Effect of gonadal steroid hormones on formalin‐induced temporomandibular joint inflammation

Abstract

We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced 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-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 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-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced 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-inflammatory 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.

Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic–pituitary–adrenal axis activity

“…It is well established that estrogen displays analgesic properties in animal models of inflammatory pain and that estrogen antiinflammatory and antinociceptive effects have been postulated to be in part mediated through down regulation of inflammatory modulators [23,47–49]. Here we analyzed the cytokine profile during estradiol administration before and following formalin injection and observed that estrogen directly regulates pro- and antiinflammatory cytokine levels in vivo .…”

P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis

“…The optical density was read at 450 nm using an Asys UVM340. After that, the results were calculated by comparing the optical density of rat’s knee joint synovial lavage fluid supernatant with a standard curve of neutrophil (>95% purity), as previously described [43]. The results were presented as number of neutrophils × 10 4 /knee.…”

The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia

“…The myeloperoxidase kinetic-colorimetric assay was used, as previously described (Torres-Chavez et al, 2012). Three hours after injection, the tissue of the plantar surface of the hind paw was dissected into a standard sized sample, weighed, quickly frozen by liquid isopentane in dry ice and stored at À70 C. In the assay procedure, each sample was homogenized in 500 ml of buffer 1 (0.1 M NaCl, 0.02 M NaPO 4 , 1.015 M Na EDTA, pH 4.7) followed by centrifugation at 3000 rpm for 15 min.…”

“…The optical density was read at 450 nm using an Anthos 2020. Results were calculated by comparing the optical density of hind paw tissue supernatant with a standard curve of neutrophil (>95% purity) obtained as previously described (Torres-Chavez et al, 2012). The results were presented as number of neutrophils Â10 6 /mg tissue.…”