Pain Modulation and Visceral Stimulation

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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.