Impact of cholinergic plant extracts on nociception

胆碱能植物提取物对伤害感受的影响

基本信息

批准号：
6899059
负责人：
ERIC P WIERTELAK
金额：
$ 20.34万
依托单位：
MACALESTER COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2009-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This study is an initial investigation into the traditional (folk) medicine practice of using Solenace plants for pain relief. Solenace plants that will be investigated include: Atropa belladonna, Datura Stramonium, Mandragoras officinarum, Hyoscyamos niger and Solanum nigrum; each have documented use for pain relief in folk medicine. The psychoactive properties of these plants are largely attributed to concentrations of anticholinergic tropane alkaloids such as atropine, scopolamine, hyoscyamine, hyoscine and atroscine. In order to investigate the application of extracts from Solenace plants for pain relief, rat pain models will be employed, which will allow for assessment of the efficacy of these plants for pain relief beyond folk applications. Solenace plant extracts will be produced and analyzed to identify and quantify alkaloids and to determine dose-response characteristics of any alkaloid derived pain alterations. In addition to systemic, the effects of intrathecal extract administrations will be tested in three pain paradigms: hot-plate, tail-flick, and formalin tests, as spinal cholinergic circuitry has been implicated in pain responsivity. Extract and alkaloid induced alterations in pain responsivity will also be tested in animals receiving lesions of the rostral ventrpmedial medulla, a key supraspinal pain locus featuring dense muscarinic cholinergic innervation. This study will also examine the pain alterations caused by non-cholinergic hallucinogens, to determine whether changes in pain responsivity seen caused by extracts and alkaloids result from their hallucinogenic properties. Based on the results of these studies, a further investigation will focus on the development of new assays that test aspects of pain responsivity that may not be assessed by current paradigms. Together, the proposed studies will provide specific information regarding the viability, effects, and routes of action of extracts from Solenace plants in analgesic applications, and may contribute to the development of novel treatments for pain relief in humans.

描述（由申请人提供）：本研究是对使用 Solenace 植物缓解疼痛的传统（民间）医学实践的初步调查。将进行研究的茄属植物包括：颠茄、曼陀罗、曼陀罗、黑天仙和龙葵；它们在民间医学中都有用于缓解疼痛的记录。这些植物的精神活性特性很大程度上归因于抗胆碱能托烷生物碱的浓度，例如阿托品、东莨菪碱、天仙子胺、东莨菪碱和阿托菪碱。为了研究 Solenace 植物提取物在缓解疼痛方面的应用，将采用大鼠疼痛模型，这将允许评估这些植物在民间应用之外的缓解疼痛的功效。将生产并分析 Solenace 植物提取物，以鉴定和量化生物碱，并确定任何生物碱衍生的疼痛改变的剂量反应特征。除了全身试验外，鞘内提取物给药的效果还将在三种疼痛范例中进行测试：热板试验、甩尾试验和福尔马林试验，因为脊髓胆碱能回路与疼痛反应性有关。提取物和生物碱诱导的疼痛反应性改变也将在受到延髓头侧腹内侧损伤的动物中进行测试，延髓是一个关键的脊髓上疼痛部位，具有密集的毒蕈碱胆碱能神经支配。这项研究还将检查非胆碱能致幻剂引起的疼痛变化，以确定提取物和生物碱引起的疼痛反应性变化是否是由其致幻特性引起的。根据这些研究的结果，进一步的研究将集中于开发新的测定方法，以测试当前范式可能无法评估的疼痛反应性的各个方面。总之，拟议的研究将提供有关 Solenace 植物提取物在镇痛应用中的可行性、效果和作用途径的具体信息，并可能有助于开发缓解人类疼痛的新疗法。