Editorial Comment to Pathophysiology of urinary incontinence in murine models


Among incontinent women, estimates are that 50% suffer from a type of stress urinary incontinence (SUI).[1] Only a few drugs have a beneficial effect on the treatment of SUI. Because the prevalence of SUI is greatest among the elderly, it is important that therapeutic risks are taken into consideration for older patients. Surgical intervention is not without risks, and SUI is not a life-threatening ailment.

Indeed, the pathophysiology of SUI has been well summarized in a recent review.[2] In the current literature, there are some interesting points about sex difference in urethral closure mechanisms and urethral compensatory mechanisms to maintain urinary continence after vaginal delivery.

There is no ideal model that truly mimics the likely multifactorial aspect of the pathophysiology of SUI. What are the limitations of the SUI murine model? The first one is a behavior difference between rats and humans. Rats walk with four legs, whereas humans walk with two legs in a standing position. The second one is the duration of urethral functional damage after injury.

Even with such limitations, a SUI animal model could be useful for preclinical testing of pharmacological agents and understanding the pathophysiology of SUI. Recently, Kadekawa et al. reported that propiverine treatment that increases plasma catecholamine levels could contribute to improvement of SUI conditions by increasing urethral resistance using a rat SUI model.[3] This is a new mechanism of SUI drug for urethral function, shown by an animal model.

Clinically, the symptoms of SUI often do not appear until a few years after the last delivery. Animal studies could be useful for testing the effect of vaginal childbirth. However, SUI animal models have been criticized because of the relatively short durability. In this review, Koike et al. reported that urethral smooth muscle activity might be enhanced by switching from nitric oxide-mediated relaxation to the α1-AR and MR-mediated contractile responses 4 weeks after pudendal nerve injury to compensate for the deficient striated muscle function.[4] This is quite an interesting point, and we can glimpse one side of the recovery mechanism after vaginal childbirth. However, such a recovery system has multiple components, so we require an integrated understanding of the urethral functional recovery mechanism. Further studies are required to clarify components. I hope that clarification of the pathophysiology of SUI might bring hope to the SUI patients.

Conflict of interest

None declared.