Inflammatory influence on mechanoreceptor response

描述(申请人提供)：特定神经能量的经典理论提出，感觉信息被编码并沿着标记的线集中传输。根据这一观点，触摸、疼痛、温度(温暖、冷却)和瘙痒等皮肤感觉模式由特定类别的外周神经元编码，并通过特定的中枢神经系统通路进行传递。实验证据表明，不同感觉类别的轴突之间几乎没有足够的刺激重叠。例如，伤害性感受器不能对低强度的热和机械刺激做出反应，而机械感受器对未能刺激伤害性感受器神经元的刺激非常敏感。另一方面，关于皮肤炎症相关的变化是否能够改变非伤害性周围神经元的功能的研究很少。 皮肤慢适应I型(SAI)机械感受器对5-羟色胺和其他化学物质的反应早已为人所知，但被认为是一个没有实际意义的新奇事物。然而，最近的证据表明，机械感受器功能和炎症过程之间存在复杂的相互作用，例如，暴露于辣椒素会产生类似于轴突反射激活所引起的SAI机械感受器行为的调制。P物质、一氧化氮和前列腺素E2(以及通过肥大细胞脱颗粒的组胺和5-羟色胺)的逐渐释放似乎在炎症过程的每个阶段调节SAI机械受体的活性。 我们建议进行实验，系统地研究神经源性炎症对SAI机械感受器的影响，并使用免疫细胞化学技术来鉴定触觉穹顶内影响I型/Merkel细胞复合体的细胞元件。

DESCRIPTION (provided by applicant): The classic theory of specific nerve energies proposes that sensory information is encoded and transmitted centrally along labeled lines. According to this view, the cutaneous sensory modalities of touch, pain, temperature (warmth, cooling) and itch are encoded by specific classes of peripheral neurons and are transmitted by particular central nervous system pathways. Experimental evidence reveals little overlap of adequate stimuli between axons in different sensory categories. For example, nociceptors fail to respond to low intensity thermal and mechanical stimuli while mechanoreceptors are exquisitely sensitive to stimuli that fail excite nociceptor neurons. On the other hand, there has been little investigation of whether inflammation related changes in skin are able to alter the function of non-nociceptive peripheral neurons. Reaction of the cutaneous slowly adapting type I (SAI) mechanoreceptor to serotonin and other chemical species has long been known, but was thought to be a novelty having little practical significance. However, recent evidence now suggests a complex interaction between mechanoreceptor function and inflammatory processes such as that exposure to capsaicin produces modulation of SAI mechanoreceptor behavior similar to that induced by axon reflex activation. The progressive release of substance P, nitric oxide, and prostaglandin E2 (as well as histamine and serotonin through mast cell degranulation) appears to modulate SAI mechanoreceptor activity at each stage of the inflammatory process. We propose experiments to systematically investigate the influence of neurogenic inflammation on SAI mechanoreceptors and to use irnmunocytochemical techniques to identify the cellular elements within the touch dome that influence the type I/Merkel cell complex.