Local Sustained Delivery of Anti-IL-17A Antibodies Limits Inflammatory Bone Loss in Murine Experimental Periodontitis.

Periodontal disease (PD) is a chronic destructive inflammatory disease of the tooth-supporting structures that leads to tooth loss at its advanced stages. Although the disease is initiated by a complex organization of oral microorganisms in the form of a plaque biofilm, it is the uncontrolled immune response to periodontal pathogens that fuels periodontal tissue destruction. IL-17A has been identified as a key cytokine in the pathogenesis of PD. Despite its well documented role in host defense against invading pathogens at oral barrier sites, IL-17A-mediated signaling can also lead to a detrimental inflammatory response, causing periodontal bone destruction. In this study, we developed a local sustained delivery system that restrains IL-17A hyperactivity in periodontal tissues by incorporating neutralizing anti-IL-17A Abs in poly(lactic-coglycolic) acid microparticles (MP). This formulation allowed for controlled release of anti-IL-17A in the periodontium of mice with ligature-induced PD. Local delivery of anti-IL-17A MP after murine PD induction inhibited alveolar bone loss and osteoclastic activity. The anti-IL-17A MP formulation also decreased expression of IL-6, an IL-17A target gene known to induce bone resorption in periodontal tissues. This study demonstrates proof of concept that local and sustained release of IL-17A Abs constitutes a promising therapeutic strategy for PD and may be applicable to other osteolytic bone diseases mediated by IL-17A-driven inflammation.

The blockade of kappa opioid receptors exacerbates alveolar bone resorption in rats.

OBJECTIVES: Bone resorption associated to chronic diseases, such as arthritis and periodontitis, results from exacerbated immuno-inflammatory host response that leads to tissue breakdown. The significance of opioid pathways as endogenous modulators of inflammatory events has already been described. Thus, the aim of this work is to determine whether some of the main three opioid receptors are endogenously activated to prevent bone loss during experimentally-induced alveolar bone resorption. DESIGN: This study used an experimental model of alveolar bone resorption induced by ligature in rats. A silk thread was placed around the 2nd maxillary molar of male Wistar rats. In the 3rd, 4th and 5th day after ligation the rats received a local injection of different concentrations of opioid antagonists Cyprodime, Naltrindole, or Nor-binaltorphimine, which specifically block mü, delta and kappa opioid receptors, respectively. In the 7th experimental day, rats were euthanized and their maxillae collected for evaluation of alveolar bone and fiber attachment loss, morphometric counting of osteoclasts and osteoblasts, as well as the levels of cytokines IL-1ß, IFN-γ, and IL-6 by ELISA. RESULTS: Selective antagonism of kappa opioid receptors, but not mü and delta, exacerbated alveolar bone resorption induced by ligature in rats. The increased bone loss associated with higher number of osteoclasts surrounding alveolar bone, although osteoblasts' counting remained unchanged. The concentrations of IL-1ß and IL-6 in periodontal tissues were also significantly higher in the rats treated with the kappa antagonist. CONCLUSION: Inhibiting kappa opioid receptors exacerbates alveolar bone resorption.

Koh group influence on titanium surfaces and pure sol-gel silica for enhanced osteogenic activity.

Although, the excellent level of success of titanium surfaces is based on the literature, there are some biological challenges such as unfavorable metabolic conditions or regions of poor bone quality where greater surface bioactivity is desired. Seeking better performance, we hypothesized that silica-based coating via sol-gel route with immersion in potassium hydroxide basic solution induces acceleration of bone mineralization. This in vitro experimental study coated titanium surfaces with bioactive glass synthesized by route sol-gel via hydrolysis and condensation of chemical alkoxide precursor, tetraethylorthosilicate (TEOS) and/or deposition of chemical compound potassium hydroxide (KOH) to accelerate bone apposition. The generated surfaces titanium(T), titanium with potassium hydroxide deposition (T + KOH), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis (TEOS), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis with potassium hydroxide deposition (TEOS + KOH) were characterized by 3D optical profilometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle by the sessile drop method, x-ray excited photoelectron spectroscopy (XPS) and energy dispersive x-ray spectrometer (EDX). The addition of the KOH group on the pure titanium (T) or bioactive glass (TEOS) surfaces generated a tendency for better results for mineralization. Groups covered with bioactive glass (TEOS, TEOS + KOH) tended to outperform even groups with titanium substrate (T, T + KOH). The addition of both, bioactive glass and KOH, in a single pure titanium substrate yielded the best results for the mineralization process.

A importância da saúde bucal em pacientes hospitalizados: uma revisão / The importance of oral health in hospitalized patients: a review

Existe uma relação importante entre o estado de saúde bucal e aquele da saúde geral. Em pacientes hospitalizados essa relação assume importância ainda maior, pois o indivíduo encontra-se fragilizado e, muitas vezes, é incapaz de realizar uma higiene bucal adequada. O presente trabalho trata-se de uma revisão de literatura que tem como objetivo discutir os principais problemas bucais apresentados por pacientes hospitalizados, principalmente aqueles que ficam por longo período de tempo. A maioria dos trabalhos encontrados relata que a saúde bucal de pacientes hospitalizados por longos períodos é precária e que isso afeta diretamente a saúde geral dos mesmos. Concluiu-se que uma saúde bucal adequada pode melhorar a resposta do paciente ao tratamento médico e que a presença de cirurgiões dentistas nas equipes multiprofissionais dos hospitais é de extrema importância para a implementação de protocolos clínicos de conduta visando tanto a prevenção quanto a recuperação da saúde bucal dos pacientes hospitalizados

There is an important relationship between the state of oral health and that of overall health. In hospitalized patients this relationship is even more important because the individual is debilitated and,most of the time, is unable to perform an adequate oral hygiene. This work is a literature review that aims to discuss the main oral problems presented by hospitalized patients, especially those who stay for longer period of time. Most studies found that the oral health of hospitalized patients for long periods is precarious and that this directly affects the overall health of them. It leads to the conclusion that adequate oral health can improve a patient's response to medical treatment and that the presence of dentists in multidisciplinary teams of hospitals is of extreme importance for the implementation of clinical management protocols aimed at both prevention and recovery of oral health of hospitalized patients

Endogenous opioids regulate alveolar bone loss in a periodontal disease model.

AIM: The anti-inflammatory effects of exogenous opioid compounds have been demonstrated in several conditions. Nevertheless, the function of endogenous opioid peptides released by the host during inflammatory processes deserves further characterization. The aim of this study was to verify whether endogenous opioids are involved in the progression of the inflammatory alveolar bone loss induced by ligature in rats. MAIN METHODS: The experimental model of periodontal disease (PD) induced by ligature in rats was used throughout the study. A silk ligature was placed around the 2nd upper molar of male Holtzman rats, for 7 days. Rats received different doses of either the non-selective opioid antagonist naloxone or vehicle, locally into the afflicted gingival tissue, from the 3rd to the 5th day after ligature placement. In the 7th experimental day, rats were euthanized and their maxillae were collected for evaluation of alveolar bone and fiber attachment loss, presence of neutrophils (myeloperoxidase assay), osteoclast amount, and levels of cytokines IL-6, TNF-α, IL-8 and IL-10 in periodontal tissues. KEY FINDINGS: Naloxone increased alveolar bone loss significantly, in a dose-dependent manner, in relation to vehicle-treated rats. In contrast, the opioid antagonist did not affect the loss of fiber attachment. The treatment with naloxone also induced a significant increase in myeloperoxidase levels, osteoclast number and cytokines in periodontal tissues of rats with ligature-induced PD. SIGNIFICANCE: Endogenous opioids protect the host from the progression of inflammatory alveolar bone loss that occurs in chronic periodontitis.

Antinociceptive response in transgenic mice expressing rat tonin.

Angiotensin II (Ang II) may be produced directly from angiotensinogen by tonin. Studies have demonstrated that Ang II and its metabolite Ang-(1-7) produce antinociception in pain animal models. The aim of the present study was to determine whether the transgenic mice that express rat tonin (TGM(rTon)) show altered nociceptive behavior and investigate the possible involvement of angiotensin metabolites. Nociception was evaluated using the thermal tail-flick and chemical acetic acid writhing tests, and the drugs were administered by intracerebroventricular and subcutaneous pathways, respectively. Probabilities less than 5% (P<0.05) were considered to be statistically significant (t test; ANOVA/Bonferroni's test). The results demonstrate that the transgenic mice showed an antinociceptive effect in the tail-flick and acetic acid writhing tests. In addition, it was observed that losartan, an AT1 receptor antagonist and A-779 (D-Ala7-Ang-(1-7)), a Mas receptor antagonist attenuated the antinociceptive behavior. Our data suggest that the Ang II produced in TGM(rTon) induces antinociception via the AT1 receptor, while the Ang-(1-7) produced from Ang II induced antinociception via the Mas receptor.

δ-Opioid receptor agonist SNC80 induces central antinociception mediated by Ca2+ -activated Cl- channels.

OBJECTIVES: The aim of this study was to determine whether Ca(2+)-activated Cl(-) channels (CaCCs) are involved in central antinociception induced by the activation of µ-, δ- and κ-opioid receptors. METHODS: The nociceptive threshold for thermal stimulation was measured using the tail-flick test in Swiss mice. The drugs were administered via the intracerebroventricular route. Probabilities values of P < 0.05 were considered to be statistically significant (analysis of variance/Bonferroni test). KEY FINDINGS: The results demonstrate that exposure to the CaCC blocker niflumic acid (2, 4 and 8 µg) partially reverses the central antinociception induced by the δ-opioid receptor agonist SNC80 ((+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide; 4 µg). In contrast, niflumic acid did not modify the antinociceptive effect of the µ-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (0.5 µg) or κ-opioid receptor agonist bremazocine (4 µg). CONCLUSIONS: These data provide evidence for the involvement of CaCCs in δ-opioid receptor-induced central antinociception resulting from receptor activation by the agonist SNC80. CaCC activation does not appear to be involved when µ- and κ-opioid receptors are activated.

Mast cell in dental pulp: does it have a role / Mastócitos na polpa dental: eles têm uma função

Os mastócitos desempenham um importante papel em uma variedade de processos biológicos e participam, ativamente, da resposta inflamatória. Existe, no entanto, uma controvérsia na literatura a respeito da presença de mastócitos em polpas dentais. O presente trabalho procurou responder essa controvérsia no que se refere à presença de mastócitos no tecido pulpar de ratos e humanos em condições normais e durante a inflamação. Para isso, polpas inflamadas e não inflamadas de humanos e ratos foram coletadas e analisadas, utilizando-se a técnica histoquímica do azul de toluidina e a técnica de imunohistoquímica. Nossos resultados mostraram a ausência de mastócitos em polpas dentais de ratos e humanos tanto em condições normais quanto durante a inflamação. O papel dos mastócitos na resposta inflamatória da polpa dental não é claro. Fatores de crescimento e citocinas envolvidas na sua migração, desenvolvimento e sobrevivência podem estar ausentes no tecido pulpar e necessitam de futuras investigações.

Mast cells play an important role in a variety of biological processes and actively participate in the inflammatory response. There is a controversy in the literature whether mast cells are present in dental pulp. In this investigation we sought to answer the question concerning the presence of mast cells in human and rat dental pulp tissues, under normal and inflammatory conditions. Human and rat dental pulp under normal and inflammatory conditions were analyzed using toluidine blue histochemistry and immunohistochemistry techniques. Our results showed that inflamed and non-inflamed dental pulps neither from humans nor from rats presented mast cells. The role of mast cells in the inflammatory dental pulp response is not clear. Growth factors and cytokines involved in their migration, development and survival could be absent in this tissue and need further investigations.

Inflammation mobilizes local resources to control hyperalgesia: the role of endogenous opioid peptides.

The aim of the present study was to investigate the mechanisms underlying the endogenous control of nociception at a peripheral level during inflammation. Using a pharmacological approach and the rat paw pressure test, we assessed the effect of an intraplantar injection of naloxone, an opioid receptor antagonist, and bestatin, an aminopeptidase inhibitor, on hyperalgesia induced by carrageenan, which mimics an inflammatory process, or prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Naloxone induced a significant and dose-dependent (25, 50 or 100 µg) increase in carrageenan-induced hyperalgesia, but not PGE(2)-induced hyperalgesia. Bestatin (400 µg/paw) significantly counteracted carrageenan-induced hyperalgesia, inducing an increase in the nociceptive threshold compared to control, but it did not modify hyperalgesia induced by PGE(2) injection into the rat paw. Positive ß-endorphin immunoreactivity was increased in paw inflammation induced by carrageenan in comparison with the control group. However, PGE(2) did not significantly alter the immunostained area. These results provide evidence for activation of the endogenous opioidergic system during inflammation and indicate that this system regulates hyperalgesia through a negative feedback mechanism, modulating it at a peripheral level.

Peripheral antinociception induced by δ-opioid receptors activation, but not µ- or κ-, is mediated by Ca²âº-activated Cl⁻ channels.

Studies have demonstrated that the L-arginine/NO/cGMP pathway and the potassium and calcium channels are involved in the mechanisms underlying opioid receptor activation. As additional pathways may participate in the observed antinociceptive effects following opioid exposure, the aim of our study was to determine whether Ca(2+)-activated Cl(-) channels (CaCCs) are involved in peripheral antinociception induced by µ-, δ- and κ-opioid receptor activation. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (PGE(2), 2 µg). Nociceptive thresholds to pressure (grams) were measured using an algesimetric apparatus 3h following injection. The µ-opioid receptor agonist morphine (200 µg), δ-opioid receptor agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80, 80 µg), κ-opioid receptor agonist bremazocine (50 µg), CaCCs blocker niflumic acid (8-64 µg), CaCCs blocker 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB, 32-128 µg), nitric oxide donor sodium nitroprusside (SNP, 500 µg) and cGMP exogenous analogs dibutyryl cGMP (db-cGMP, 100 µg) were also administered into the paw. The CaCCs blocker niflumic acid and NPPB partially reversed the peripheral antinociception induced by exposure to the SNC80 in a dose-dependent manner. In contrast, niflumic acid did not modify the antinociceptive effect observed following exposure to morphine or bremazocine. Additionally, the peripheral antinociception induced by the NO donor SNP or by db-cGMP was not inhibited by niflumic acid. These results provide evidence for the involvement of CaCCs in the peripheral antinociception induced by SNC80. CaCCs activation does not appear to be involved when µ- and κ-opioid receptors are activated. In addition, we did not observe a link between CaCCs and the L-arginine/NO/GMPc pathway.

Peripheral kappa opioid receptors activation reduces alveolar bone loss in rats by modulating interleukin-6 and -10.

OBJECTIVE: The beneficial effects of kappa opioid agonist U-50,488 in preventing periodontal disease (PD) progression in rats have already been described, but its mechanism of action is unknown. The present study evaluated the expression of TNF-α, IL-6, IL-8 and IL-10 in the gingival tissues of rats with ligature-induced PD, treated with U-50,488. It also correlated the effects of this agonist with myeloperoxidase (MPO) activity and the presence of osteoclasts. DESIGN: Male Holtzman rats weighing 250-300 g were divided into four groups: (1) control, (2) ligature, (3) ligature+saline and (4) ligature+kappa agonist. Experimental PD was induced by placing a sterile silk ligature around the 2nd left upper molar. Rats from groups 3 to 4 were locally administered with either saline or U-50,488, respectively, from day 3 to day 5 following ligation. After 5 or 11 days, the rats were euthanized and periodontal tissue samples were collected for histological and morphometric analysis and for determination of TNF-α, IL-6, IL-8, IL-10 and MPO. RESULTS: Ligature placement induced significant alveolar bone loss. The number of osteoclasts, degree of MPO activity, IL-6, IL-8 and TNF-α expression were also increased by PD. U-50,488 reduced both bone loss and the number of osteoclasts, but did not alter histological inflammatory infiltrate or MPO activity. U-50,488 significantly reduced IL-6 and increased IL-10 levels, but did not affect TNF-α and IL-8. CONCLUSION: Lowering the levels of IL-6 and increasing IL-10 are important mechanisms by which U-50,488 reduces alveolar bone loss in ligature-induced periodontal disease.

(99m)Tc-labeled-1-thio-beta-d-glucose as a new tool to temporomandibular joint inflammatory disorders diagnosis.

AIM: The aim of this study was to evaluate early detection of temporomandibular joint (TMJ) inflammatory changes based on 1-thio-beta-d-glucose radiolabeled with technetium-99m. METHOD: The method applied a TMJ inflammation model in rats followed by radiopharmaceutical synthesis, intravenous administration of (99m)Tc-1-TG and kinetic scintigraphy imaging. RESULTS: Results show a significant difference of (99m)Tc-1-TG uptake between inflamed TMJ and the control joint. The biodistribution of (99m)Tc-1-TG by images showed the kidneys' excretion. CONCLUSION: As conclusion, (99m)Tc-1-TG is a helpful tool in TMJ inflammatory process detection.

Central antinociception induced by mu-opioid receptor agonist morphine, but not delta- or kappa-, is mediated by cannabinoid CB1 receptor.

BACKGROUND AND PURPOSE: It has been demonstrated that cannabinoids evoke the release of endogenous opioids to produce antinociception; however, no information exists regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids are involved in central antinociception induced by activation of mu-, delta- and kappa-opioid receptors. EXPERIMENTAL APPROACH: Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. Morphine (5 microg), SNC80 (4 microg), bremazocine (4 microg), AM251 (2 and 4 microg), AM630 (2 and 4 microg) and MAFP (0.1 and 0.4 microg) were administered by the intracerebroventricular route. KEY RESULTS: The CB(1)-selective cannabinoid receptor antagonist AM251 completely reversed the central antinociception induced by morphine in a dose-dependent manner. In contrast, the CB(2)-selective cannabinoid receptor antagonist AM630 did not antagonize this effect. Additionally, the administration of the anandamide amidase inhibitor, MAFP, significantly enhanced the antinociception induced by morphine. In contrast, the antinociceptive effects of delta- and kappa-opioid receptor agonists were not affected by the cannabinoid antagonists. The antagonists alone caused no hyperalgesic or antinociceptive effects. CONCLUSIONS AND IMPLICATIONS: The results provide evidence for the involvement of cannabinoid CB(1) receptors in the central antinociception induced by activation of mu-opioid receptors by the agonist morphine. The release of endocannabinoids appears not to be involved in central antinociception induced by activation of kappa- and delta-opioid receptors.

Myeloperoxidase content is a marker of systemic inflammation in a chronic condition: the example given by the periodontal disease in rats.

The study aimed to evaluate the suitability of myeloperoxidase (MPO) content as a local indicator of chronic inflammation, using the periodontal disease model. Anesthetized adult male Holtzman rats had their second left maxilar molar tied by a thread for 11 days and were then killed. Blood samples and photographic images from histopathological inflamed and noninflamed (contralateral) neighboring gingivomucosal specimens were collected for cell counts and MPO level analysis. Diseased animals were also treated with pharmacological tools such as the anti-inflammatory drug celecoxib or the opioid morphine. Increased blood neutrophils and local cell numbers characterized diseased animals. However, local MPO content was increased in inflamed and noninflamed tissues from diseased animals. Celecoxib and morphine reduced blood neutrophils and bilateral MPO content, but only celecoxib reduced local cell numbers in diseased animals. It is concluded that MPO content is a good indicator of a systemic rather than a local inflammation in a chronic inflammatory condition.

Local opioids in a model of periodontal disease in rats.

There is growing evidence for the participation of opioid receptors in the development of inflammation. The present study was designed to clarify the role played by opioid receptors in periodontal disease. Periodontal disease was induced by placing a sterile silk ligature around the cervix of the second maxillary tooth on day 0. Morphine was administered either systemically or locally before and after the onset of periodontal disease. The results showed that in both patterns, morphine treatment reduced fiber attachment and alveolar bone loss, without affecting the increased leukocyte count in the gingivae. Naltrexone, a specific opioid antagonist, reversed the inhibitory effects induced by morphine in diseased rats, while the increased number of inflammatory cells remained unaffected. These results point to a possible role for local opioids in experimental periodontal disease.

Inhibition of apical root resorption by calcium hydroxide during orthodontic treatment: a case report

Apical root resorption is a common outcome of orthodontic treatment. The present article reports a case of absence of apical root resorption in a left maxillary lateral incisor filled with calcium hydroxide paste throughout orthodontic movement. After orthodontic treatment was completed the tooth was subsequently obturated with gutta-percha and the patient followed for 18 months. The presence of a periapical lesion and the properties of calcium hydroxide as a root resorption inhibitor were decisive for such an approach in the presented case. Also, the role played by the vital dental pulp in the resorptive process was discussed.

Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity.

Actinobacillus actinomycetemcomitans produces a leukotoxin (Ltx) that kills leukocyte function-associated antigen-1 (LFA-1)-bearing cells from man, the Great Apes and Old World monkeys. The unique specificity of Ltx for the beta2 integrin, LFA-1, suggests it is capable of providing insight into the pathogenic mechanisms of Ltx and other RTX toxins. Using the Jurkat T cell line and an LFA-1-deficient Jurkat mutant (Jbeta2.7) as models, we found the initial effect of Ltx is to elevate cytosolic Ca2+ [Ca2+]c, an event that is independent of the Ltx/LFA-1 interaction. [Ca2+]c increases initiate a series of events that involve the activation of calpain, talin cleavage, mobilization to, and subsequent clustering of, LFA-1 in cholesterol and sphingolipid-rich regions of the plasma membrane known as lipid rafts. The association of Ltx and LFA-1 within lipid rafts is essential for cell lysis. Jbeta2.7 cells fail to accumulate Ltx in their raft fractions and are not killed, while cholesterol depletion experiments demonstrate the necessity of raft integrity for Ltx function. We propose that toxin-induced Ca2+ fluxes mobilize LFA-1 to lipid rafts where it associates with Ltx. These findings suggest that Ltx utilizes the raft to stimulate an integrin signalling pathway that leads to apoptosis of target cells.

Efeitos do verniz com flúor Duraphat na prevençäo da cárie em pacientes com paralisia cerebral / Effects of Duraphat fluoride varnish in the prevention of dental caries in patients with cerebral palsy

O objetivo deste estudo foi avaliar os efeitos do verniz com flúor Duraphat na prevençäo da cárie e na remineralizaçäo de lesöes de mancha branca ativa em pacientes com paralisia cerebral. Neste trabalho, foram selecionados trinta e cinco indivíduos de oito a dezoito anos, que foram divididos em dois grupos: teste e controle. Realizaram-se duas aplicaçöes do verniz Duraphat em dentes decíduos e permanentes totalmente erupcionados, com intervalo de 5 meses, e os resultados clínicos obtidos foram submetidos à análise estatística. Nesta pesquisa, concluímos que a aplicaçäo do verniz com flúor Duraphat foi eficaz na prevençäo da cárie e na reminralizaçäo de lesöes de mancha branca ativa e que o intervalo das suas aplicaçöes foi considerado muito longo em pacientes com paralisia cerebral

Controle da dor em odontologia: os antigos e os novos inibidores das cicloxigenases (COX6) / Pain control in dentistry: the old and the new cyclooxygenase (COX) inhibitors

A dor é uma queixa freqüente na clínica odontológica. Ela pode decorrer de procedimentos cirúrgicos, manipulação de canais radiculares ou mesmo estar associada a desordens da articulação temporomandibular. Como, na maioria dos casos, a dor está associada à inflamação, antiinflamatórios não esteróides (AINES) ou drogas do grupo da aspirina são indicados para o seu alívio. Os AINES mais antigos inibem inespecificamente as enzimas ciclooxigenases (COXs), tendo, como conseqüência, a inibição da síntese de prostaglandinas, importantes substâncias endógenas envolvidas tanto em respostas fisiológicas protetoras (associadas à COX-1), como também, em respostas de dor e de inflamação (associadas à COX-2). Nessa perspectiva, foram desenvolvidos pela indústria farmacêutica dois novos medicamentos inibidores específicos da COX-2, o celecoxib (Celebra, Pfizer) e o refecoxib (Vioxx, MSD). Como o celecoxib e o rofecoxib já podem ser encontrados no mercado brasileiro, o objetivo do presente trabalho é apresentar revisão sobre o uso dos inibidores inespecíficos de ciclooxigenases (AINES) mais antigos, bem com apresentar o potencial terapêutico dos novos AINES (refecoxib e celecoxib) no tratamento da dor em Odontologia