Intracellular Dorsal Horn Mechanisms of Pain Encoding

描述：每年有数十万患者患上慢性疼痛 和痛觉过敏。这些疾病中的许多仍然没有得到很好的治疗，因为我们的 对脊髓背角的功能组织了解有限。 尽管对完整动物的细胞外研究非常适合于定义 疼痛信号背后的复杂生理系统，细胞内研究 减量制剂最适合细胞过程的测定。 作为一种促进我们对疼痛编码脊椎机制的理解的手段 我们建议将这些方法结合起来。为此，我们有 改进型全细胞膜片钳细胞内记录 麻醉制备啮齿动物背角。对此的初步研究 方法已经揭示了浅层神经元的新特性 脊椎板。例如，脊髓神经元的生物物理参数是 与他们对外周刺激的反应相关联。此外，一个 沉默的背角细胞新群体已被确认为潜伏期 对可被膜激活的皮肤刺激的反应 去极化。因此，在完整的动物体内，全细胞膜片钳 代表了一种令人兴奋的研究细胞机制的新方法 后角的感觉整合。我们在此提议延长我们的 对浅层板层细胞的初步研究，将研究扩展到 包括更深的脊椎板中的神经元，重要的是，为了确定 投射神经元和非投射神经元之间的生物物理差异。这个 本申请中概述的研究将定义 细胞的生物物理性质影响它们的动作电位和 对自然皮肤刺激的潜意识兴奋性和抑制性反应。 此外，我们还将定义生物物理差异的离子基础 在不同功能分类的细胞之间。这类知识是一种 提高我们对背角细胞机制的认识的关键 感官整合等会带来更好的理解和提高 急慢性疼痛的治疗以及加深我们对 对躯体感觉的有意识的感知。

DESCRIPTION: Hundreds of thousands of patients each year develop chronic pain and hyperalgesia. Many of these conditions remain poorly treated due to our limited understanding of functional organization in the spinal dorsal horn. Though extracellular studies in intact animals are well suited for defining the complex physiologic systems underlying pain signaling, intracellular studies in reduced preparations are best suited for determination of cellular processes. As a means to advance our understanding of spinal mechanisms of pain encoding we propose that these approaches should be combined. To this end we have adapted whole-cellpatch clamp intracellular recording for use in an intact anesthetized preparation of the rodent dorsal horn. Initial studies with this approach have already revealed new properties of neurons in the superficial spinal lamina. For example, biophysical parameters of spinal neurons were correlated to their profile of responses to peripheral stimuli. Additionally, a novel population of silent dorsal horn cells has been identified with latent responses to cutaneous stimuli that can be activated by membrane depolarization. Thus, in viva whole cell patch clamp in intact animals represents an exciting new approach for the study of cellular mechanisms of sensory integration in the dorsal horn. We propose here to extend our preliminary studies in cells of the superficial lamina, to expand the study to include neurons in deeper spinal lamina, and importantly, to determine the biophysical differences between projection and non-projection neurons. The studies outlined in this application will define the mechanisms by which the biophysical properties of cells influence both their action potential and subliminal excitatory and inhibitory responses to natural cutaneous stimuli. Additionally we will define the ionic bases of the biophysical differences among cells of differing functional classification. Knowledge of this kind is a key to advancing our knowledge of the cellular mechanisms of dorsal horn sensory integration and so will result in a better understanding and improved treatment of acute and chronic pain as well as further our understanding of conscious perception of somatic sensation.