We show (1) that sprouting of afferent neurons is a hallmark of CYP-induced cystitis in rats and mice, without recruitment of new fibres, (2) that the expression of TRPC1 and TRPC4 is increased in bladder-innervating sensory neurons of CYP-treated animals, (3) that double knock-out mice (Trpc1/c4−/−) fail to develop increased innervation of the bladder wall following CYP-treatment, and (4) finally that CYP-induced bladder overactivity is less pronounced in these Trpc1/c4−/− mice. The gene discussed is C4A; the disease is overactive bladder.