We examined nociceptive responses to mechanical stimulation in mice of both sexes lacking the
estrogen receptor alpha or beta and in respective wild types under normal conditions, after
inflammation of a hindpaw or
peripheral nerve injury. In normal wild-type mice, females had significantly lower paw withdrawal threshold than males. There was no significant difference between wild-type mice and knock-outs of either
estrogen receptor alpha or beta in mechanical response threshold in male mice. However, significantly elevated response threshold was observed in both knock-out female mice, which eliminated sex differences in nociception. After
carrageenan-induced
inflammation of a hindpaw, all wild-type and knock-out mice exhibited similar local
edema with no difference between the sexes. Wild-type mice developed
hypersensitivity (
allodynia) to mechanical stimulation, which was more profound in the females than in males. Again, such sex difference was not observed in the knock-outs of either
estrogen receptor. Photochemically induced partial sciatic nerve injury caused similar persistent mechanical
hypersensitivity in the wild types and both
estrogen receptor knock-outs with no difference between the sexes. These results suggest that the sex difference in basal mechanical pain threshold and inflammatory
hypersensitivity is eliminated in mice lacking either the
estrogen alpha receptors or beta receptors. However, these receptors do not seem to be directly involved in mediating
pain sensitivity in general or in the development of
neuropathic pain. It is unclear whether the elimination of sex differences observed in the knock-outs reflects an ongoing effect of
estrogen acting through its receptors in females or the developmental changes that predominantly affect females.