Enhanced expression of mast cell growth factor and mast cell activation in the bladder following the resolution of trinitrobenzenesulfonic acid (TNBS) colitis in female rats.
OBJECTIVE
Chronic pelvic pain disorders often overlap. We have shown that acute colonic irritation can produce acute irritative micturition patterns and acutely sensitize bladder afferent responses to mechanical and chemical stimuli. We hypothesize that with time, colonic irritation can lead to neurogenic changes in the bladder and the development of chronic bladder sensitization.


METHODS
Micturition patterns were measured in rats 60-90 days after the induction of trinitrobenzenesulfonic acid (TNBS) colitis in the resolution phase of this model. Total and activated mast cells (MCs) were quantified in the bladder, while mRNA levels of stem cell factor (SCF; a.k.a. MC growth factor) and nerve growth factor (NGF; a MC and nociceptive C-fiber stimulator) were quantified in the bladder and L6-S1 dorsal root ganglia (DRG).


RESULTS
Following intra-rectal TNBS, voiding volume was reduced (P < 0.005), while voiding frequency was increased (P < 0.05), both by approximately 50%. Furthermore, both the percentage and density of activated bladder MCs were significantly elevated (P < 0.05), although total MC counts were not statistically increased. At the molecular level, urinary bladder SCF expression increased twofold (P < 0.005), as did NGF (P < 0.01), while L6-S1 DRG levels were not significantly elevated.


CONCLUSIONS
Chronic cystitis in the rat as evidenced by changes in micturition patterns and the recruitment of activated MCs can occur during the resolution phase of TNBS colitis. These changes, of which MCs may play an important role, appear to be maintained over time and may occur via stimulation of convergent pelvic afferent input resulting in the upregulation of neurotrophic factors in the target organ.
Liang
Ruomei
R
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Ustinova
Elena E
EE
Patnam
Radhika
R
Fraser
Matthew O
MO
Gutkin
Dmitriy W
DW
Pezzone
Michael A
MA
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000235:genetics*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D014554:Urination / Q000502:physiology*
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D019089:Stem Cell Factor; D014302:Trinitrobenzenesulfonic Acid