Pd55-04 Tibial and Pudendal Neuromodulation of Spinal Neuron Activity Induced by Bladder Distention

Abstract

METHODS: Female C57BL/6 mice received intravesical PAR4 (100mM; 1 hr) 3 times every other day and abdominal mechanical hypersensitivity (50% mechanical threshold) was tested before first PAR4 injection (baseline) and at days 1, 2, 3, 4, 7 and 9. At the end of the experiment, micturition changes were measured and bladders were examined for histological changes. MIF antagonist (MIF098; 40 mg/kg; i.p.; bid) or HMGB1 inhibitor (glycyrrhizin; 50 mg/kg; i.p.; daily) were administered daily starting from day 2 until day 8 after first instillation.RESULTS: Repeated control peptide instillation did change abdominal mechanical hypersensitivity. There was a significant and persistent abdominal mechanical hypersensitivity starting from day 3 after first intravesical instillation in the PAR4-treated group that persisted until day 9 (5 days post-last instillation). Glycyrrhizin fully reversed while MIF098 partially reversed abdominal mechanical hypersensitivity in PAR4 treated mice (Fig. 1). The changes started on day 3 after first PAR4 instillation and analgesic effects lasted throughout rest of testing period. There were no significant micturition changes or histological changes.CONCLUSIONS: Repeated intravesical PAR4 instillation produced persistent bladder pain without overt bladder inflammation that mimics debilitating bladder pain in PBS/IC patients. MIF and its signaling downstream (HMGB1) are effective targets for bladder pain alleviation.