Previous studies by us [48,49] and others [50] have demonstrated that during cystitis the ERK5 and CREB are activated in bladder afferent neurons and intrathecal application of PD98059, an inhibitor that prevents both ERK1/2 and ERK5 activities [51], significantly decreases micturition frequency in inflamed animals but has no effect on bladder reflex contractions of non-inflamed bladder. Here, CREB1 is linked to cystitis.