下部尿路機能障害に対する新規治療標的としてのTRPM8チャネルの可能性

抄録

Storage symptoms of overactive bladder, benign prostatic hyperplasia, and interstitial cystitis/bladder pain syndrome are commonly related to sensory function (bladder hypersensitivity).

In the lower urinary tract, transient receptor potential (TRP) channels are primarily involved in physiological function, especially in cellular sensors responding to chemical and physical stimuli. Among TRP channels, TRP melastatin 8 (TRPM8) channels, responding to cold temperature and/or chemical agents, such as menthol or icilin, are mainly expressed in the nerve endings of the primary afferent neurons and in the cell bodies of dorsal root ganglia innervating the urinary bladder (via Aδ- and C-fibers); this suggests that TRPM8 channels primarily contribute to bladder sensory (afferent) function and may also contribute to the pathophysiology of bladder hypersensitivity. Indeed, it has been reported in a pharmacological investigation using rodents that TRPM8 channels contribute to the pathophysiological bladder afferent hypersensitivity of mechanosensitive C-fibers. Similar findings have also been reported in humans. Therefore, a TRPM8 antagonist would be a promising therapeutic target for bladder hypersensitive disorders, including urinary urgency or nociceptive pain.

In this workshop, I show the functional role of the TRPM8 channel in the lower urinary tract and the potential of its antagonist for the treatment of bladder hypersensitive disorders.