Peripheral effect of a kappa opioid receptor antagonist on nociception evoked by formalin injected in TMJ of pregnant rats

The effect of sex hormones on orofacial pain modulation is poorly understood. Therefore, this study aimed to investigate the effect of hormonal changes as a result of pregnancy, as well as that of the kappa (kappa) opioid receptor antagonist on female rats' sensitivity to the temporomandibular joint (TMJ) formalin test. Initially, female rats at estrus and pregnant females on day 19 of pregnancy received a 50 mul formalin (1.5%) injection in the right TMJ. The pregnant females showed a reduction in nociceptive responses to the TMJ formalin test when compared with those at estrus. Then, the selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), was co-administered with the formalin. Next, additional groups received the kappa(200 mug) receptor antagonist or 0.9% NaCl 24 hours prior to the periarticular injection of formalin. Co-administration of nor-BNI with formalin into the TMJ region had no significant effect. The pre-injection of selective kappa-opioid receptor antagonist, nor-BNI, significantly enhanced the nociceptive behavioral responses in pregnant females. When applied in the contralateral TMJ, nor-BNI did not affect the magnitude of the nociceptive response induced by formalin. It can be concluded that: 1) The increase of the sex hormone levels, as result of pregnancy, induces a reduction of nociceptive behavioral responses to the TMJ formalin test; 2) the peripheral kappa opioid receptor activation, by endogenous opioid agonists release, is involved in the antinociception to TMJ formalin test, induced by pregnancy. (C) 2004 Elsevier Inc. All rights reserved.76101177118

Effects of ethanol on deep pain evoked by formalin injected in TMJ of rat

It has been reported that ethanol can alter nociceptive sensitivity from superficial tissues, such as skin and subcutaneous region. However, the influence of ethanol on deep pain conditions is not understood. The aim of this study was to demonstrate the acute, chronic and ethanol withdrawal effects on nociceptive behavioral responses induced by the injection of formalin into the temporomandibular joint (TMJ) region of rats. In experiment 1, rats were injected with ethanol (2,5 g/Kg, IP) or an equal volume of saline 15 min before the administration of formalin (1,5%) into the TMJ. Rats pretreated with ethanol showed a decrease in nociceptive behavioral responses. In experiment 2, rats were given an ethanol solution (6,5%) or tap water to drink for 4 and 10 days. On day 4, the animals (ethanol group) showed amounts of analgesia when submitted to the TMJ formalin test. Tolerance to the antinociceptive effects was observed on day 10. Behavioral hyperalgesia was verified 12 hr after withdrawal in another group that drank ethanol for 10 days. These results show that ethanol can affect the nociceptive responses related to deep pain evoked by the TMJ formalin test. (C) 2003 Published by Elsevier Inc.73263351336

DETERMINATION OF DL50 OF THE SIALOTOXIN-III AND YOUR RELATIONSHIP WITH THE TESTOSTERONE IN MICE

The purpose of this work was to determinate the DL50 of the Sialotoxin III, isolated by PINHEIRO (14), in female and male mice, as well in castrated male mice and female treated by testosterone. Effectively, the Sialotoxin III is a toxic ratio produced by salivary glands of male mice that promotes a lot of biological reactions and death when it is administrated in mice. The DL50 of this toxine on mice was aproximately 133,91 ug/kg, while on females, which are much more sensible, it was 38,36 ug/kg. On the other hand, the orchiectomized animals and females treated by testosterone presented a DL50 of 56,42 ug/kg and 77,72 ug respectively, showing therefore a protector testosterone action in relation to the toxicity of this substance confirming the evidence that the Sialotoxins are dependent androgens.35344945

Peripheral sympathetic component of the temporomandibular joint inflammatory pain in rats

The aim of this study was to further validate our carrageenan-induced temporomanclibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local beta-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of P, but not the blockade of the beta(1)-adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. in the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of beta(2)-adrenoceptors. Perspective: The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating beta(2)-adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs. (c) 2006 by the American Pain Society.71292993

The effects of restraint stress on nociceptive responses induced by formalin injected in rat's TMJ

It has been reported that stress can alter nociception from superficial tissues, such as skin and subcutaneous region. However, the influence of stress on an experimental deep nociception model is not understood. In this study, the temporomandibular joint (TMJ) formalin test was used to evaluate the effects of acute and chronic restraint stress on nociceptive responses in rats. Animals were initially submitted to one session of acute restraint stress (1 h) or exposed to chronic stress (40 days-1 h/day). Then, animals were killed immediately to collect blood for hormonal determinations by radioimmunoassay, or submitted to the TMJ formalin test to evaluate nociception. Rats submitted to acute restraint presented a performance similar to unstressed controls in the TMJ formalin test, whereas chronically stressed rats showed an increase in nociceptive responses. After 40 days of restraint, morphine was injected i.p. (1, 5 mg/kg or saline). The stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. These findings suggest that repeated stress can produce hyperalgesia, which is, at least in part, due to alterations in the activity of opioid systems. This model may help elucidate the underlying neural mechanisms that mediate the effects of repeated stress on orofacial pain. (C) 2005 Elsevier Inc. All rights reserved.82233834

The influence of sex and ovarian hormones on temporomandibular joint nociception in rats

The aim of this study was to investigate the influence of sex and ovarian hormones on formalin- and glutamate-induced temporomandibular joint (TMJ) nociception in rats. The influence of sex and ovarian hormones on the nociceptive behavior induced by formalin or glutamate was virtually the same. The nociceptive behavior of males was similar to that of females in the proestrus phase of the estrous cycle but was significantly lower than that in the diestrus phase. Since the serum level of estradiol but not of progesterone was significantly higher in the proestrus than in the diestrus phase, these data suggest that females with lower endogenous serum level of estradiol have an exacerbation of TMJ nociception. The nociceptive behavior of ovariectomized rats was similar to that of diestrus females and significantly greater than that of proestrus females. Although the administration of estradiol or progesterone in ovariectomized females significantly reduced TMJ nociception, the combination of both hormones did not increase the antinociceptive effect induced by each of them. These findings suggest that estradiol and progesterone decrease TMJ nociception in an independent way. Perspective: We report that ovarian hormones have an antinociceptive effect on the TMJ formalin and glutamate nociceptive behavior models. Therefore, the greater prevalence and severity of TMJ pain in women of reproductive age may be a consequence of hormonal fluctuation during the reproductive cycle, in that during low endogenous estradiol serum level TMJ pain sensitivity is increased, enhancing the risk of females experiencing TMJ pain. (C) 2008 by the American Pain Society.9763063