DESCENDING MODULATION OF SPINAL SUBSTANTIA GELATINOSA

急性和慢性疼痛仍然是最常见的主诉， 医生被要求进行治疗。虽然急性疼痛在大多数情况下都可以控制 在这种情况下，医生们不断地寻找新的方法，用更少的 副作用和较少的成瘾风险来治疗。慢性疼痛是一种 不同的事情都在一起。据估计，超过600亿美元 每年花费在这种疾病上的美元不包括 生产力。目前，我们对慢性阻塞性肺疾病的认识和能力 痛苦是有限的。目前的建议将研究大脑自身 调节疼痛的能力。对这些机制的透彻了解 对于合理开发治疗癌症的新疗法是必不可少的 急慢性疼痛的治疗。持续的长期目标 这一建议的目的是通过以下方式确定细胞和突触机制 什么感觉输入到后角，特别是边缘 区(板层I)和胶状质(板层II)受 更高级的大脑中心。这项五年计划的具体目标是 目的：1)继续确定局灶性脑干的功能效应 对生理和解剖识别的边缘地带的刺激 和胶状质中间神经元以及边缘带神经元 被识别为投射到中脑；2)确定假定的 识别出的下行纤维利用的神经递质 免疫细胞化学双重标记技术在光和 电子显微镜水平；3)生理特性测定 在边缘区和实质内的抑制性中间神经元 用细胞内记录和标记结合 光镜和电子显微镜的免疫细胞化学标记 L 4)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 臂旁核区神经元特征的测定 接受伤害性信息的中脑/桥脑连接部 脊髓。这些具体目标将通过使用 将神经元的细胞内记录与 细胞内标记，使神经元及其轴突可以 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 光镜和电子显微镜下的免疫细胞化学技术 级别。免疫细胞化学技术也将用于证明 C-fos基因的表达可作为细胞分化的标志物 通过下行通路进行调制。

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.