title: Urinary bladder hypersensitivity and dysfunction in female mice following early life and adult stress.
abstract: Early adverse events have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. Despite high clinical relevance and reports of stress-related symptom exacerbation, animal models investigating the contribution of early life stress to female urological pain are lacking. We examined the impact of neonatal maternal separation (NMS) on bladder sensitivity and visceral neuroimmune status both prior-to, and following, water avoidance stress (WAS) in adult female mice. The visceromotor response to urinary bladder distension was increased at baseline and 8d post-WAS in NMS mice, while colorectal sensitivity was transiently increased 1d post-WAS only in naïve mice. Bladder micturition rate and output, but not fecal output, were also significantly increased following WAS in NMS mice. Changes in gene expression involved in regulating the stress response system were observed at baseline and following WAS in NMS mice, and WAS reduced serum corticosterone levels. Cytokine and growth factor mRNA levels in the bladder, and to a lesser extent in the colon, were significantly impacted by NMS and WAS. Peripheral mRNA levels of stress-responsive receptors were differentially influenced by early life and adult stress in bladder, but not colon, of naïve and NMS mice. Histological evidence of mast cell degranulation was increased in NMS bladder, while protein levels of protease activated receptor 2 (PAR2) and transient receptor potential ankyrin 1 (TRPA1) were increased by WAS. Together, this study provides new insight into mechanisms contributing to stress associated symptom onset or exacerbation in patients exposed to early life stress.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Pierce
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Di Silvestro
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Eller
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Ryals
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3038, Kansas City, KS 66160, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Christianson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008426:Maternal Deprivation; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D012007:Rectum / Q000503:physiopathology; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000503:physiopathology*; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D003345:Corticosterone
keywords: Early life stress; Hippocampus; Hypothalamic-pituitary-adrenal axis; Interstitial cystitis; Maternal separation; Pain