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Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin\u2010induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin\u2010induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti\u2010inflammatory effect of testosterone while<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin\u2010induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti\u2010inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.<\/jats:p>","DOI":"10.1016\/j.ejpain.2011.06.007","type":"journal-article","created":{"date-parts":[[2011,7,9]],"date-time":"2011-07-09T09:40:17Z","timestamp":1310204417000},"page":"204-216","source":"Crossref","is-referenced-by-count":39,"title":["Effect of gonadal steroid hormones on formalin\u2010induced temporomandibular joint inflammation"],"prefix":"10.1002","volume":"16","author":[{"given":"K.E.","family":"Torres\u2010Ch\u00e1vez","sequence":"first","affiliation":[{"name":"Department of Physiology Piracicaba Dental School, State University of Campinas \u2013 UNICAMP Piracicaba S\u00e3o Paulo 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