Capsaicin Insensitive Nociceptors of the DRG

DRG 的辣椒素不敏感伤害感受器

• 批准号: 6639631
• 负责人: BRIAN Y COOPER
• 金额: $ 28.68万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639631
• 关键词: acetylcholine; action potentials; calcitonin gene related peptide; calcium ion; capsaicin; electrophysiology; heat stimulus; immunocytochemistry; membrane permeability; nociceptors; pain; potassium ion; prostaglandin E; protein kinase A; spinal ganglion; substance P; voltage /patch clamp

The development and maintenance of chronic inflammatory and neuropathic pain are often associated with functional changes in the excitability of peripheral afferents. Electrophysiological recordings on dissociated cells offer the greatest opportunity to study the mechanisms responsible for events that lead to changes in excitability. However, specific nociceptive populations in the DRG are not readily identifiable in vitro. Capsaicin sensitivity can broadly identify heat sensitive nociceptors but there is no means to readily identify subpopulation of capsaicin sensitive or capsaicin insensitive (CI) nociceptive populations of the DRG. In vivo, it has been shown that afterhyperpolarization duration (AHP) can distinguish nociceptive subpopulations from non-nociceptive populations. In our proposed investigations we will determine whether AHP distributions, observed in vivo, are maintained in vitro, and we will specifically examine and contrast the properties of CI cells with capsaicin insensitive groups with different AHPs. The experiments described we will use whole cell patch recordings on adult dissociated DRG cells. The studies have the following goals: 1) Characterization and modulation of proton activated currents in CI cells, including: an ASIC/DRASIC form of proton activated current and a TASK-like (TASK-1) current; 2) An examination of the reactivity of CI cells to heat and cold; 3) Determination of the histochemical phenotype of CI cells (IB4, SP, CGRP); and 4) To contrast the electrophysiological and immunohistochemical properties of CI and capsaicin sensitive cells.

慢性炎症和神经性疼痛的发展和维持通常与外围传入的兴奋性功能变化有关。解离细胞上的电生理记录为研究导致兴奋性变化的事件的机制提供了最大的机会。 但是，DRG中的特定伤害感受群在体外不容易识别。 辣椒素敏感性可以广泛地识别热敏感的伤害感受器，但没有能够轻松识别DRG的辣椒素敏感或辣椒素不敏感（CI）伤害感受的亚群。 在体内，已经表明，输卵管过时的持续时间（AHP）可以将伤害性亚群与非伤害性人群区分开。 在我们提出的研究中，我们将确定在体内观察到的AHP分布是否在体外观察到，我们将专门检查和对比CI细胞与辣椒素不敏感基团的特性与不同的AHP。 描述的实验我们将在成年分离的DRG细胞上使用全细胞斑块记录。 研究具有以下目标：1）CI细胞中质子激活电流的表征和调节，包括：质子激活电流的ASIC/DRASIC形式和类似任务的（任务1）电流； 2）检查CI细胞对热和冷的反应性； 3）确定CI细胞的组织化学表型（IB4，SP，CGRP）； 4）与CI和辣椒素敏感细胞的电生理和免疫组织化学特性对比。