Pain Modulation and Visceral Stimulation

疼痛调节和内脏刺激

• 批准号: 6751909
• 负责人: Peggy Mason
• 金额: $ 28.5万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6751909
• 关键词: analgesia; cardiovascular function; electrocardiography; electromyography; gastrointestinal sign /symptom; heat stimulus; laboratory rat; lidocaine; lumbosacral region; microelectrodes; muscimol; neural conduction; neural information processing; neuropharmacology; pons; serotonin; visceral afferent nerve

DESCRIPTION (provided by applicant): Visceral nociception, like cutaneous nociception, is subject to descending modulatory influences from the medullary raphe magnus (RM). However, little is known about if and how RM cells contribute to: 1) visceral stimulus evoked nocifensive reactions; and 2) visceral stimulus evoked suppression of cutaneous nociception. The proposed experiments use colorectal distension (CRD) as a model visceral stimulus to explore these issues. There are 6 aims: . Aim 1A: Identify the spinal trajectory of afferents that carry ascending CRD information to RM cells. . Aim 1B: Identify the contributions of descending modulatory input, arising from RM and elsewhere, to CRD-evoked cardiovascular and visceromotor reactions. . Aim 2: Determine the effect of RM cellular inactivation on behavioral reactions to CRD. . Aim 3: Identify the physiological characteristics of neurons that discharge in a pro-nociceptive manner, with increasing excitatory responses to increasing intensities of CRD stimulation. . Aim 4: Determine the spinal pathway taken by descending modulatory input, from RM and elsewhere, to the lumbosacral spinal cord. . Aim 5: Establish the role of RM cellular activation in heterotopic suppression of cutaneous nociception by a noxious visceral stimulus. . Aim 6: Aim 3: Identify the physiological characteristics of neurons that may subserve the antinociceptive effects of CRD stimulation. The proposed experiments will test the novel hypothesis that RM's effects on spinal nociception consists of a "pro-nociceptive" component that is necessary for the normal behavioral reaction to a noxious visceral stimulus in addition to the better-studied "inhibitory modulation" component.

描述（由申请人提供）：内脏伤害感受与皮肤伤害感受一样，受到中缝大肌（RM）的下降调节影响。然而，人们对 RM 细胞是否以及如何发挥作用知之甚少：1）内脏刺激引起伤害反应； 2）内脏刺激引起皮肤伤害感受的抑制。拟议的实验使用结直肠扩张（CRD）作为内脏刺激模型来探索这些问题。 有6个目标： 。 目标 1A：识别携带上行 CRD 信息至 RM 细胞的传入神经的脊髓轨迹。 。 目标 1B：确定来自 RM 和其他地方的下行调节输入对 CRD 诱发的心血管和内脏运动反应的贡献。 。 目标 2：确定 RM 细胞失活对 CRD 行为反应的影响。 。 目标 3：确定以促伤害感受方式放电的神经元的生理特征，随着 CRD 刺激强度的增加而增加兴奋反应。 。 目标 4：确定从 RM 和其他地方到腰骶脊髓的下行调节输入所采取的脊髓通路。 。 目标 5：确定 RM 细胞激活在有害内脏刺激异位抑制皮肤伤害感受中的作用。 。 目标 6：目标 3：确定可能有助于 CRD 刺激的抗伤害作用的神经元的生理特征。 拟议的实验将检验新的假设，即 RM 对脊髓伤害感受的影响除了经过更好研究的“抑制调节”成分之外，还包含“促伤害感受”成分，该成分是对有害内脏刺激的正常行为反应所必需的。