Gonadal hormones modulate the responsiveness to local ß-blocker-induced antinociception in the temporomandibular joint of male and female rats.

BACKGROUND: We have previously demonstrated that blockade of ß-adrenoreceptors (ß-AR) located in the temporomandibular joint (TMJ) of rats suppresses formalin-induced TMJ nociceptive behaviour in both male and female rats, but female rats are more responsive. In this study, we investigated whether gonadal hormones modulate the responsiveness to local ß-blocker-induced antinociception in the TMJ of rats. METHODS: Co-administration of each of the selective ß1 (atenolol), ß2 (ICI 118.551) and ß3 (SR59230A)-AR antagonists with equi-nociceptive concentrations of formalin in the TMJ of intact, gonadectomized and hormone-treated gonadectomized male and female rats. RESULTS: Atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in all groups tested. However, a lower dose of each ß-AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and testosterone-treated gonadectomized male rats. In the female groups, a lower dose of ß1 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact or gonadectomized rats treated with progesterone or a high dose of oestradiol; a lower dose of ß2 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and gonadectomized rats treated with low or high dose of oestradiol. CONCLUSION: Gonadal hormones may reduce the responsiveness to local ß-blocker-induced antinociception in the TMJ of male and female rats. However, their effect depends upon their plasma level, the subtype of ß-AR and the dose of ß-blockers used.

Blockade of ß1-, ß2- and ß3-adrenoceptors in the temporomandibular joint induces antinociception especially in female rats.

BACKGROUND: Temporomandibular joint (TMJ) receives rich sympathetic innervations that may contribute to TMJ pain through the local release of sympathomimetic amines. The aim of this study was to determine whether blockade of ß-adrenoceptors in the TMJ of male and female rats reduces formalin-induced TMJ nociceptive behaviour. METHODS: We co-administrated each one of the selective ß(1) -, ß(2) - and ß(3) -adrenoceptors antagonists, atenolol, ICI 118.551 and SR59230A, respectively, with formalin in the TMJ of male and proestrus and dioestrus female rats. Because intra-temporomandibular joint formalin induces significantly different concentration-dependent responses among the three groups, with dioestrus females showing greater responses than males or proestrus females, equi-nociceptive formalin concentrations were used to test the effects of the ß-adrenoceptor antagonists. RESULTS: We found that atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in both males and females. However, a lower dose of each ß-adrenoceptor antagonist was sufficient to significantly reduce nociceptive responses in females than in males. Administration of the highest doses of each ß-adrenoceptor antagonist in the TMJ contralateral to that receiving formalin did not affect formalin-induced nociception in males and females, confirming the local action of the ß-adrenoceptor antagonists. CONCLUSIONS: We conclude that blockade of ß-adrenoceptors in the temporomandibular joint suppresses formalin-induced TMJ nociceptive behaviour in both males and females but females are more responsive. These findings suggest that the use of ß-blockers in the treatment of TMJ pain might be of benefit, especially in females.

Peripheral estradiol induces temporomandibular joint antinociception in rats by activating the nitric oxide/cyclic guanosine monophosphate signaling pathway.

Recently, we have reported that high physiological estradiol level during the proestrus phase of the estrous cycle or systemic estradiol administration in ovariectomized rats decreases formalin-induced temporomandibular joint nociception. However, the mechanisms underlying the antinociceptive effect of estradiol are presently unknown. In this study, we used the temporomandibular joint formalin model in rats to investigate whether estradiol decreases nociception by a peripheral non-genomic mechanism, and if so, whether this mechanism is mediated by the activation of the nitric oxide-cyclic guanosine monophosphate signaling pathway and of opioid receptors. The administration of estradiol into the ipsilateral, but not into the contralateral temporomandibular joint significantly reduced formalin-induced temporomandibular joint nociception in ovariectomized and diestrus but not in proestrus females. However, the administration of the estrogen receptor antagonist ICI 182780 into the ipsilateral, but not into the contralateral temporomandibular joint blocked the antinociceptive effect of serum estradiol in proestrus females, suggesting that the physiological effect of estradiol in nociception is mediated, at least in part, by a peripheral mechanism. The administration of estradiol into the ipisilateral temporomandibular joint did not affect formalin-induced nociception in male rats. The antinociceptive effect of temporomandibular joint estradiol administration in ovariectomized and diestrus females was mimicked by estradiol conjugated with bovine serum albumin, which does not diffuse through the plasma membrane, and was blocked by the estrogen receptor antagonist ICI 182780. The administration of the nitric oxide synthase inhibitor (nitro-l-arginine) or of a guanylate cyclase inhibitor (1H-(1,2,4)-oxadiasolo (4,2-a) quinoxalin-1-one) into the ipsilateral, but not into the contralateral temporomandibular joint blocked the antinociceptive effect of estradiol and of estradiol conjugated with bovine serum albumin, while the opioid receptor antagonist naloxone had no effect. These findings suggest that estradiol decreases temporomandibular joint nociception in female rats through a peripheral non-genomic activation of the nitric oxide-cyclic guanosine monophosphate signaling pathway.