The potential of non-adrenergic, non-cholinergic targets in the treatment of interstitial cystitis/painful bladder syndrome.

Regulation of bladder function involves both divisions of the autonomic nervous system. However, in addition to the classical autonomic transmitters, noradrenaline and acetylcholine, other autonomic transmitters and other signalling components play important roles in physiology and pathophysiology of the lower urinary tract. Several substances of neuronal non-adrenergic, non-cholinergic (NANC) systems have already proven to considerably influence functional responses in the inflamed urinary bladder. Interstitial cystitis (IC) or painful bladder syndrome (PBS) is a chronic inflammatory bladder disease, characterized by urinary frequency, urgency and pelvic pain. IC/PBS is difficult to diagnose, especially because the etiology of the condition is largely unknown. Despite the unclear nature of the cause and manifestation of IC/PBS, it has been shown that the disease involves a significant NANC component. Here, we review the possible roles of ATP, adenosine, nitric oxide, vasoactive intestinal polypeptide, substance P, and pituitary adenylate cyclase-activating peptide in the contribution to IC/PBS development and manifestation of IC/PBS symptoms.