Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than 50% of females at some time in their lives. Some conditions are easy to treat, but others, such as interstitial cystitis (1C), are conditions of bladder hypersensitivity that have proven resistant to diagnosis and treatment. As demonstrated in recently published studies, the PI has examined subjects with 1C using quantitative sensory testing and found them to be hypersensitive to bladder distension and other deep tissue stimuli such as muscle pressure and ischemia. The PI of these human studies has sought to understand this urinary bladder hypersensitivity in a translational manner and so in rodents has defined basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using UBD-evoked reflexes as experimental endpoints, clinically-relevant models of bladder hypersensitivity were developed. Unfortunately, it is not known which models of bladder hypersensitivity have the greatest relevance to 1C. A critical next step in the development of model systems for translational research is to systematically test these rodent models of bladder hypersensitivity for similarity or dissimilarity to the selected disease process, 1C. In this competitive renewal the PI seeks to take this next step in translational research by concommitantly examining the effects of a non-pharmacologic, sensation-modifying manipulation known to alter the sensation of pain. Specifically, the proposal examines the effect of Heterotopic Noxious Conditioning Stimulus (HNCS) administration on sensations of humans with 1C and on reflex and neuronal responses in three mechanistically-different, rodent bladder hypersensitivity modelSi using these Aims:
Specific Aim #1 : To quantitatively compare the presence and magnitude of HNCS effects in human subjects with interstitial cystitis (1C) with matched controls.
Specific Aim #2 : To quantitatively contrast and compare the magnitude of HNCS effects in rat and murine models of bladder hypersensitivity with appropriate controls. The proposed studies examining HNCS-related effects in the 1C population and in rodent model systems by the same researcher will give insight into the comparability of models of bladder hypersensitivity with pathological processes and thereby increase the translation of basic science to therapeutics for pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK051413-11S1
Application #
7854827
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Mullins, Christopher V
Project Start
2009-07-16
Project End
2010-06-30
Budget Start
2009-07-16
Budget End
2010-06-30
Support Year
11
Fiscal Year
2009
Total Cost
$16,687
Indirect Cost
Name
University of Alabama Birmingham
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Ness, Timothy J; DeWitte, Cary; DeBerry, Jennifer J et al. (2018) Neonatal bladder inflammation alters the role of the central amygdala in hypersensitivity produced by Acute Footshock stress in adult female rats. Brain Res 1698:99-105
Ness, Timothy J; DeWitte, Cary; McNaught, Jamie et al. (2018) Spinal mechanisms of pudendal nerve stimulation-induced inhibition of bladder hypersensitivity in rats. Neurosci Lett 686:181-185
Clodfelder-Miller, Buffie J; Kanda, Hirosato; Gu, Jianguo G et al. (2018) Urothelial bladder afferent neurons in the rat are anatomically and neurochemically distinct from non-urothelial afferents. Brain Res 1689:45-53
Randich, Alan; DeWitte, Cary; DeBerry, Jennifer J et al. (2017) Lesions of the central amygdala and ventromedial medulla reduce bladder hypersensitivity produced by acute but not chronic foot shock. Brain Res 1675:1-7
Kanda, Hirosato; Clodfelder-Miller, Buffie J; Gu, Jianguo G et al. (2016) Electrophysiological properties of lumbosacral primary afferent neurons innervating urothelial and non-urothelial layers of mouse urinary bladder. Brain Res 1648:81-89
Deutsch, Georg; Deshpande, Hrishikesh; Frölich, Michael A et al. (2016) Bladder Distension Increases Blood Flow in Pain Related Brain Structures in Subjects with Interstitial Cystitis. J Urol 196:902-10
Hall, Jason D; DeWitte, Cary; Ness, Timothy J et al. (2015) Serotonin enhances urinary bladder nociceptive processing via a 5-HT3 receptor mechanism. Neurosci Lett 604:97-102
DeBerry, Jennifer J; Robbins, Meredith T; Ness, Timothy J (2015) The amygdala central nucleus is required for acute stress-induced bladder hyperalgesia in a rat visceral pain model. Brain Res 1606:77-85
Goodin, Burel R; Ness, Timothy J; Robbins, Meredith T (2015) Oxytocin - a multifunctional analgesic for chronic deep tissue pain. Curr Pharm Des 21:906-13
Korbe, Samuel; Udoji, Esther N; Ness, Timothy J et al. (2015) Ultrasound-guided interventional procedures for chronic pain management. Pain Manag 5:465-82

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