Furthermore, our findings that disulfide HMGB1 mediates bladder pain in a model with no overt bladder inflammation extend the findings of Tanaka et al [5] who found that systemic HMGB1 antagonists could prevent bladder pain after chemical (cyclophosphamide) injury of the bladder but did not affect inflammatory changes in this chemical cystitis model. This evidence concerns the gene HMGB1 and cystitis.