Bladder dysfunction and altered somatic sensitivity in PACAP-/- mice.
OBJECTIVE
PACAP and receptors are expressed in micturition pathways. Studies show that PACAP has a role in detrusor smooth muscle contraction to facilitate adenosine triphosphate release from urothelium and PACAP antagonism decreases cyclophosphamide induced bladder hyperreflexia.


METHODS
PACAP contributions to micturition and somatic sensation were studied in PACAP knockout (PACAP(-/-)), litter mate heterozygote (PACAP(+/-)) and WT mice by conscious cystometry with continuous intravesical saline or acetic acid (0.5%) instillation, urination patterns, somatic sensitivity testing of hind paw and pelvic regions with calibrated von Frey filaments, and morphological bladder assessments.


RESULTS
PACAP(-/-) mice had an increased bladder mass with fewer but larger urine spots. In PACAP(-/-) mice the lamina propria and detrusor smooth muscle were significantly thicker but the urothelium was unchanged. PACAP(-/-) mice had increased bladder capacity, voided volume and intercontraction interval with significantly increased detrusor contraction duration and large residual volume. WT mice responded to acetic acid (0.5%) with a decrease in voided volume and intercontraction interval but PACAP(+/-) and PACAP(-/-) mice did not respond. PACAP(-/-) mice were less responsive to somatic stimulation. PACAP(+/-) mice also had bladder dysfunction, and somatic and visceral sensory abnormalities but to a lesser degree.


CONCLUSIONS
PACAP gene disruption contributes to changes in bladder morphology and function, and somatic and visceral hypoalgesia.
May
Victor
V
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Vizzard
Margaret A
MA
D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000502:physiology*; D020886:Somatosensory Disorders / Q000209:etiology* / Q000235:genetics; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide