Psychophysical Studies of Itch

瘙痒是一种常见的，有时致残的临床问题。几条证据表明， 灵长类动物的脊髓丘脑束（STT）神经元携带伤害性信息。我们最近对 灵长类STT神经元投射到腹后外侧核（VPL）， 丘脑提示这些只解释了由神经刺激引起的伤害性感受品质。但进一步 我们还需要更多的研究来完成对这些神经元的研究。该项目的一个主要目标是检查 对神经元的刺激的反应，这些神经元形成STT的几个其他主要成分， 灵长类动物我们将使用机械，热和化学刺激，包括组胺和牛 针状物-后者被认为引起组胺非依赖性瘙痒-用于心理物理学研究， 项目1中的痒。我们将识别投射到VPL或腹后下或腹后下的STT神经元， 丘脑后核的微逆向刺激方法。我们将确定的反应， 这些神经元对神经刺激的反应，并在统计学上与心理物理功能的反应相匹配， 描述由这些和其他刺激产生的瘙痒或疼痛的潜伏期、强度和持续时间。这将 使我们能够确定所检查的神经元是否特异性地或选择性地对神经元刺激或刺激产生反应。 伤害性刺激瘙痒化学品产生大面积的皮肤瘙痒（异感症）。我们将确定 STT神经元反应的变化是否可以解释皮肤瘙痒的发生。我们还将 确定是否潜在的重要类别的非常缓慢进行STT轴突，已被 在猫中描述的也存在于猴子中，如果它们对疼痛和伤害性刺激有反应。在决赛中 一系列的实验，我们将研究皮肤操作的影响，已知增加或 减少STT的瘙痒反应（包括温热、凉爽和抓挠） 神经元这些研究将有助于深入了解脊髓和丘脑的机制 潜在的瘙痒及其抑制，从而潜在地导致慢性瘙痒的改善的治疗。

Itch is a common and sometimes disabling clinical problem. Several lines of evidence indicate that spinothalamic tract (STT) neurons in primates carry pruriceptive information. Our recent search for pruriceptive (itch coding) STT primate neurons projecting to the ventral posterior lateral nucleus (VPL) of thalamus suggest that these account only for the nociceptive qualities evoked by pruritic stimuli. But further studies are needed to complete our survey of these neurons. A major goal of this project is to examine the responses to pruritic stimuli of neurons that form several of the other major components of the STT in primates. We will use mechanical, thermal and chemical pmritic stimuli including histamine and cowhage spicules -the latter believed to evoke a histamine-independent itch - that are used in psychophysical studies of itch in Project 1. We will identify STT neurons that project to either VPL or to the ventral posterior inferior or posterior nuclei of thalamus using micro-antidromic stimulation methods. We will determine the responses of these neurons to pruritic stimuli and statistically match the responses to psychophysical functions that describe the latency, intensity and duration of itch or pain produced by these and other stimuli. This will allow us to determine whether an examined neuron responds specifically or selectively to pruritic or nociceptive stimuli. Pruritic chemicals produce large areas of itchy skin (alloknesis). We will determine whether changes in the responses of STT neurons can account for occurrence of itchy skin. We will also determine whether the potentially important class of very slowly conducting STT axons that have been described in cats also exist in monkeys and if they respond to pruritic and nociceptive stimuli. In the final series of experiments, we will examine the effects of cutaneous manipulations that are known to increase or decrease the sensation of itch (including warming, cooling, and scratching) on pruritic responses of STT neurons. These studies should provide insight into to the mechanisms in both the spinal cord and thalamus underlying itch and its inhibition, and, thereby, potentially lead to improved treatments of chronic itch.