1. Academic Validation
  2. Intravesical PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

Intravesical PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

  • J Mol Neurosci. 2016 Jun;59(2):290-9. doi: 10.1007/s12031-016-0764-1.
Beatrice M Girard 1 Susan E Malley 1 Morgan M Mathews 1 Victor May 1 Margaret A Vizzard 2
Affiliations

Affiliations

  • 1 Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA.
  • 2 Department of Neurological Sciences, College of Medicine, University of Vermont, D405A Given Research Building, Burlington, VT, 05405, USA. margaret.vizzard@uvm.edu.
Abstract

Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6-38) (300 nM), significantly (p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6-38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6-38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6-38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice.

Keywords

Bladder pain syndrome; Cystometry; Interstitial cystitis; Neuropeptides; Pelvic pain; Urinary bladder.

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