In addition, we recently showed that levels of released HMGB1 are correlated with PAR4-induced bladder pain [10] and HMGB1 plays a pivotal role in mediating pain in this model since systemic treatment with glycyrrhizin (HMGB1 antagonist) prevents acute PAR4-induced bladder pain [3] while systemic treatment with ethyl pyruvate (to prevent HMGB1 release) decreased established PAR4-induced bladder pain [10]. Here, HMGB1 is linked to carcinoma.