Our present understanding of pain mechanisms is based primarily on experimental investigations of cutaneous pain. Less well understood are mechanisms of deep pain arising from joints, muscle and particularly the viscera. These latter sources of pain are generally more important clinically than cutaneous pain, but we know less about their mechanisms and control. Foremost among factors that have frustrated investigations of deep pain mechanisms are understanding and defining the adequate stimulus and development of models suitable for quantitative studies. This project has focused over the past several years on visceral pain, developing a reliable model that utilizes a natural, adequate, noxious stimulus, colorectal distension (CRD). Experiments proposed for the next project period will further investigate the modulation of visceral nociception and expand to focus also on afferents from the colon, spinal cellular mechanisms and supraspinal representation of visceral pain.
Specific aims i nclude: (1) continuing characterization of modulation of the pressor and visceromotor responses to noxious CRD; (2) quantitative characterization of responses of myelinated and unmyelinated pelvic nerve sensory afferents in the sacral dorsal roots to CRD; (3) an intracellular analysis of the cellular and membrane properties of spinal units that respond to CRD; and (4) characterization of visceral nociceptive unit responses supraspinally in lateral and medial thalamus, the lateral parabrachial area and the rostral, dorsal medulla.
These specific aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral pain and its modulation. The proposed experiments comprise a quantitative, parametric examination of the afferent, spinal and supraspinal physiology and local pharmacological and descending modulation of visceral nociception that will lead to better understanding of the mechanisms and control of visceral pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019912-11
Application #
3400051
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1983-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
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
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
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
Feng, Bin; Brumovsky, Pablo R; Gebhart, Gerald F (2010) Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum. Am J Physiol Gastrointest Liver Physiol 298:G402-9

Showing the most recent 10 out of 140 publications