Psychophysical Studies of Itch

伤害性神经元的化学激活可能导致慢性瘙痒和疼痛的许多疾病 神经系统。在上一次资助期间，我们确定母牛产生瘙痒的是非？ 组胺能机制，我们鉴定牛饲料中的瘙痒因子是一种半胱氨酸蛋白酶。 内源性蛋白水解酶可能与临床瘙痒和疼痛有关。在其他刺激措施中，使用一种新的 一种点状涂抹化学物质的方法，该化学物质已加载到热灭活的针叶中 我们将在心理生理上测量人类的瘙痒、疼痛和皮肤瘙痒(加剧的瘙痒或疼痛)。 志愿者。我们的目标是：(1)我们将确定瘙痒、疼痛和皮肤感觉不良 (加剧的瘙痒或疼痛)点状应用机械或化学的瘙痒刺激，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同激活是否导致延长或 增强瘙痒和伤害性感觉和感觉障碍；(3)我们将研究抑制作用 在瘙痒、疼痛和瘙痒的皮肤上抓挠、加热和致敏化学物质，同时梳理分开的 刺激方式(激活的神经元类型)、部位和强度的作用。4.我们将对……施加压力 有髓神经纤维传导以检测有髓与无髓伤害性感受器的不同作用 化学和机械诱发的瘙痒、伤害性感觉和感觉障碍中的有髓轴突。这个 这些研究的结果将增加对瘙痒、疼痛和感觉障碍状态如何相互影响的理解 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 增强的或抑制的。这些人体心理物理研究将提供一套感官条件， 必须由候选的瘙痒和伤害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(请参阅说明)： 对实验产生的人类瘙痒、疼痛和皮肤瘙痒的心理物理测量将进一步推动我们的 了解导致临床瘙痒的感觉条件，并指出其潜在的神经 机械装置。这些机制为未来的药物治疗提供了靶点，旨在缓解 人类的瘙痒和疼痛。

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.