NEUROCHEMICAL MECHANISMS OF VISCERAL PAIN

内脏疼痛的神经化学机制

• 批准号: 6187142
• 负责人: RICHARD J Traub
• 金额: $ 25.58万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187142
• 关键词: AMPA receptors; NMDA receptors; behavior test; brain electrical activity; brain mapping; central neural pathway /tract; colon; dorsal horn; gastrointestinal sign /symptom; histochemistry /cytochemistry; inflammation; inhibitor /antagonist; laboratory rat; neural information processing; neuropharmacology; pain; pain threshold; protooncogene; sensory receptors; single cell analysis; visceral afferent nerve

DESCRIPTION: (adapted from applicant's abstract) In contrast to pain of somatic origin, visceral pain has been less well studied and is poorly understood. Separate afferents encode noxious and nonnoxious somatic stimuli. However, most mechanosensitive colonic afferents respond to both noxious and innocuous mechanical stimuli and virtually all mechanosensitive colonic afferents response with thresholds below those considered painful. This application proposes to study the physiology, pharmacology and anatomy of spinal cord neurons that respond to nonnoxious and/or noxious colonic stimuli in order to examine potential strategies the nervous system uses to differentiate painful from nonpainful stimulation of the lower bowl. The long-term goal of this application is to yield a better understanding of the spinal mechanisms that produce visceral sensation in the hope of developing better therapeutic regimens for visceral pain management and ultimately the alleviation of visceral pain syndromes. A well characterized model of visceral stimulation, colorectal distention (CRD), will be used to deliver noxious or nonnoxious intensities of visceral stimulation. Behavioral, anatomical and electrophysiological techniques will be used to test several alternative, though mot mutually exclusive hypotheses in the following specific aims: 1) Test the hypothesis that behavioral and reflex responses to noxious and nonnoxious CRD in awake rats are differentiated, in part, by differences in the relative amount of activity at NMDA, AMPA and NK-1 receptors and that inflammation shifts the contribution of the receptors from the nonnoxious state to the noxious state. 2) Test the hypothesis that the population of neurons that responds to noxious CRD can be differentiated from the population of neurons that responds to nonnoxious CRD on the basis of receptor content. 3) Test the hypothesis that the differentiation of noxious from nonnoxious CRD depends on the number and target of supraspinal projection neurons. 4) Test the hypothesis that the temporal response of dorsal horn neurons contributes to the differentiation of noxious and nonnoxious CRD. Demonstrate that neurons with different temporal response profiles project to different supraspinal targets and the pharmacology of these responses differs to noxious and nonnoxious stimuli.

描述：（改编自申请人的摘要）与躯体疼痛相反 起源，内脏疼痛的研究较少，理解不足。 单独的传入编码有害和无毒的体细胞刺激。但是，大多数 机械敏感的结肠传入对有害和无害的反应 机械刺激和几乎所有机械敏感的结肠传入 阈值低于那些被认为是痛苦的阈值。此应用程序 建议研究脊髓的生理，药理学和解剖学 对无害和/或有害的结肠刺激反应的神经元 检查神经系统用来区分痛苦的潜在策略 从下碗的非刺激刺激。这个长期目标 应用是为了更好地了解脊柱机制 产生内脏的感觉，以期发展更好的治疗性 内脏疼痛管理方案，最终减轻 内脏疼痛综合征。良好的内脏刺激模型， 结直肠延伸（CRD）将用于提供有害或无情的 内脏刺激的强度。行为，解剖和 电生理技术将用于测试几种替代方案 尽管以下特定目的中的MoT互斥假设：1） 检验以下假设，即行为和反射对有害和的反应 醒着大鼠中无氧化的CRD部分是通过差异来区分的 NMDA，AMPA和NK-1受体的相对活性量， 炎症转移了受体的贡献 到有害状态。 2）检验神经元种群的假设 对有害的CRD做出回应的人可以与 根据受体含量对无氧化CRD反应的神经元。 3） 检验以下假设，即有害与无害CRD的分化 取决于脊柱上投影神经元的数量和靶标。 4）测试 假设背角神经元的时间反应有助于 有害和无害的CRD的差异。证明神经元与 不同的时间响应概况项目针对不同的脊柱上近视目标 这些反应的药理学不同于有害和无害的 刺激。