Abstract: PD01-12
Sources of Funding: None

Introduction

The comorbidity between interstitial cystitis (IC) and irritable bowel syndrome (IBS) involves visceral organ cross sensitization. Previously we showed that infusion of protamine sulfate (PS) into the bladder increased bladder and colonic permeability and heightened colonic sensitivity within 24 hrs. Here we investigate the hypothesis that PS into the bladder causes persistent visceral organ hypersensitivity via activation of specific neuronal populations in the spinal cord.

Methods

Bladder hyperpermeability was induced in ovariectomized (OVX) female Sprague Dawley rats (n=44) through the transurethral infusion of PS (1 mg/ml); control rats received a sham infusion (n=13). Bladder and colonic permeability were assessed in vitro 1, 3, or 5 days post PS infusion via transepithelial electrical resistance (TEER). Bladder and colonic sensitivity were assessed in vivo 1, 3, or 5 days post PS infusion. Referred bladder hyperalgesia was measured using von Frey filaments (0.16-15g) applied to the suprapubic region and quantified via the frequency of withdrawal responses. Colonic sensitivity was assessed as the visceromotor behavioral response (VMR) to graded pressures (0-60mmHg) of isobaric colorectal distension (CRD) and quantified as the number of abdominal contractions. Neuronal activity in the spinal cord was assessed ex-vivo via immunofluorescence of phosphorylated extracellular signal-regulated kinase (pERK).

Results

PS infusion into the bladder caused no overt changes in bladder or colonic histology. However, PS significantly decreased bladder TEER (Day 5: 1628±39 vs. 2579±21 Ω/cm², P<0.001, n=5) and colonic TEER (Day 5: 135±8 vs. 224±17 Ω/cm², P<0.001, n=7) as compared to controls. Five days post bladder PS, rats exhibited bladder hyperalgesia (65±8 vs. 24±5 % withdrawal response at 15g, P<0.001, n=11) and colonic hypersensitivity (31±1.4 vs. 15±0.8 abdominal contractions at 60 mmHg, P<0.0001, n=11). PS treatment enhanced pERK expression within the dorsal horn of the spinal cord for up to 5 days (13±0.5 vs. 5±0.7 neurons/section, P<0.0001, n=12).

Conclusions

In response to a single infusion of PS into the bladder, our data highlights a persistent increase in i) permeability and pain sensitivity of the bladder and colon and ii) neuronal activity in the spinal cord. These findings advance our understanding of the mechanisms of visceral organ crosstalk and highlight the comorbidity between IC and IBS.

Funding

None