['Nicotinic afferent pathways may be involved in the regulation of bladder inflammation. Based on that hypothesis we investigated the role of nicotinic signaling in a comparative analysis of 2 models of experimental bladder inflammation using protamine sulfate and cyclophosphamide.', 'Protamine sulfate and cyclophosphamide were used to induce acute bladder inflammation. Nicotinic agonists and antagonists were given concomitant to the bladder inflammatory agents. Changes in bladder inflammation were measured histologically by a pathologist and through the expression of inflammatory genes.', 'Histologically cyclophosphamide induced more inflammatory changes than protamine sulfate during acute bladder inflammation. Antagonizing nicotinic signaling with mecamylamine induced further inflammatory changes on histology when used with cyclophosphamide but not with protamine sulfate. However, antagonizing nicotinic signaling in combination with protamine sulfate induced greater increases in mRNA expression of the inflammatory cytokine interleukin-6 compared to cyclophosphamide and mecamylamine combination treatments. The activation of nicotinic signaling attenuated acute bladder inflammation by protamine sulfate and cyclophosphamide independently through the down-regulation of increased interleukin-6 expression.'] Does nicotinic signaling ameliorate acute bladder inflammation induced by protamine sulfate or cyclophosphamide?