Spatial Properties of Cutaneous Temperature Sensitivity

描述(申请人提供)：在动物模型中热接受的生理学、神经生物学和分子生物学方面的进展已经超过了对人类热接受的研究。目前正在进行的项目试图将这一新知识纳入心理物理学研究，以测试关于人类温度敏感性基本机制的假设。该项目之前的研究发现，有证据表明，经典定义的冷暖感觉和痛觉之间的敏感度存在广泛重叠，触觉和温度之间的相互作用改变了温度感知的定性和定量维度。这项拟议的研究建立在这些和其他更新的发现的基础上，以调查不痛的温度是如何通过皮肤感觉系统之间的多感觉相互作用来感觉的。具体地说，Aim 1将测试一个简单的模型，了解低阈值热传入纤维如何会聚，并与脊髓丘脑束中的热和伤害性感觉神经元相互作用。该模型的测试部分基于心理物理学证据，即在热纤维和冷纤维范围内敏感的传入纤维可以将刺激传递到疼痛通路，将提供关于非痛热机制的基本信息，以及假定的热纤维和冷纤维对热痛和冷痛阈值的可能贡献。目的2将测试有关最近发现的瞬时受体电位(Trp)通道参与非痛觉冷热知觉的假说，使用已被证明调节这些通道的化学制剂的局部应用。最后，目标3将研究触觉刺激的参数，这些参数是简单接触抑制热敏感性的基础，特别是在无害的温度下感知的伤害性感觉。有趣的是，这种抑制是来自于触摸对疼痛的一般抑制作用，还是来自于减弱对接触热刺激的敏感性的特殊机制。通过测试关于温度敏感性与疼痛关系的新假说，这项拟议的研究将提供有关疼痛系统的所有兴奋性热输入以及热和触觉系统对疼痛系统施加的全面抑制控制的新信息。因此，该项目有可能为躯体感觉和疼痛系统之间正常相互作用的中断如何在纤维肌痛、多发性硬化症和中风等临床疾病的神经病理性疼痛的发展中发挥作用提供新的见解。公共卫生相关性：拟议的研究将提供关于人类对温度的敏感性及其与疼痛的关系的新的基本信息。心理物理学方法将被用来调查神经模型做出的预测，即感觉到非疼痛刺激的外周神经元可能如何与中枢神经系统中服务于痛感的神经元相互作用。特别是，实验将测试一些假设，即对温和的降温、加热或触摸做出反应的外周神经元是否会兴奋或抑制脊髓丘脑束中的伤害性神经元。通过测试关于温度敏感性与疼痛关系的新假设，拟议的项目有可能为温和温度引发的疼痛神经病的原因提供见解，如与多发性硬化症、纤维肌痛和中风有关的疾病。

Description (provided by applicant): Advances in the physiology, neurobiology, and molecular biology of thermoreception in animal models have outpaced research on human thermoreception. The present continuing project seeks to incorporate this new knowledge into psychophysical studies that test hypotheses about basic mechanisms of human temperature sensitivity. Previous research on the project uncovered evidence of an extensive overlap in sensitivity between the classically defined senses of warmth and cold and the sense of pain, and of interactions between touch and temperature that modify the qualitative and quantitative dimensions of temperature perception. The proposed research builds on these and other more recent findings to investigate how nonpainful temperatures are sensed via multisensory interactions among the cutaneous sensory systems. Specifically, Aim 1 will test a simple model of how low-threshold thermal afferent fibers may converge and interact with thermal and nociceptive neurons in the spinothalamic tract. Tests of the model, which is based in part on psychophysical evidence that afferent fibers with sensitivities in the range of warm fibers and cold fibers can relay stimulation to the pain pathway, will provide basic information about the mechanisms of nonpainful heat and the possible contribution of putative warm fibers and cold fibers to the thresholds for heat pain and cold pain. Aim 2 will test hypotheses about the involvement of recently discovered transient receptor potential (TRP) channels in nonpainful perception of cold and heat using topical application of chemical agents that have been shown to modulate these channels. Finally, Aim 3 will investigate the parameters of tactile stimulation that underlie the ability of simple contact to suppress thermal sensitivity, particularly nociceptive sensations perceived at innocuous temperatures. Of interest is whether this suppression arises from a general inhibitory action of touch on pain or from a specialized mechanism that attenuates sensitivity to contact thermal stimulation. By testing novel hypotheses about the relationship of temperature sensitivity to pain, the proposed research will yield new information about the full range of excitatory thermal inputs to the pain system as well as the full range of inhibitory controls which the thermal and tactile systems exert on the pain system. The project therefore has the potential to provide new insights into how disruption of normal interactions between the somesthetic and pain systems may play a role in the development of neuropathic pain in clinical disorders such as fibromyalgia, multiple sclerosis, and stroke. PUBLIC HEALTH RELEVANCE: The proposed research will provide new, basic information about the human sensitivity to temperature and its relationship to pain. Psychophysical methods will be used to investigate predictions made from a neural model of how peripheral neurons that sense nonpainful stimuli may interact with neurons in the central nervous system that serve the sense of pain. In particular, experiments will test hypotheses about whether peripheral neurons that respond to mild cooling, heating or touch may excite or inhibit nociceptive neurons in the spinothalamic tract. By testing new hypotheses about the relationship of temperature sensitivity to pain the proposed project has the potential to provide insights into the causes of painful neuropathies that can be triggered by mild temperatures, such as those associated with multiple sclerosis, fibromyalgia, and stroke.