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

本研究旨在阐明机械痛敏和冷痛敏的外周机制。结果发现：1）缓激肽、组胺和前列腺素E_2等炎症介质以及它们的第二信使物质可使犬睾丸多模态受体的机械反应增敏; 2）慢性多关节炎大鼠C纤维伤害性感受器的缓激肽反应对缓激肽的敏感性提高1000倍以上。基于这种敏感性的增加可能与感觉神经元上缓激肽B2受体表达增加有关的假设，我们用RT-PCR方法检测了背根神经节（DRG_s）中缓激肽B2受体mRNA的表达。结果发现，注射肉毒杆菌毒素1周后，背根神经节B2受体增加2.5倍。3）肉毒杆菌毒素诱发的单关节炎动物在注射肉毒杆菌毒素后10-14天，对von Frey毛的机械刺激和丙酮滴眼液的轻度冷刺激均表现出痛觉过敏。4）与单关节炎大鼠存在冷痛觉过敏相对应的是，C-受体的百分比在注射肉毒杆菌毒素后10-14天显著增加。对2℃以下冷刺激反应的纤维伤害性感受器增加，C-低阈值机械感受器对轻度冷刺激反应增强。这些结果表明，不仅伤害性感受器，而且通常认为不参与伤害性感受的低阈值机械感受器的冷敏感性增加，在冷痛觉过敏中起一定作用。

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.