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Sources of Funding: PFD Research Foundation and ICA IC/PBS Research Grant._x000D_ Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010.

Introduction

Stressful events occurring in childhood seems to have a role BPS/IC development in adulthood. We investigate if the maternal deprivation model (MDM) is an appropriate animal model to study such link, by characterizing bladder changes.

Methods

MDM was induced from P2 to P15, for 1h, on female C57BL/6. Pups were separated from mother and from littermates. Non separated female pups were used as controls. _x000D_ At P156, mechanical pain threshold were analysed at P156, by applying Von Frey filaments at the abdomen. At P157, animals were anaesthetised and cystometry was performed. Afterwards, bladders were harvested, fixed, sectioned and stained with HE (to analyse urothelium integrity) and with Toluidine blue (to analysed mast cell). _x000D_ The MDM was repeated on female TRPV1 knockout (KO) mice to investigate the role of TRPV1 nociceptors in this model.

Results

WT lower abdominal pain threshold was 0.08±0.01g. MDM WT decreased their threshold to 0.02±0.01 (P=0.0002). TRPV1 KO and MDM TRPV1 KO mice had a similar lower abdominal pain threshold (0.13±0.18g and 0.28±0.14g, respectively; P=0.2). _x000D_ WT had 0.48±0.15 bladder contractions/minute. MDM WT bladder frequency increased to 1.05±0.35 bladder contractions/minute (P=0.04). TRPV1 KO and MDM TRPV1 KO bladder frequency was 0.50±0.12 bladder contractions/minute and 0.50±0.08 bladder contractions/minute, respectively._x000D_ The bladder of WT and TRPV1 KO had normal urothelium (0% of disrupted urothelium). MDM WT had 7±7% of disrupted urothelium. MDM TRPV1 KO urothelium was similar to the one observed in WT female (0% of disrupted urothelium)._x000D_ Mastocytosis was not observed in any of MDM animals.

Conclusions

MDM mimics bladder dysfunction observed in BPS/IC, as MDM WT felt pain, had bladder hyperactivity and mild urothelial disruption. TRPV1-expressing fibres seem to have a role in the development of bladder changes has MDM TRPV1 KO mice did not present the changes observed in MDM WT. Therefore, we conclude that MDM model may be useful to investigate the consequences of childhood stressful events, in particular mechanism leading to the development of chronic bladder pain in adulthood.

Funding

PFD Research Foundation and ICA IC/PBS Research Grant._x000D_ Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010.