Transmitter release from peripheral sensory neurons

专门用于检测伤害性刺激、体温和瘙痒的外周感觉神经有其 皮肤、肌肉、骨骼和内脏的外周终末，背根神经节的胞体 (DRG)及其在脊髓背角的中央终末。刺激是由AD和C纤维携带的。 小直径感觉神经元，其中许多表达有害的热敏受体TRPV1，a 钙离子通透性阳离子通道。DRG神经元外周感觉终末中的TRPV1是一种 多种有害刺激的主要传感器，包括43oC以上的有害热刺激。尽管井很好- TRPV1存在于背角DRG神经元的中央突触终末，其 生理学上的相关性还没有明确确定。最近的发现表明，在某些情况下 条件下，TRPV1有望在核心体温(~37摄氏度)下变得活跃，远低于 TRPVI的正常激活温度阈值为43oC。第一个条件涉及相互作用 在温度和电压之间。在静止膜电位下，TRPV1显示出可测量的紧张性 激活温度为37摄氏度。随后的去极化导致TRPV1激活的大幅增加(Voet ET Al，2004)。然而，对中央终端中TRPV1功能的大多数研究都是在 室温而不是体温。第二，PLC偶联受体的激活导致 TRPVI的激活温度阈值显著降低，导致其在室温下也能被激活 温度(Chuang et al，2001)。我们建议检验这一假设，无论是生理的还是身体的 温度，在受体介导的PLC激活或生理条件下 动作电位和离子受体递质TRPV1介导的膜去极化 中枢感觉终末的激活是实质性的，这种激活将导致突触的调节 背根神经节-脊髓突触的传递。这些研究集中在疼痛通路的一个关键部分； 外周感觉纤维与中枢神经系统的交叉点，它们将提供对 在该途径中有新的调控机制。

The peripheral sensory nerves specialized for detection of noxious stimuli, temperature and itch have their peripheral terminals in the skin, muscle, bone and viscera, their cell bodies in the dorsal root ganglion (DRG), and their central terminals in the spinal dorsal horn. The stimuli are carried by AD and C-fibers of small diameter sensory neurons, many of which express the noxious heat-sensitive receptor, TRPV1, a Ca2+ permeable cation channel. TRPV1 in the peripheral sensory terminals of DRG neurons serves as a major transducer of multiple noxious stimuli, including noxious thermal stimuli above 43oC. Despite the well- established presence of TRPV1 on the central synaptic terminals of DRG neurons in the dorsal horn, its physiological relevance there has not been clearly established. Recent findings imply that under certain conditions, TRPV1 can be expected to become active at core body temperature (~37oC), well below TRPVI's normal 43oC temperature threshold for activation. The first condition involves the interaction between temperature and voltage. At resting membrane potentials, TRPV1 shows measurable, tonic activation at 37oC. Subsequent depolarization leads to substantial increases in TRPV1 activation (Voets et al, 2004). However, most investigations of TRPV1 function in central terminals have been carried out at room temperature rather than body temperature. Second, activation of PLC-coupled receptors leads to a dramatic reduction in TRPVI's temperature threshold of activation leading to its activation even at room temperature (Chuang et al, 2001). We propose to test the hypothesis that at physiological or body temperatures, and under the conditions of either receptor mediated PLC activation or physiological membrane depolarization mediated by action potentials and ionotropic receptor transmitters, TRPV1 activation in central sensory terminals is substantial and that this activation will lead to modulation of synaptic transmission at DRG-spinal cord synapses. These studies focus on a critical part of the pain pathway; the intersection of the peripheral sensory fiber with the central nervous systems and they will provide insight into new regulatory mechanisms in that pathway.