Intracellular Dorsal Horn Mechanisms of Pain Encoding

描述：每年有数十万患者患慢性疼痛 和痛觉过敏。许多这些条件仍然很差的治疗，由于我们的 对脊髓背角的功能组织了解有限。 虽然在完整动物中的细胞外研究非常适合于定义 复杂的生理系统潜在的疼痛信号，细胞内研究， 还原制剂最适合于测定细胞过程。 作为促进我们对疼痛编码脊髓机制了解的一种手段 我们建议将这些方法结合起来。为此， 适用于完整细胞的全细胞膜片钳细胞内记录 啮齿动物背角的麻醉制备。初步研究表明， 这种方法已经揭示了神经元的新特性， 脊板例如，脊髓神经元的生物物理参数被 与他们对周围刺激的反应有关。此外，A 一种新的沉默背角细胞群已被鉴定为具有潜在的 对皮肤刺激的反应可被膜激活 去极化因此，在体内完整的动物全细胞膜片钳 代表了一种令人兴奋的新方法，用于研究细胞机制， 背角的感觉整合我们在此建议， 在浅层细胞中的初步研究，将研究扩展到 包括更深的脊髓椎板中的神经元，重要的是， 投射神经元和非投射神经元之间的生物物理差异。的 本申请中概述的研究将定义 细胞的生物物理特性影响它们的动作电位和 对自然皮肤刺激的阈下兴奋和抑制反应。 此外，我们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。这种知识是一种 关键是推进我们的知识的细胞机制的背角 感觉整合，因此将导致更好的理解和改善 急性和慢性疼痛的治疗，以及进一步了解 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.