et al.: "Effects of PGE2 on neurons from rat dorsal root ganglia in intact and adjuvant-inflamed rats : role of NGF on PGE2-induced depolarization"Neuroscience Research. 41. 345-353 (2001)

Kasai, M. 等人：“PGE2 对完整大鼠和佐剂发炎大鼠的大鼠背根神经节神经元的影响：NGF 对 PGE2 诱导的去极化的作用”神经科学研究。