Podium Session

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PD01-03: Stress-induced adrenergic dysregulation alters neural-glial distribution and phenotype

Friday, May 12
7:20 AM - 7:30 AM
Location: BCEC: Room 159

Presentation Authors: Bronagh McDonnell*, Aura Kullmann, Amanda Wolf-Johnston, Anthony Kanai, Pittsburgh, PA, Peter Grace, Linda Watkins, Boulder, CO, Larissa Rodriguez, California, CA, Lori Birder, Pittsburgh, PA

Introduction: There is evidence (in patients and preclinical models) that stress can enhance painful sensations in patients with functional pain syndromes such as interstitial cystitis/bladder pain syndrome (IC/BPS). Though the underlying mechanisms have yet to be fully explored, findings reveal increased autonomic (sympathetic) dysregulation as well as a role for central augmentation. In this regard, activation of spinal cord (SC) glial cells can increase excitability of neurons leading to the initiation and maintenance of bladder hyperalgesia and impaired bladder storage function (urgency, frequency). Our goal was to examine whether chronic stress (using the water avoidance stress or WAS model) can alter neural-glial distribution and chemistry, which may play a role in micturition and pain behavior.

Methods: Adult female Wistar-Kyoto rats were exposed to WAS by placement on a pedestal in a water-filled container (1hr/day x10 consecutive days) versus handled controls. Previous published findings have revealed WAS rats exhibit long-lasting urinary frequency and hyperalgesia. SC (L6) were harvested from anesthetized animals, and either cryosectioned (for immunocytochemistry) or homogenized (for RT-PCR). The following were investigated: calcitonin gene-related peptide (CGRP; sensory fibers), microglia (IBA-1), Toll-like receptor (TLR-4), purinergic receptor subtypes (P2X4, P2X7). Separate groups of both WAS and control animals were treated 2 days prior then every other day with the adrenergic antagonist phenoxybenzamine (PB; 2 mg/kg i.p.) or saline, respectively.

Results: WAS increased neural CGRP (40%) and IBA-1 (2 fold) expression in the L6 SC dorsal horn and central canal (regions receiving input from nociceptive fibers). We find PB reduced CGRP expression (92% decrease) as well as IBA-1 in WAS SC. Further, both TLR-4 as well as P2X4 and P2X7 purinergic receptor are increased (50%) in WAS, suggesting microglia activation with chronic stress.

Conclusions: Taken together, our findings suggest increased communication between the sympathetic nervous system and bladder sensory neurons that may play an important role in chronic pain conditions. This includes abnormal neural sprouting and altered morphology and chemistry of SC glial cells, which are likely to play an important role in modifying neural activity resulting in changes in bladder function and sensory mechanisms.

Source Of Funding: AUA Urology Care Foundation Research Scholar Award. R37 DK54824. NIH RO1 DK57284

Bronagh McDonnell

My name is Bronagh McDonnell, PhD, MSc, BSc. Postdoctoral Scholar at University of Pittsburgh, PA.
I have extensive experience in a range of techniques including electrophysiology (intracellular membrane recording), whole tissue calcium imaging, immunohistochemistry, confocal microscopy, electron microscopy, histology, in-vitro tension recording, and pharmacological assessment of contractile properties using whole tissue preparations (bladder, internal anal sphincter, intestine and aorta) from a variety of species. I have experience in cell biology including cell culture, ELISA determination of proteins in human biosamples and cell superfusate. I am competent in animal handling and model generation and tissue micro-dissection. In addition to my technical abilities I am proficient in experimental design, clinical trial establishment, data analysis and interpretation, and presentation and discussion of research at lab meetings, national and international conferences, as well as mentoring of undergraduate, graduate and medical trainee researchers. My engagement and enthusiasm in research has facilitated and reinforced my understanding of visceral function at basic and clinical levels, giving me a rounded view of the problems facing patients suffering with various clinical dysfunctions and likewise, challenges faced by basic and medical researchers in finding solutions to these problems.

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PD01-03: Stress-induced adrenergic dysregulation alters neural-glial distribution and phenotype



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