Visceral Organ Cross‐Sensitization in a Rodent Model of Early Life Stress

Abstract

INTRODUCTION AND OBJECTIVEBladder pain syndrome (BPS) and irritable bowel syndrome (IBS) exhibit a high comorbidity, show a female predominance, and patients often report a history of early life stress (ELS). However, whether ELS serves as a risk factor for visceral organ cross‐sensitization remains to be determined. Our previous work suggests that multi‐organ visceral hypersensitivity results from visceral organ crosstalk. In this study, we test the novel hypothesis that ELS induces chronic visceral pain in adults through bladder‐colon crosstalk.METHODSNeonatal female Long Evans rats were exposed to an odor attachment learning model of ELS produced by classical conditioning. On postnatal (PN) days 8 to 12 neonatal female rats (n=27) were separated into: Group 1: odor with an unpaired shock [Unpredictable ELS], Group 2: odor only. In adulthood (PN 90) dilute protamine sulfate (PS) (1mg/ml) was infused into the bladder via intravesical infusion. Colon sensitivity was assessed 24 hr. post PS in freely moving animals as a visceromotor response (VMR) to graded pressures (0–60mmHg) of isobaric colorectal distension and quantified as the number of abdominal contractions over 10 min. Rats receiving no PS infusion served as controls.RESULTSIn adults PS infusion into the bladder significantly increased colonic sensitivity in all groups (VMR at 60mmHg: Odor Only=21.4±1.7 (n=5) vs Odor Only plus PS=36.0±1.8 (n=10) [p<0.0001], Unpredictable ELS=38.7±3.6 (n=6) vs Unpredictable ELS plus PS=52.7±1.7 (n=6) [p<0.0001] abdominal contractions). The crosstalk‐induced increase in colonic hypersensitivity was similar between the odor only and unpredictable ELS groups (ΔVMR at 60mmHg (plus PS – no PS): Odor Only=14.6±1.7 vs Unpredictable ELS=14.0±3.6 [p=0.90]).SUMMARY & CONCLUSIONSOur data revealed that in adulthood intravesical infusion of PS into the bladder in female rats previously exposed to ELS as neonates induces colonic hyperalgesia, however the magnitude of the PS‐induced colonic hyperalgesia did not differ between groups. These findings, in a rodent model, suggest that unpredictable ELS does not augment acute visceral organ cross sensitization in adulthood.Support or Funding InformationIn‐house funding from the Greenwood‐Van Meerveld lab was used to support this project.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.