The popular hypothesis of etiology in IC is many possible pathways cause bladder insult,especially damage to bladder epithelium, then induce the activation of c- fiber, mast cell activation, substance p, histamine release and immunogenic, allergic response. All of the response finally cause progressive bladder injury. In addition, There have non bladder comorbidities , such as chronic fatigue syndrome, fibromyalgia, IBS , and abuse history, anxiety, depression that would induce inadequate downward modulation of pain, cross talk of viscero visceral, viscero somatic, viscer muscular all results in autonomic dysfunction. When the time is long enough, all the condition will progress to so call central sensitization and up regulation of CNS. Then there will come to In the final stage of chronic neuropathic pain. The hypothesis tell us when we take care the IC patient not only the bladder , regional organs but also the central systems should be taken into consideration to have the better outcome.