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Estrogen has been reported to affect pain perception, although the underlying mechanisms remain unclear.In this investigation, pain behavior testing, patch clamp recording and immunohistochemistry were used on rats and transgenic mice to determine which estrogen receptors and the related signaling pathway are involved in the rapid modulation of estrogen on P2X3 receptor-mediated events.The results showed that 17(β)-estradiol rapidly inhibited pain induced by a,(β)-methylene ATP (a,(β)-me-ATP), a P2X1 and P2X3 receptor agonist in ovariectomized rats and normal rats in diestrus.