Therapeutic targets for overactive bladder other than smooth muscle

Abstract

Introduction: For a long time, our concepts of regulation of urinary bladder function in health and disease as well as of the target structures of therapeutics have focused on detrusor smooth muscle cells. However, other structures including urothelium, afferent nerves and bladder blood vessels may also be important in pathophysiology and its treatment.

Areas covered: Based on a selective review of literature, we discuss the role of urothelium, afferent nerve fibers and bladder blood vessels in bladder pathophysiology and as targets for treatment.

Expert opinion: There is solid evidence now that multiple anatomical structures within the urinary bladder contribute to the regulation of its function and hence may be targets for established and emerging drugs. However, most previous studies have looked at the various target structures in isolation. In contrast, we propose that they should be seen as a network sensing and responding to alterations in the cellular environment or to xenobiotics. Studies are emerging in which the interaction of two of these structures is explored. Major advances in our understanding of bladder function are expected to result from studies integrating multiple such structures but these may be technically challenging and difficult to perform and interpret.

Keywords:

• afferent nerve
• bladder vasculature
• overactive bladder
• urothelium

Declaration of interest

MC Michel has received research support, consultant and/or lecturer honoraria in the OAB field from Allergan, AltheRX, Astellas, Bayer and Pfizer. Currently he is an employee of Boehringer Ingelheim. Research in his laboratory has been supported in part by grants from the Deutsche Forschungsgemeinschaft (MI 294/7-2) and Coordination Theme 1 (Health) of the European Community’s FP7, Grant agreement number HEALTH-F2-2008-223234. Y Igawa has received research support, consultant and/or lecturer honoraria in the OAB field from Astellas, Asahi-kasei, Kissei, Kyorin, Ono, Pfizer, RaQualia, Taiho, Daiichi-Sankyo and Nippon-Shinyaku. Research in his laboratory has been supported by a Grant-in-Aid for Scientific Research (Grant no. 40159588), from the Ministry of Education, Culture, Sport, Science and Technology of the Japanese government. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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