Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats

Abstract

We investigated the function and expression pattern of the transient receptor potential melastatin-8 (TRPM8) in urinary bladder afferent neurons from control and bladder outlet obstruction (BOO) rats. BOO was produced and, after six weeks, the effects of intravesical infusion of menthol, the agonist of TRPM8, were investigated using unanesthetized cystometry. The intravesical infusion of menthol produced an increase in the micturition pressure in both sham surgery and BOO rats. In BOO rats, increased basal and threshold pressure and a decreased micturition interval were observed. Next, the population of TRPM8-positive and the co-expression proportion of TRPM8 with neurochemical markers (NF200 or TRPV1) in the bladder afferent neurons were each compared between the control and BOO rats using retrograde tracing and immunohistochemistry. The population of TRPM8-immunoreactive bladder afferent neurons was larger in BOO rats (3.28±0.43%) than in the control rats (1.33±0.18%). However, there were no statistical differences between the control and BOO rats in the co-expression proportion of neither TRPM8-NF200 (84.1±4.3% vs 79.7±2.7%, p=0.41) nor TRPM8-TRPV1 (33.3±3.6% vs 40.8±2.6%, p=0.08) in the bladder afferent neurons. The present results suggest that the neuronal input through TRPM8-positive bladder afferent neurons are augmented after BOO, however, the neurochemical phenotype of the up-regulated TRPM8-positive bladder afferent neurons is not changed after BOO.