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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037424-03
Application #
6393919
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (01))
Program Officer
Porter, Linda L
Project Start
1999-08-01
Project End
2003-05-31
Budget Start
2001-08-01
Budget End
2003-05-31
Support Year
3
Fiscal Year
2001
Total Cost
$227,450
Indirect Cost
Name
University of Maryland Baltimore
Department
Dentistry
Type
Schools of Dentistry
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Ji, Yaping; Hu, Bo; Li, Jiyun et al. (2018) Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats. J Pain 19:764-776
Cao, Dong-Yuan; Bai, Guang; Ji, Yaping et al. (2016) EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats. Mol Pain 12:
Ji, Y; Bai, G; Cao, D-Y et al. (2015) Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats. Neurogastroenterol Motil 27:775-86
Cao, Dong-Yuan; Bai, Guang; Ji, Yaping et al. (2015) Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity. Gut 64:1913-20
Traub, Richard J; Cao, Dong-Yuan; Karpowicz, Jane et al. (2014) A clinically relevant animal model of temporomandibular disorder and irritable bowel syndrome comorbidity. J Pain 15:956-66
Traub, Richard J; Ji, Yaping (2013) Sex differences and hormonal modulation of deep tissue pain. Front Neuroendocrinol 34:350-66
Cao, Dong-Yuan; Ji, Yaping; Tang, Bin et al. (2012) Estrogen receptor ? activation is antinociceptive in a model of visceral pain in the rat. J Pain 13:685-94
Ji, Yaping; Tang, Bin; Cao, Dong-Yuan et al. (2012) Sex differences in spinal processing of transient and inflammatory colorectal stimuli in the rat. Pain 153:1965-73
Ji, Yaping; Tang, Bin; Traub, Richard J (2011) Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a visceral pain model in the rat. Pain 152:1182-91
Murphy, Anne Z; Suckow, Shelby K; Johns, Malcolm et al. (2009) Sex differences in the activation of the spinoparabrachial circuit by visceral pain. Physiol Behav 97:205-12

Showing the most recent 10 out of 24 publications