Decrease in bladder overactivity with REN1820 in rats with cyclophosphamide induced cystitis.
OBJECTIVE
Studies suggest that nerve growth factor (NGF) contributes to bladder overactivity stemming from bladder inflammation. Studies were performed to determine the NGF dependence of cyclophosphamide (CYP) induced changes in bladder function using the recombinant NGF sequestering protein REN1820.


METHODS
Urodynamic testing and behavioral observations were made in female rats treated with CYP (4 or 48 hours) and REN1820 or vehicle.


RESULTS
Rats examined 4 or 48 hours after CYP treatment plus REN1820 showed significantly fewer nonvoiding contractions with smaller amplitude (p </=0.01). Rats examined 48 hours after CYP treatment plus REN1820 showed decreased voiding frequency (p </=0.01). No changes in filling, threshold or micturition pressure were observed with REN1820 treatment. Rats treated with CYP plus REN1820 showed greater mobility and normal resting postures compared with rats treated with CYP plus vehicle.


CONCLUSIONS
These studies demonstrate that the use of the NGF sequestering protein REN1820 in rats with CYP induced cystitis decreases bladder overactivity. This is characterized by 1) a decrease in the number and amplitude of nonvoiding contractions and 2) decreased voiding frequency. Rats treated with REN1820 showed greater mobility and normal resting postures, which may reflect improved overall health or well-being. REN1820 may prove to be a novel therapeutic in individuals with the chronic inflammatory bladder syndrome interstitial cystitis.
Hu
Vivian Y
VY
Departments of Neurology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Zvara
Peter
P
Dattilio
Abbey
A
Redman
Travis L
TL
Allen
Shelley J
SJ
Dawbarn
David
D
Stroemer
R Paul
RP
Vizzard
Margaret A
MA
D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000627:therapeutic use*; D011994:Recombinant Proteins; D013997:Time Factors
D011994:Recombinant Proteins; C498075:tyrosine receptor kinase A Ig2; D003520:Cyclophosphamide; D020917:Receptor, trkA