Visceral pain, particularly visceral hyperalgesia such as is associated with the functional bowel disorders like irritable bowel syndrome, is poorly understood. Because functional bowel disorders are characterized by increased sensitivity to gastrointestinal stimulation, pain and discomfort, they represent a visceral hyperalgesia. Increasing interest over the past decade or more has contributed significant knowledge about visceral pain mechanisms. The current application proposes to build on this base of knowledge to develop and characterize models of visceral hyperalgesia that relate closely to clinical conditions typified by irritable bowel syndrome. Specifically, this proposal will focus on examination and characterization of peripheral contributions to the development and maintenance of visceral hyperalgesia.
The first aim will be to develop appropriate models of irritable bowel syndrome and contrast those models with a model of colonic inflammation/colitis. It is hypothesized that changes in the excitability of visceral sensory fibers contribute significantly to development of visceral hyperalgesia and the second aim of this proposal will be in vivo electrophysiological examination of pelvic nerve afferent fiber excitability. Because increases in excitability of pelvic nerve sensory fibers must arise from changes in the function of ion channels or receptors in their cell bodies and terminals, the third aim of this proposal is to study the excitability of identified colon sensory neurons.
These aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral hyperalgesia. The proposed experiments comprise a quantitative study of visceral hyperalgesia, pelvic nerve sensory afferent fibers and colon sensory neurons that will lead to better understanding of the mechanisms responsible for visceral hyperalgesia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019912-21
Application #
6639370
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (01))
Program Officer
Porter, Linda L
Project Start
1983-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
21
Fiscal Year
2003
Total Cost
$367,500
Indirect Cost
Name
University of Iowa
Department
Pharmacology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Malet, Mariana; Brumovsky, Pablo R (2015) VGLUTs and Glutamate Synthesis-Focus on DRG Neurons and Pain. Biomolecules 5:3416-37
Feng, Bin; La, Jun-Ho; Schwartz, Erica S et al. (2012) Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity. Am J Physiol Gastrointest Liver Physiol 302:G676-83
La, J H; Schwartz, E S; Gebhart, G F (2011) Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K+ channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder and col Neuroscience 186:179-87
Brumovsky, Pablo R; Seroogy, Kim B; Lundgren, Kerstin H et al. (2011) Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT?-positive perineuronal baskets. Exp Neurol 230:258-72
Brumovsky, Pablo R; Robinson, David R; La, Jun-Ho et al. (2011) Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum. J Comp Neurol 519:3346-66
Tanaka, T; Shinoda, M; Feng, B et al. (2011) Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents. Am J Physiol Gastrointest Liver Physiol 300:G418-24
Schwartz, Erica S; Christianson, Julie A; Chen, Xiaowei et al. (2011) Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 140:1283-1291.e1-2
Feng, Bin; Gebhart, G F (2011) Characterization of silent afferents in the pelvic and splanchnic innervations of the mouse colorectum. Am J Physiol Gastrointest Liver Physiol 300:G170-80
La, Jun-Ho; Gebhart, G F (2011) Colitis decreases mechanosensitive K2P channel expression and function in mouse colon sensory neurons. Am J Physiol Gastrointest Liver Physiol 301:G165-74
Brumovsky, P R; Gebhart, G F (2010) Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci 153:106-15

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