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 1 A: Identify the spinal trajectory of afferents that carry ascending CRD information to RM cells. .
Aim 1 B: 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS043329-01A2
Application #
6687034
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Porter, Linda L
Project Start
2003-06-01
Project End
2008-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$277,980
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Mason, Peggy (2012) Medullary circuits for nociceptive modulation. Curr Opin Neurobiol 22:640-5
Hellman, Kevin M; Brink, Thaddeus S; Mason, Peggy (2007) Activity of murine raphe magnus cells predicts tachypnea and on-going nociceptive responsiveness. J Neurophysiol 98:3121-33
Brink, Thaddeus S; Hellman, Kevin M; Lambert, Aaron M et al. (2006) Raphe magnus neurons help protect reactions to visceral pain from interruption by cutaneous pain. J Neurophysiol 96:3423-32
Brink, Thaddeus S; Mason, Peggy (2004) Role for raphe magnus neuronal responses in the behavioral reactions to colorectal distension. J Neurophysiol 92:2302-11