Rats with CYP-induced chronic cystitis were used as an IC model, and the main findings were that (1) Piezo2 channels are expressed on most of the bladder primary afferents; (2) CYP-induced cystitis is associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels; and (3) knockdown of Piezo2 expression in DRG neurons by intrathecal injection of Piezo anti-sense ODNs suppressed mechanical stimulation evoked referred bladder pain and bladder hyperactivity in CYP rats. Here, PIEZO2 is linked to cystitis.