Psychophysical Studies of Itch

伤害感受神经元的化学激活可能导致许多中枢神经系统疾病中的慢性瘙痒和疼痛。 神经系统在上一个资助期间，我们确定，养牛产生痒的非？ 组胺能的机制，我们确定了奶牛的过敏剂是一种半胱氨酸蛋白酶。 内源性蛋白酶可能导致临床瘙痒和疼痛。在其他刺激因素中，使用新的 一种点状施用化学品的方法，所述化学品已装载到热灭活的 cowhage，我们将精神病学测量人类的瘙痒，疼痛和皮肤瘙痒（增强的瘙痒或疼痛） 志愿者我们的目标如下：（1）我们将确定是否瘙痒，疼痛和皮肤感觉迟钝， （增强的瘙痒或疼痛）来自机械或化学刺激的点状应用，如 内源性半胱氨酸蛋白酶，由辣椒素敏感的初级传入神经元介导;（2）我们将 测试组胺能和非组胺能通路的共激活是否导致延长或 增强疼痛和伤害性感觉和感觉迟钝;（3）研究其抑制作用 抓挠，加热和致痛化学物质对瘙痒，疼痛和发痒的皮肤，而戏弄分开的单独 刺激方式（激活的神经元类型）、位置和强度的作用。(4)我们将我们的压力块 有髓神经纤维的传导，以检查有髓与无髓伤害感受器的不同作用。 化学和机械诱发的瘙痒、伤害性感觉和感觉迟钝中的有髓鞘轴突。的 这些研究的结果将增加对瘙痒和疼痛以及感觉迟钝状态如何影响人类的理解。 存在于某些临床疾病中;以及一种或另一种感觉质量或感觉障碍状态如何被 增强或抑制。这些对人类的心理物理学研究将提供一套感官条件， 必须通过候选的伤害感受和伤害感受特异性感觉神经元的反应来解释 在外周和中枢神经系统中。 相关性（参见说明）： 对人类实验产生的瘙痒、疼痛和瘙痒皮肤的心理物理测量将进一步促进我们的研究。 了解导致临床瘙痒的感觉条件，并指出其潜在的神经 机制等这些机制为未来的药物治疗提供了靶点， 瘙痒和疼痛。

Chemical activation of nociceptive neurons may contribute to chronic itch and pain in many disorders of the nervous system. During the last funding period, we determined that cowhage produces itch by a non¿ histaminergic mechanism, and we identified the pruritic agent in cowhage to be a cysteine protease. Endogenous proteases may contribute to clinical pruritus and pain. Using, among other stimuli, a new method of punctate application of a chemical that has been loaded into a heat-inactivated spicule of cowhage, we will psychophysically measure itch, pain and itchy skin (enhanced itch or pain) in human volunteers. Our aims are the following: (1) We will determine whether itch, pain, and cutaneous dysesthesias (enhanced itch or pain) from punctate application of mechanical or chemical pruritic stimuli such as an endogenous cysteine protease, are mediated by capsaicin sensitive primary afferent neurons; (2) We will test whether co-activation of the histaminergic and non-histaminergic pathways leads to the prolongation or enhancement of pruritic and nociceptive sensations and dysesthesias; (3) We will study the inhibitory effects of scratching, heating and algogenic chemicals on itch, pain and itchy skin while teasing apart the separate roles of stimulus modality (type of neuron activated), locus and intensity. (4) We will us a pressure block of conduction in myelinated nerve fibers to exam the separate roles of nociceptors with myelinated vs. non¿ myelinated axons in chemically and mechanically evoked itch, nociceptive sensations and dysesthesias. The outcomes of these studies will increase understanding of how itch and pain and dysesthetic states can co¿ exist as in certain clinical disorders; and how one or another sensory quality or dysesthetic state can be enhanced or inhibited. These psychophysical studies in human will provide a set of sensory conditions that must be accounted for by the responses of candidate pruriceptive and nociceptive-specific sensory neurons in the peripheral and central nervous system. RELEVANCE (See instructions): Psychophysical measurements of experimentally produced itch, pain and itchy skin in humans will further our understanding of the sensory conditions contributing to clinical pruritus and point to their underlying neural mechanisms. These mechanisms provide targets for future pharmacological therapies designed to relieve itch and pain in humans.