Ablation of estrogen receptor alpha or beta eliminates sex differences in mechanical pain threshold in normal and inflamed mice.
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.
Li
Lili
L
Section of Clinical Neurophysiology, Department of Clinical Neuroscience, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
Fan
Xiaotang
X
Warner
Margaret
M
Xu
Xiao-Jun
XJ
Gustafsson
Jan-Ake
JA
Wiesenfeld-Hallin
Zsuzsanna
Z
D000818:Animals; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D017288:Pain Threshold / Q000502:physiology*; D012737:Sex Factors; D014110:Touch
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta