Pain Modulation and Visceral Stimulation

描述(申请人提供)：内脏伤害性感觉，就像皮肤伤害性感觉一样，受到延髓中缝大核(RM)下行调节的影响。然而，关于RM细胞是否以及如何参与：1)内脏刺激引起的伤害性反应；以及2)内脏刺激引起的皮肤伤害性抑制，我们知之甚少。拟议的实验使用结直肠扩张(CRD)作为模型内脏刺激来探索这些问题。 目标有6个： 。目的1 A：识别携带CRD上行信息至RM细胞的传入神经的脊髓轨迹。 。目的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。 。目的：研究RM细胞失活对慢性阻塞性肺疾病(CRD)行为反应的影响。 。目的3：鉴定对CRD刺激强度增加的兴奋性反应增强的伤害性放电神经元的生理特征。 。目的4：确定下行调制输入的脊髓通路，从Rm和其他部位，到达腰骶段脊髓。 。目的5：建立RM细胞激活在伤害性内脏刺激异位抑制皮肤伤害性感觉中的作用。 。目的6：目的3：确定可能有助于CRD刺激抗伤害性反应的神经元的生理特性。 拟议中的实验将检验这一新的假设，即RM对脊髓伤害性感觉的影响包括对伤害性内脏刺激的正常行为反应所必需的“前伤害性”成分，以及研究得更好的“抑制调制”成分。

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.