Intravesical Infusion of Budesonide Foam Improves Symptoms in a Bladder Pain Syndrome/Interstitial Cystitis Rat Model
- 1 Southern Knights’ Laboratory, Okinawa, Japan
- 2 Southern Knights’ Laboratory, Okinawa, Japan
- 3 Southern Knights’ Laboratory, Okinawa, Japan
- 4 Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
- 5 Southern Knights’ Laboratory, Okinawa, Japan
- 6 Department of Cytopathology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
- 7 Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
Abstract
Purpose: Since intravesically administered steroid therapy may treat bladder pain syndrome/interstitial cystitis (BPS/IC) with fewer side effects than the current treatment of orally administered steroids, we investigated whether the intravesical infusion of budesonide foam can effectively treat BPS/IC symptoms in a rat model of tranilast-induced BPS/IC. Methods: There were 6 rat treatment groups (n = 8 per group): control + single or daily saline infusion, tranilast + single or daily saline infusion, and tranilast + single or daily budesonide infusion. All groups except for the controls were fed a tranilast supplemented diet for 5 weeks. Budesonide and saline were infused intravesically. After the BPS/IC rat model underwent single infusion treatments, we measured the paw pain threshold using the von Frey test and continuous cystometry was taken. After two weeks of daily intravesical infusions, we measured locomotor activity and serum cortisol levels; harvested bladders underwent histological analysis. Results: Both pain threshold and locomotor activity were significantly lower in the saline-infused groups receiving the tranilast diet, but there were no differences between the budesonide-infused groups and the controls. The interval between bladder contractions was significantly shorter in the tranilast group than the control or tranilast + budesonide infusion groups. The serum cortisol levels did not change. Hematoxylin-Eosin stainings of the bladder showed thickening of the bladder muscle layer and mucosal edema in the tranilast group, while the tranilast + budesonide infusion group showed only mild changes. Conclusion: Intravesical infusion of budesonide effectively treated BPS/IC symptoms in a rat model of BPS/IC.
- van de Merwe, J.P., Nordling, J., Bouchelouche, P., Bouchelouche, K., Cervigni, M., Daha, L.K., Elneil, S., Fall, M., Hohlbrugger, G., Irwin, P., Mortensen, S., van Ophoven, A., Osborne, J.L., Peeker, R., Richter, B., Riedl, C., Sairanen, J., Tinzl, M. and Wyndaele, J.-J. (2008) Diagnostic Criteria, Classification, and Nomenclature for Painful Bladder Syndrome/Interstitial Cystitis: An ESSIC Proposal. European Urology, 53, 60-67. https://doi.org/10.1016/j.eururo.2007.09.019
- Fall, M., Baranowski, A.P., Elneil, S., Engeler, D., Hughes, J., Messelink, E.J., Oberpenning, F., de C Williams, A.C. and European Association of Urology (2010) EAU Guidelines on Chronic Pelvic Pain. European Urology, 57, 35-48. https://doi.org/10.1016/j.eururo.2009.08.020
- Ochs, R.L., Stein, T.W., Peebles, C.L., Gittes, R.F. and Tan, E.M. (1994) Autoantibodies in Interstitial Cystitis. The Journal of Urology, 151, 587-592. https://doi.org/10.1016/S0022-5347(17)35023-1
- Sugaya, K., Nishijima, S., Yamada, T., Miyazato, M., Hatano, T. and Ogawa, Y. (2002) Molecular Analysis of Adrenergic Receptor Genes and Interleukin-4/Interleukin-4 Receptor Genes in Patients with Interstitial Cystitis. The Journal of Urology, 168, 2668-2671. https://doi.org/10.1016/S0022-5347(05)64241-3
- Nishida, T., Kusakai, Y. and Ogoshi, R. (1985) Four Cases of Cystitis Induced by the Anti-Allergic Drug Tranilast. Hinyokika Kiyo, 31, 1813-1817.
- Okada, H., Minayoshi, K. and Goto, A. (1992) Two Cases of Eosinophilic Cystitis Induced by Tranilast. The Journal of Urology, 147, 1366-1368. https://doi.org/10.1016/S0022-5347(17)37569-9
- Sakai, N., Yamada, T. and Murayama, T. (1998) Eosinophilic Cystitis Induced by Tranilast: A Case Report. Hinyokika Kiyo, 44, 45-47.
- Suzawa, H., Kikuchi, S., Arai, N. and Koda, A. (1992) The Mechanism Involved in the Inhibitory Action of Tranilast on Collagen Biosynthesis of Keloid Fibroblasts. The Japanese Journal of Pharmacology, 60, 91-96. https://doi.org/10.1254/jjp.60.91
- Yamamoto, M., Yamauchi, T., Okano, K., Takahashi, M., Watabe, S. and Yamamoto, Y. (2009) Tranilast, an Anti-Allergic Drug, Down-Regulates the Growth of Cultured Neurofibroma Cells Derived from Neurofibromatosis Type 1. The Tohoku Journal of Experimental Medicine, 217, 193-201. https://doi.org/10.1620/tjem.217.193
- Nishijima, S., Sugaya, K., Kadekawa, K., Ashitomi, K., Ueda, T. and Yamamoto, H. (2013) High-Dose Tranilast Administration to Rats Creates Interstitial Cystitis-Like Symptoms with Increased Vascular Permeability. Life Sciences, 93, 897-903. https://doi.org/10.1016/j.lfs.2013.10.010