Urinary Bladder Function and Somatic Sensitivity in Vasoactive Intestinal Polypeptide (VIP)−/− Mice

Abstract

Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide widely distributed in neural pathways that regulate micturition. VIP is also an endogenous anti-inflammatory agent that has been suggested for the development of therapies for inflammatory disorders. In the present study, we examined urinary bladder function, hindpaw and pelvic sensitivity in VIP -/-and littermate wildtype controls. We demonstrated increased bladder mass and fewer but larger urine spots on filter paper in VIP -/-mice. Using cystometry in conscious, unrestrained mice, VIP -/-mice exhibited increased void volumes and shorter intercontraction intervals with continuous intravesical infusion of saline. No differences in transepithelial resistance or water permeability were demonstrated between VIP -/-and WT mice; however, an increase in urea permeability was demonstrated in VIP -/-mice. With the induction of bladder inflammation by acute administration of cyclophosphamide (CYP), an exaggerated or prolonged bladder hyperreflexia, hindpaw and pelvic sensitivity were demonstrated in VIP -/-mice. The changes in bladder hyperreflexia and somatic sensitivity in VIP -/-mice may reflect increased expression of neurotrophins and/or or proinflammatory cytokines in the urinary bladder. Thus, these changes may further regulate the neural control of micturition.

Involvement of JAK-STAT signaling/function after cyclophosphamide-induced bladder inflammation in female rats

“…3). The reduction in paw withdraw threshold was consistent with previous studies examining hind paw sensitivity after CYP-induced cystitis (23,48). Treatment with both concentrations of AG490 (5, 15 mg/kg) produced a similar and significant (P Յ 0.05) increase in paw withdraw threshold (Fig.…”

“…Four hours later, rats from all groups were tested for mechanical pain sensitivity using von Frey filament testing. Previous studies including those from this laboratory demonstrated hind paw sensitivity after CYP treatment (23,48). The 4-h time point after CYP treatment was selected for study in this experimental series because previous studies demonstrated increased peripheral mechanical sensitivity induced by CYP treatment at this time point with a return to baseline sensitivity 48 h after CYP treatment (48).…”

“…Behavioral testing was performed during the light cycle as previously described (48). Mechanical foot withdrawal threshold was determined using a series of von Frey filaments that produce forces ranging from 0.23 to 59.0 g. Rats were placed unrestrained in a plastic cage with a metal mesh floor and permitted to acclimate to this environment (30 min) before testing.…”

“…Previous studies in mice and rats demonstrate increased peripheral mechanical sensitivity after CYP-induced cystitis (23,48). To assess whether increased cytokine/cytokine signaling mediates some of the sensory changes associated with cystitis, hind paw mechanical sensitivity to von Frey filaments in CYP-treated and control (no inflammation) rats was tested in the presence of AG490 (5, 15 mg/kg ip).…”

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila

“…the ureter control the flow of urine into the terminal portion of the digestive tract (29,30) in a manner analogous to the VPAC2R + detrusor muscle of the mammalian bladder. Abnormal fluid regulation has also been described in mice lacking VIP or PACAP (40,42,43), so it will be of interest to establish if PDF signaling has related in vivo roles in flies. The presence of VIP/PACAP immunoreactivity in neural fibers of the lower urinary tract of mammals suggests a local, transmitter-like action on the excretory muscle receptors (12), and VIP is generally believed to act as a local neurotransmitter rather than as a circulating hormone (44,45).…”