CELLULAR MECHANISMS OF HYPERALGESIA

对慢性疼痛的理解和治疗仍然是一个艰巨的任务。 医学挑战痛觉过敏，一种对疼痛的反应 伤害性刺激，以及异常性疼痛，一种对伤害性刺激的反应性疼痛。 通常是无害的刺激，是持续性疼痛的两种常见形式。 拟议研究的总体目标是阐明细胞 动物痛觉过敏和异常性疼痛的潜在机制 模型系统 细胞内记录将从背角神经元中获得， 去大脑和脊髓化大鼠的脊髓， 血管系统使用非脉动泵灌注， 呼吸和心血管搏动， 记录，从而产生具有所述记录的“体内”制剂。 “体外”制剂的细胞内记录稳定性。长- 通过电刺激将诱发持久的痛觉过敏（10-60分钟 坐骨神经中的C纤维（20 s，1 Hz）。同时， 被刺穿的神经元的细胞特性的相关变化将 通过周期性地注入3s去极化脉冲来监测 通过微量移液管的电流。神经元的可塑性改变 重复点火性能将通过在点火过程中的改变来指示。 对注入电流的响应。具体目标是： 1.确定细胞特性和突触输入是否发生变化 在痛觉过敏的时候。 2.描述重复性放电中发生的特定变化 性质和离子电导。 3.比较神经元中发生的细胞变化（a）在不同的 层，（B）具有不同类型的感觉输入，（c）由 皮肤与肌肉调节C-纤维刺激，和（d）在 对Abeta、Adelta和C纤维调节刺激的反应。 这些实验将进一步加深我们对细胞机制的理解 可塑性和痛觉过敏，并可能导致改善治疗 慢性疼痛

The understanding and treatment of chronic pain remains a formidable medical challenge. Hyperalgesia, an increased pain sensation in response to noxious stimuli, and allodynia, a pain sensation in response to a normally non-noxious stimulus, are two common forms of persistent pain. The overall goal of the proposed research is to elucidate the cellular mechanisms that may underlie hyperalgesia and allodynia in an animal model system. Intracellular recordings will be obtained from dorsal horn neurons in the spinal cord of decerebrated and spinalized rats that are perfused through the vasculature. Perfusion, using a non-pulsatile pump, eliminates respiratory and cardiovascular pulsations that can disrupt intracellular recording, thereby producing an "in vivo" preparation with the intracellular recording stability of an "in vitro" preparation. Long- lasting hyperalgesia (10-60 min) will be evoked by electrical stimulation of C-fibers (20 s, 1 Hz) in the sciatic nerve. Simultaneously, the correlated changes in the cellular properties of the impaled neuron will be monitored by periodically injecting a 3 s pulse of depolarizing current through the micropipette. Plastic alterations in the neurons repetitive firing properties will be indicated by a alteration in the response to the injected current. The Specific Aims are: 1. Determine if changes in cellular properties and synaptic input occur during hyperalgesia. 2. Characterize the specific changes that occur in repetitive firing properties and ionic conductances. 3. Compare the cellular changes that occur in neurons (a) in different lamina, (b) having different types of sensory input, (c) resulting from cutaneous vs. muscle conditioning C-fiber stimulation, and (d) in response to Abeta, Adelta and C-fiber conditioning stimulation. These experiments will further our understanding of cellular mechanisms of plasticity and hyperalgesia and may lead to improved treatments for chronic pain.