伤害感受器
Rheobase酶
背根神经节
敏化
后超极化
神经科学
感觉系统
伤害
感觉神经元
超极化(物理学)
组胺
膜电位
化学
膜片钳
电生理学
医学
药理学
生物
内科学
受体
有机化学
核磁共振波谱
作者
Steve Davidson,Bryan A. Copits,Jingming Zhang,Guy Page,A. Ghetti,Robert W. Gereau
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2014-09-01
卷期号:155 (9): 1861-1870
被引量:135
标识
DOI:10.1016/j.pain.2014.06.017
摘要
Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. To better understand the physiology of human sensory neurons, we performed whole-cell patch-clamp recordings from 141 human dorsal root ganglion (hDRG) neurons from 5 young adult donors without chronic pain. Nearly all small-diameter hDRG neurons (<50 μm) displayed an inflection on the descending slope of the action potential, a defining feature of rodent nociceptive neurons. A high proportion of hDRG neurons were responsive to the algogens allyl isothiocyanate (AITC) and ATP, as well as the pruritogens histamine and chloroquine. We show that a subset of hDRG neurons responded to the inflammatory compounds bradykinin and prostaglandin E2 with action potential discharge and show evidence of sensitization including lower rheobase. Compared to electrically evoked action potentials, chemically induced action potentials were triggered from less depolarized thresholds and showed distinct afterhyperpolarization kinetics. These data indicate that most small/medium hDRG neurons can be classified as nociceptors, that they respond directly to compounds that produce pain and itch, and that they can be activated and sensitized by inflammatory mediators. The use of hDRG neurons as preclinical vehicles for target validation is discussed.
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