**3.2 Telocytes in bladder diseases**

The micturition reflex is the result of a complex integration among involuntary and voluntary nervous mechanisms. Several pathological conditions of the low urinary tract compromise this function causing detrusor dysfunctionality. The most frequent is the idiopathic detrusor overactivity, the neurogenic detrusor overactivity (NDO), the bladder pain syndrome/interstitial cystitis, and the partial bladder outlet obstruction. All these diseases are characterized functionally by excessive sensitivity of the detrusor/bladder to filling [58], and histologically by an intense inflammation especially in the lamina propria [35, 38, 59, 60]. Since it is well known that TCs and myofibroblasts produce cytokines and other molecules able to recruit immune cells and express receptors for the cytokines released by the immune cells, both cell types likely intervene in the inflammation intensity, quality, and duration. Furthermore, in the presence of detrusor hyperactivity, both ULP-TC and myofibroblasts showed an increase of the Cx43 protein labeling that was interpreted as an augmentation of the gap junctions and signs of cellular activation (clear nuclei and larger bodies) [35, 38, 59, 61]. Additionally, the TCs expressing both PDGFRα and α-SMA were significantly increased in comparison with controls suggesting a shift toward a myofibroblast phenotype [35, 38]. All these cell changes were considered signs of adaptability because, despite the presence of inflammation, the 3D cell network was preserved [38, 59]. However, this integrity not necessarily means adequate functionality of the sensory system made by the urothelium and the ULP; in fact, the higher thickness of the ULP, due to the intense cell infiltrate and edema, forcing the net meshes to enlarge, could cause an increase in the distances among the cells, between them and the nerve endings, and between all of them and the urothelium, likely affecting the sensitivity to volume changes and the capability of responding to the molecules released by the nerve terminals and by the urothelium. Finally, because the ULP thickening was uneven alongside the organ [35, 38, 60], foci of hypersensitivity could alternate to others less responding, further prejudicing the correct integration of the afferent stimuli [57]. Finally, it was reported that the TCs forming the monolayer underlying the urothelium did not show any significant changes in hyperactive bladders. These data were explained as follow: the location of these TCs could spare them from the damages caused by the cell infiltrate. Further, if these TCs are engaged in cell proliferation and differentiation of the overlying epithelium, the absence of epithelial cell death signs in NDO might account for their sparing.
