BERKELEY, CA (UroToday.com) - Visceral pain conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS), are some of the most poorly understood clinical diagnoses.
In order to learn more about the etiology of IC/BPS, basic researchers have been attempting to create clinically relevant animal models that mimic the condition. Traditionally cystitis and resulting bladder nociception have been produced by intravesicular instillation of chemical irritants such as acetone, hydrochloric acid, and mustard oil. In order to determine the relative “pain” levels of infected animals, experimenters monitored nocifensive responses like bladder voiding, immobility and breathing rates. The most definitive indications of bladder-derived nociception in these models however are the histological and morphological changes observed in the bladder which can only be detected following animal death.
In this article, we present step-by-step directions for performing urinary bladder distension (UBD) in mice. In this model, compressed air is blown into the bladder of an anesthetized mouse in 20-second intervals (see figure). Electrical output from the external oblique abdominal muscle is measured throughout the 20-second distension and used as a pain indicator. This electrical activity, known as the visceromotor response (VMR), is inhibited following intravesicular lidocaine administration and increased following mustard oil sensitization of the bladder.[1] Furthermore, VMRs intensify with increasing bladder pressure.[1] This quality allows experimenters to determine if experimental manipulations (e.g., drug administration, electrical stimulation, etc.) affect bladder nociception. Unlike the indirect nocifensive behavior measurement, VMRs are direct, reliable, reproducible measures of bladder nociception.
UBD has been used to investigate the role of the central and peripheral nervous systems in bladder pain processing.[2, 3, 4] Through pharmacological and genetic manipulations, experimenters have been able to learn more about bladder pain processing in the spinal cord and brain regions such as the central amygdala and rostral ventromedial medulla. Additionally, UBD has been used to explore molecular patterns of the urothelium and resulting bladder sensitization.[5] To learn more about the cellular and physiological aspects of IC/BPS, UBD is an indispensable research tool. For that reason, we elected to publish this paper in JoVE, the Journal of Visualized Experiments. JoVE is a peer-reviewed video journal that provides readers with step-by-step directions, narrated videos, descriptive materials list, and representative results for all published procedures. For naïve experimenters, these video publications are invaluable tools that are only second bested by real-life instruction. It is our hope that by publishing UBD in this format, reproducibility and translatability of results obtained using UBD will increase.
References:
- Ness, T. J. & Elhefni, H. Reliable visceromotor responses are evoked by noxious bladder distension in mice. J Urol 171, 1704-1708 (2004).
- Crock, L. W. et al. Central Amygdala Metabotropic Glutamate Receptor 5 in the Modulation of Visceral Pain. Journal of Neuroscience 32, 14217-14226, doi:10.1523 (2012).
- Lai, H. H. et al. Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder. Pain 152, 2117-2124, doi:10.1016/j.pain.2011.05.017 (2011).
- Yang, M. et al. GLT-1 overexpression attenuated bladder nociception and local/cross-organ sensitization of bladder nociception. Am J Physiol Renal Physiol 300, F1353-F1359, doi:10.1152/ajprenal.00009.2011.-Glutamatergic (2011).
- Stemler, K. M. et al. Protamine sulfate induced bladder injury protects from distention induced bladder pain. J Urol 189, 343-351, doi:10.1016/j.juro.2012.08.189 (2013).
Written by:
Benedict J. Kolber, PhD* and Katelyn Sadler, PhD student as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
*Assistant Professor
Department of Biological Sciences and
Research and Education Coordinator
Chronic Pain Research Consortium
Duquesne University
600 Forbes Avenue
Pittsburgh, PA USA
Urinary bladder distention evoked visceromotor responses as a model for bladder pain in mice - Abstract