Date of Completion

2016

Document Type

Honors College Thesis

Department

Neurological Sciences

Type of Thesis

Honors College, College of Arts and Science Honors

First Advisor

Sayamwong Hammack

Second Advisor

Margaret Vizzard

Third Advisor

Donna Toufexis

Keywords

PACAP; RVS; urinary bladder; DRG; TRPV1; TRPV4

Abstract

Stress can cause or contribute to bladder dysfunction though specific effects remain unclear. Individuals with interstitial cystitis (IC)/bladder pain syndrome (BPS) experience increased symptom severity with stress, including pain and increased urgency and frequency of voiding. Further research can identify stress-related changes to urinary mechanisms, such as changes in sensory neurotransmitters and subsequent receptor expression. These factors could then become targets for future therapies providing bladder dysfunction relief. Alterations in PACAP and TRPV channel expression have been shown in sensory pathways in response to disease. My research studied the effects of chronic stress on bladder function and the potential for PACAP(6-38), a PACAP antagonist, to recover normal function. Mice went through a repeated variate stress regime followed by bladder tube implant and cystometrogram recording. Bladder, dorsal root ganglia (DRG), and spinal cord tissues were collected and immunostained for the presence of TRPV1, TRPV4, and PACAP expression. Chronic stress decreased inter-contraction interval (ICI) and bladder capacity while increasing bladder pressures. Both control and stressed male and female mice showed improvement following a 30-minute intravesical infusion of PACAP(6-38), with ICI and bladder capacity measures having the most consistent improvement across groups. PACAP and TRPV1 expression was upregulated in the bladder afferent pathway. These findings suggest that chronic stress can contribute to bladder dysfunction, and it seems to be mediated in part by upregulation of PACAP and TRPV channel activity. With further research, these factors may be valid molecular targets for therapy. As chronic stress may present alone or in combination with other conditions (IC/BPS, injury, etc.), it is critical to understand stress-related changes in order to reduce or eliminate their impact.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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