Basic mechanisms of urgency: preclinical and clinical evidence.
BACKGROUND
Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood.


OBJECTIVE
To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies.


METHODS
Review of published reports.


RESULTS
The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present.


CONCLUSIONS
The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.
Michel
Martin C
MC
Department of Pharmacology and Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Chapple
Christopher R
CR
D000818:Animals; D006801:Humans; D009119:Muscle Contraction; D012677:Sensation; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy