CELLULAR MECHANISMS OF HYPERALGESIA

对慢性疼痛的理解和治疗仍然是一项艰巨的任务 医学挑战。痛觉过敏，一种增加的痛觉反应 对有害的刺激，和超敏，一种对疼痛的反应 通常，非伤害性刺激是持续性疼痛的两种常见形式。 这项拟议研究的总体目标是阐明细胞 动物痛觉过敏和痛敏的可能机制 模型系统。 细胞内的记录将从背角神经元获得 去大脑和去脊髓化大鼠的脊髓通过 血管系统。使用非脉动泵的灌流，消除了 可扰乱细胞内的呼吸和心血管搏动 记录，从而产生一种具有 “体外”制剂的细胞内记录稳定性。长- 电刺激可引起持续性痛觉过敏(10-60分钟) C纤维(20 S，1赫兹)在坐骨神经中的分布。同时， 被刺穿的神经元细胞特性的相关变化将 通过周期性注入3个S去极化脉冲进行监测 电流流过微吸管。神经元的可塑性改变 重复性激发属性将通过更改 对注入电流的响应。具体目标是： 1.确定细胞属性和突触输入是否发生变化 在痛觉过敏期间。 2.描述重复激发过程中发生的具体变化 性质和离子导电性。 3.比较不同年龄段神经元(A)的细胞变化 板层，(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) 对Aβ、Aβ和C纤维条件性刺激的反应。 这些实验将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.