Electrophysiologic, pharmacologic and neurochemical techniques will be used to examine the central and peripheral mechanisms involved in bladder pain induced by the administration of irritant agents into the bladder lumen of rats and cats. The long term aim of the study is to identify the chemical signals that are involved in the neural detection, transmission and processing of noxious events in the lower urinary tract. The study will examine the mechanisms underlying the sensitization of bladder nociceptors by chemical mediators of inflammation, the central pathways for processing bladder nociceptive input, the changes in bladder reflex mechanisms induced by bladder pain and the interactions of putative afferent and efferent transmitter systems in the bladder wall. Several hypothesis will be tested: (1) that bladder pain is triggered in part by normally silent (sleeping C-fibers afferents) that are sensitized by chemical mediators released by pain producing substances, (2) that hyperalgesia defined as a painful response to a normally nonpainful stimulus can be induced in the bladder during an inflammatory state. It is noteworthy in this regard that hyperalgesia has been studied previously only in the somatic sensory system, (3) that neurochemical changes in the spinal cord similar to those induced by somatic pain will accompany acute and chronic inflammation in the urinary bladder, (4) that bladder pain will induce a reduction in bladder capacity by changes in the setpoint of the central micturition reflex pathway, and (5) that communication between afferent and efferent pathways in the peripheral nervous system represents a mechanism by which bladder irritation can influence the motility of the bladder. The long term objectives of this research program are to understand the mechanisms by which irritating or tissue-injuring stimuli in the lower urinary tract are detected and processed by the nervous system and in turn modulate lower urinary tract function. The study will utilize a multidisciplinary approach encompassing neurochemistry, electrophysiology, pharmacology and molecular neurobiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK042369-01A1
Application #
3243443
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1990-09-01
Project End
1994-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Vizzard, M A; Erdman, S L; Erickson, V L et al. (1994) Localization of NADPH diaphorase in the lumbosacral spinal cord and dorsal root ganglia of the cat. J Comp Neurol 339:62-75
Vizzard, M A; Erdman, S L; de Groat, W C (1993) Localization of NADPH-diaphorase in pelvic afferent and efferent pathways of the rat. Neurosci Lett 152:72-6
Vizzard, M A; Erdman, S L; de Groat, W C (1993) Localization of NADPH diaphorase in bladder afferent and postganglionic efferent neurons of the rat. J Auton Nerv Syst 44:85-90
Vizzard, M A; Erdman, S L; de Groat, W C (1993) The effect of rhizotomy on NADPH diaphorase staining in the lumbar spinal cord of the rat. Brain Res 607:349-53
de Groat, W C (1993) Anatomy and physiology of the lower urinary tract. Urol Clin North Am 20:383-401
Birder, L A; de Groat, W C (1993) Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT. Am J Physiol 265:R326-33
Somogyi, G T; de Groat, W C (1993) Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat. Am J Physiol 264:R1084-8
Yoshiyama, M; Roppolo, J R; Thor, K B et al. (1993) Effects of LY274614, a competitive NMDA receptor antagonist, on the micturition reflex in the urethane-anaesthetized rat. Br J Pharmacol 110:77-86
Cheng, C L; Ma, C P; de Groat, W C (1993) Effects of capsaicin on micturition and associated reflexes in rats. Am J Physiol 265:R132-8
Birder, L A; de Groat, W C (1992) Increased c-fos expression in spinal neurons after irritation of the lower urinary tract in the rat. J Neurosci 12:4878-89

Showing the most recent 10 out of 14 publications