Neonatal cystitis-induced colonic hypersensitivity in adult rats: a model of viscero-visceral convergence


Address for Correspondence
Adrian Miranda, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Tel: +414 456 4011; fax: +414 456 6361;


Background  The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms.

Methods  Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days [(postnatal (PN) days 14–16)]. The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissues. CRD- or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-d-aspartic acid (NMDA)-NR1 subunit in the lumbo-sacral (L6-S1) spinal cord was examined using Western blot.

Key Results  The VMR to CRD (≥10 mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan-treated rats was significantly higher than the saline-treated control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (> 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared with saline-treated rats (< 0.05).

Conclusions & Inferences  Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does result in overexpression of spinal NR1 subunit in adult rats.