OPIOID CELL TRANSPLANTS FOR PAIN ALLEVIATION

描述：(申请人摘要) 将细胞或组织移植到中枢神经系统是一种潜在的方法 实现天然衍生药理活性物质的持续递送 用于缓解慢性病的物质。在我们的实验室工作 已经证明肾上腺髓质细胞或嗜铬细胞移植 脊椎蛛网膜下腔可以减轻几种动物的疼痛症状 模特们。这很可能涉及到减轻疼痛的神经活性物质的释放 阿片肽和儿茶酚胺等物质，来自 移植的细胞。移植方法的一个显著优势是 慢性疼痛患者的潜在能力是提供持续的 可再生的止痛药来源，减少或消除对 反复使用麻醉剂。由于有希望的发现在 动物研究和临床研究已于#年在几个中心启动。 癌症疼痛患者，结果令人鼓舞。世界银行的目标是 拟议的研究是为了了解机制、长期后果、 以及这些移植在中枢神经系统的潜在局限性。药理学 将进行生化分析，以确定移植 与宿主脊髓受体的相互作用，阿片类药物和 其他神经肽能减轻疼痛，并能耐受和交叉耐受 传统的药物疗法。植物移栽的机理 减少急性和慢性疼痛过程可能是不同的，也将是 使用选择性伤害性感受器激活和急性和慢性疼痛进行评估 模特们。据认为，慢性疼痛，如由此导致的 周围神经损伤或炎症是由一连串的 导致持续性过度兴奋的神经病理事件，包括 N-甲基-D-天冬氨酸受体的激活与一氧化氮和环磷酰胺的产生 GMP。临床上，尽管在疼痛管理方面取得了进展，但一些最 衰弱障碍是与外周或中枢神经相关的疾病。 损害和慢性炎症，控制不佳或不充分 通过传统的药物疗法。我们实验室最近的研究表明 提示肾上腺髓质细胞或嗜铬细胞移植可以 缓解周围神经损伤引起的慢性疼痛症状和 炎症，并可能通过干预NMDA/NO级联来实现。因此， 如果成功，这些研究的发现可能会导致一部小说 长期治疗干预缓解慢性阻塞性肺疾病的探讨 慢性疼痛综合征，尤其是那些对传统疗法无效的 药物治疗，谁将从改善生活质量中受益 没有痛苦。

DESCRIPTION: (Applicant's Abstract) The transplantation of cells or tissue into the CNS is a potential means of achieving sustained delivery of naturally derived pharmacologically active substances for the alleviation of chronic disorders. Work in our laboratory has demonstrated that adrenal medullary or chromaffin cell transplants in the spinal subarachnoid space can alleviate pain symptoms in several animal models. This most likely involves the release of pain-reducing neuroactive substances, such as opioid peptides and catecholamines, from the transplanted cells. A significant advantage of the transplant approach for the chronic pain patient is the potential ability to provide a continually renewable source of analgesic agents, reducing or eliminating the need for repeated narcotic administration. As a result of promising findings in animal studies, clinical studies have been initiated at several centers in patients with cancer pain, with encouraging results. The goals of the proposed studies are to understand the mechanisms, long-term consequences, and potential limitations of these transplants in the CNS. Pharmacologic and biochemical analyses will be done in order to determine transplant interactions with host spinal receptors, the contribution of opioid and other neuropeptides to pain reduction, and tolerance and cross-tolerance to traditional pharmacotherapies. The mechanisms of the transplants in reducing both acute and chronic pain processes may be distinct, and will be evaluated using selective nociceptor activation and acute and chronic pain models. It is thought that chronic pain such as that consequent to peripheral nerve injury or inflammation results from a cascade of neuropathological events leading to persistent hyperexcitability, including activation of NMDA receptors and the production of nitric oxide and cyclic GMP. Clinically, in spite of advances in pain management, some of the most debilitating disorders are those associated with peripheral or central nerve lesions and chronic inflammation, and are poorly or inadequately controlled by traditional pharmacotherapies. Recent studies in our laboratory have suggested that adrenal medullary or chromaffin cell transplants can alleviate symptoms of chronic pain due to peripheral nerve injury and inflammation, and may do so via intervening in the NMDA/NO cascade. Thus, if successful, the findings from these studies could lead to a novel approach in the long term therapeutic intervention for alleviation of chronic pain syndromes, particularly those refractory to traditional pharmacotherapies, who would benefit greatly by improved quality of life free from pain.