Functional study of the bladder mechanosensitive afferent pathways

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We have established the measurement of single-unit afferent activities (SAAs) of the bladder mechanosensitive primary afferent nerve fibers in in vivo rats, and have investigated the effect of several drugs on these SAAs in this experimental set-up. The study demonstrated that L-arginine (an NO substrate), tadalafil and sildenafil (PDE5 inhibitors), and mirabegron (a β3-adrenoceptor (β3-AR) agonist), can inhibit both Aδ- and C- mechanosensitive afferent fiberst. Moreover, the activation of TRPV4 in the bladder, probably urothelium, facilitated the micturition reflex by P2X-purinoceptor-mediated activation of the mechanosensitive capsaicin-insensitive C-fibers. In addition, L-arginine and tadalafil can inhibit the activation of both fibers induced by intravesical acrolein, a metabolite of cyclophosphamide. We further investigated the relationship between the SAAs and bladder microcontractions, which have been recognized of myogenic origin. The results showed that mirabegron inhibited both bladder microcontractions and Aδ-fiber afferent activity, suggesting that the microcontractions may be linked to the mechanosensitive afferent activities of Aδ-fibers. In another study, we have established the measurement of SAAs synchronized with rhythmic bladder contractions. We found that mechanosensitive afferent activities of both Aδ- and C- fibers of the rat bladder are capable of being responsive to both stretch and contractile stimuli, and. that L-arginine and mirabegron inhibit the activation of mechanosensitive afferent nerves induced by bladder contractions.