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Advisory Committee Chair

Meredith T Robbins

Advisory Committee Members

Franklin R Amthor

Edwin C Cook

Timothy J Ness

Robert E Sorge

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Disorders in which pain originates from the urinary bladder such as interstitial cystitis (IC) are steadily increasing in prevalence. A common finding among patients with IC is the comorbidity with stress or anxiety disorders. In rats, footshock stress alone is sufficient to elicit bladder hypersensitivity. Serotonin (5-hydroxytryptamine; 5-HT) has been established as a mediator in anxiety and pain separately, but little is known about the role of 5-HT in stress-induced visceral hypersensitivity. The current set of studies addresses three main concerns: (1) the impact of spinal 5-HT1A and 5-HT3 receptor blockade with WAY-100635 (10 µg) and ondansetron (10 µg), respectively, on visceromotor reflex (VMR) responses to urinary bladder distension (UBD) of rats exposed to chronic footshock stress, (2) the impact of chronic footshock stress on spinal and cerebrospinal fluid 5-HT, 5-HIAA, and 5-HIAA/5-HT concentrations, and (3) the impact of spinal 5-HT3 receptor blockade with ondansetron (100 µg ) on dorsal horn neuronal responses to UBD. Experiments used to test these concerns utilized Lewis rats, a strain which has not been used in studies of stress-induced bladder hypersensitivity. A significant increase in abdominal EMG responses to UBD was observed in rats exposed to chronic footshock stress compared to sham stress. Intrathecal WAY-100635 or ondansetron had no significant effect on abdominal EMG responses to UBD in stressed or non-stressed rats. Chronic footshock stress did not significantly alter spinal or CSF concentrations of 5-HT, 5-HIAA, or 5-HIAA/5-HT. Spinal application of ondansetron did not significantly alter neuronal responses to UBD in stressed or non-stressed rats. In light of these findings, preliminary results demonstrate that spinal non-specific 5-HT receptor blockade with methysergide (30 µg) significantly augmented the VMR response to UBD. Therefore, these results indicate that 5-HT is involved in the facilitation of stress-induced bladder hypersensitivity, but this facilitation does not rely exclusively on activation of either spinal 5-HT1A or 5-HT3 receptors.

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