Two of the synaptic receptors involved in the regulation of micturition, P2X₃ receptor, which is operated by ATP, and vanilloid receptor 1 (VR1), which is operated by capsaicin, are regarded as newcomers. To investigate the possibility that these receptors act as therapeutic targets for treatment of an overactive bladder, we investigated their distribution and reciprocal relationship. Eight-week-old Sprague Dawley rats were injected with retrograde nerve tracer within the bladder wall, and 15 rats were injected with 0.5% acetic acid inside the bladder. After a week, the animals were killed, and their dorsal root ganglia (DRG) at the levels of L6 and S1 were harvested. Immunohistochemistry or Western blot analysis of P2X₃ and VR1 were performed on the DRG. The DRG neurons with afferent fibers from the bladder had increased expression of VR1 and downregulated P2X₃ receptors. The P2X₃ receptor and VR1 seemed to account for the important parts of the hypersensitivity of the inflammatory bladder. We conclude that the simultaneous modulations of both P2X₃ receptor and VR1 may have a synergic effect on the treatment of overactive bladder and may produce greater response rates