Avaliação da influencia dos hormonios sexuais na nocicepção da articulação temporomandibular de ratos e estudo dos mecanismos envolvidos / The role of sex hormones in temporomandibular joint nociception and study of the mechanisms involved

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

The aim of this study was to evaluate the effect of sex hormones on temporomandibular joint (TMJ) nociception in rats and the possible mechanisms underlying their effect. The TMJ injection of 0.5% formalin induced nociception in intact females and gonadectomized males, but not in intact males, suggesting that the physiological level of testosterone protect males by decreasing their probability to develop TMJ pain. A higher dose of formalin (1.5%) induced a nociceptive behavior response significantly higher in female rats during diestrus phase of the estrous cycle than in those during proestrus phase and male rats. Since estradiol serum level was higher in proestrus than in diestrus females, this finding suggests that during low estradiol level of the estrous cycle the TMJ nociception is increased in female rats. Systemic administration of estradiol or progesterone in gonadectomized females and of testosterone in gonadectomized males significantly decreased 1.5% formalin-induced TMJ nociception. The role of sex and ovarian hormones in formalin and glutamate-induced TMJ nociception was virtually the same, showing that the antinociceptive effect of ovarian hormones was not exclusively related to the nociception induced by formalin. The similarity between clinical studies and the present results, obtained by using two different nociceptive agents, suggests that the TMJ behavior model may be useful and reliable to study the mechanisms underling the antinociceptive effect of sex hormones in the TMJ. Drug delivery to the medullary cerebrospinal fluid is also useful to study these mechanisms, however, the surgical procedure for implantation of the catheter used for drug delivery may affect the expression of the nociceptive behaviors related to orofacial nociception. Therefore, the technique for direct drug delivery to the medullary cerebrospinal fluid, without catheter implantation, will contribute for the study of the mechanisms underling the antinociceptive effect of sex hormones in the TMJ. The administration, though this technique, of the opioid receptor antagonist naloxone in the medullary region blocked the antinociceptive effect of estradiol, progesterone and testosterone. However, the co-administration of naloxone with formalin into the TMJ blocked the antinociceptive effect of progesterone and testosterone, but not of estradiol. These findings suggest that central opioid mechanisms mediate the antinociceptive effect of estradiol, progesterone and testosterone, while peripheral opioid mechanisms also mediated the antinociceptive effect of progesterone and testosterone. The local administration of estradiol, conjugated or not with the bovine serum albumin, significantly decreased formalin-induced TMJ nociception in female rats. Given that estradiol conjugated with bovine serum albumin is a membrane impermeable compound, these findings suggest that estradiol decreases TMJ nociception by a peripheral nongenomic mechanism. The antinociceptive effect of estradiol was blocked by an estrogen receptor antagonist and by a nitric oxide synthase and a guanilato cyclase inhibitors, but not by a opioid receptor antagonist. These findings suggest that estradiol decreases TMJ nociception in female rats through a peripheral activation of NO-cGMP signaling pathway. Taken together, the findings of this study suggest that the high physiological level of testosterone decreases the risk of male rats develop TMJ pain and that of estradiol decreases TMJ nociception in female rats. Furthermore, TMJ nociception was also decreased by systemic administration of estradiol or progesterone in female and of testosterone in male rats. The antinociceptive effect of sex hormones is mediated by central opioid mechanisms, while peripheral opioid mechanisms mediate the antinociceptive effect of progesterone and testosterone, but not of estradiol. In fact, the administration of estradiol in the TMJ decreases nociception by a peripheral non-genomic mechanism mediated by activation of the nitric oxide-cGMP signaling pathway, but not by opioid receptors.

ASSUNTO(S)

estrogen testosterona sex progesterone testosterone pain progesterona dor estrogenos sexo

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