DESCENDING MODULATION OF SPINAL SUBSTANTIA GELATINOSA

急性和慢性疼痛仍然是最常见的投诉， 医生被要求治疗。虽然急性疼痛可以管理在大多数 在这种情况下，医生们不断寻找新的方法， 副作用和成瘾的风险更小。慢性疼痛是一种 所有不同的物质。 据估计， 每年花费在这种疾病上的美元不包括 生产力目前，我们对慢性病的认识和治疗能力 疼痛是有限的。 本提案将研究大脑自身的 调节疼痛的能力深入了解这些机制 对于合理开发新的治疗方法至关重要， 治疗急性和慢性疼痛。持续的长期目标 这项建议的目的是确定细胞和突触机制， 这种感觉输入到背角，特别是边缘角， 区（板层I）和胶状质（板层II）的调节， 更高的大脑中心 这个五年计划的具体目标是 目的：1）继续明确局灶性脑干损伤的功能效应 对生理和解剖学上识别边缘区的刺激 和胶状质中间神经元以及边缘区神经元 确定为投射到中脑; 2）确定推定的 神经递质利用确定下行纤维通过使用 免疫细胞化学双标记技术， 电镜水平; 3）生理特性测定 抑制性中间神经元在边缘区和实质 明胶通过使用细胞内记录和标记结合 光镜和电镜免疫细胞化学标记 水平; l4）确定刺激下行系统对 原癌基因c-fos在脊髓神经元中的表达; 确定臂旁区神经元的特征， 中脑/脑桥连接，其接收来自 脊髓 这些具体目标将通过使用 联合收割机将神经元的细胞内记录与 细胞内标记，以便神经元及其轴突乔木可以被 用光学显微镜和电子显微镜检查。 推定 这些神经元中的神经递质将通过使用 光镜和电镜免疫细胞化学技术 程度.免疫细胞化学技术也将用于证明 c-fos的表达将作为细胞凋亡的标志物， 通过下行通路进行调节。

Acute and chronic pain continue to be the most common complaints which physicians are asked to treat. While acute pain can be managed in most cases, physicians are constantly searching for new methods with fewer side effects and less risk of addiction to treat it. Chronic pain is a different matter all-together. It is estimated that over 60 billion dollars are spent annually on this disorder not including loss of productivity. At present, our understanding and ability to treat chronic pain are limited. the present proposal will investigate the brain's own capacity to modulate pain. A thorough understanding of these mechanisms is essential for the rational development of new therapies for the treatment of acute and chronic pain. The continuing long term objective of this proposal is to determine the cellular and synaptic mechanisms by which sensory input to the dorsal horn and in particular the marginal zone (lamina I) and substantia gelatinosa (lamina II) is modulated by higher brain centers. The specific aims of this five year proposal are to: 1) continue to define the functional effects of focal brain stem stimulation on physiologically and anatomically identified marginal zone and substantia gelatinosa interneurons as well as marginal zone neurons identified as projecting to the midbrain; 2) determine the putative neurotransmitter utilized by identified descending fibers by using immuno-cytochemical double labeling techniques both at the light and electron microscopic level; 3) determine the physiological chacteristics of inhibitory interneurons in the marginal zone and substantia gelatinosa by using intracellular recording and labeling combined with immunocytochemical labeling both at the light and electron microscopic level;l 4) determine the effects of stimulating descending systems on the expression of the proto-oncogene, c-fos, in spinal cord neurons; 5) determine the characteristics of neurons in the parabrachial region of the midbrain/pontine junction which receive nociceptive inputs from the spinal cord. These specific aims will be accomplished by using techniques which combine intracellular recording of neurons with intracellular labeling so that the neuron and its axonal arbor can be examined with the light and electron microscopes. Putative neurotransmitters in these neurons will be assessed by using immunocytochemical techniques at both light and electron microscopic levels. Immunocytochemical techniques will also be used to demonstrate the expression of c-fos which will be used as a marker of cellular modulation by descending pathways.