The indirect antinociceptive mechanism of 15d-PGJ(2) on rheumatoid arthritis-induced TMJ inflammatory pain in rats

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISInflammation of the temporomandibular joint (TMJ) induced by rheumatoid arthritis (RA) have resulted in persistent pain and caused distress to many patients. Considering that not all patients respond to traditional drugs therapy to RA and it has demonstrated that 15-deoxy-(Delta 12,14)-prostaglandin J(2) (15d-PGJ(2)) into TMJ has a potential peripheral antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ2 in RA-induced TMJ inflammatory hypernociception. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA). RA-induced TMJ hypernociception was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenized. The supernatants were used to evaluate the levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKC epsilon and PKA by western blotting analysis. The intra-articular injection of mBSA, but not phosphate buffered saline (control), in immunized rats induced dose-and time-dependent behavioural nociceptive responses in which the peak of nociceptive responses were obtained by using 10 mu g/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ(2) (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ(2) reduced the RA-induced release of TNF-alpha, IL-1 beta and KC (p < 0.05) as well the expression of PKA and PKC epsilon (p < 0.05). In the present study, we demonstrated that 15d-PGJ(2) was able to reduce the RA-induced TMJ inflammatory hypernociception by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-alpha, IL-1 beta and KC levels and PKA/PKC epsilon expression in the TMJ16811061115FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP [2011/00683-5]Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, Brazil [FAPEMIG PPM 097/09]2011/00683-5PPM097/0

The role of endogenous opioid peptides in the antinociceptive effect of 15-deoxy (delta 12,14)-prostaglandin J(2) in the temporomandibular joint

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe have previously demonstrated that peripheral administration of 15d-PGJ(2) in the Temporomandibular joint (TMJ) of rats can prevent nociceptor sensitization, mediated by peroxisome proliferator activated receptor-gamma (PPAR-gamma), and kappa- and delta- opioid receptors. However, the mechanism that underlies the signaling of PPAR-gamma (upon activation by 15d-PGJ(2)) to induce antinociception, and how the opioid receptors are activated via 15d-PGJ(2) are not fully understood. This study demonstrates that peripheral antinociceptive effect of 15d-PGJ(2) is mediated by PPAR-gamma expressed in the inflammatory cells of TMJ tissues. Once activated by 15d-PGJ(2), PPAR-gamma induces the release of beta-endorphin and dynorphin, which activates kappa- and delta-opioid receptors in primary sensory neurons to induce the antinociceptive effect. (C) 2016 Elsevier Ltd. All rights reserved.We have previously demonstrated that peripheral administration of 15d-PGJ(2) in the Temporomandibular joint (TMJ) of rats can prevent nociceptor sensitization, mediated by peroxisome proliferator activated receptor-gamma (PPAR-gamma), and kappa- and delta- opioid receptors. However, the mechanism that underlies the signaling of PPAR-gamma (upon activation by 15d-PGJ(2)) to induce antinociception, and how the opioid receptors are activated via 15d-PGJ(2) are not fully understood. This study demonstrates that peripheral antinociceptive effect of 15d-PGJ(2) is mediated by PPAR-gamma expressed in the inflammatory cells of TMJ tissues. Once activated by 15d-PGJ(2), PPAR-gamma induces the release of beta-endorphin and dynorphin, which activates kappa- and delta-opioid receptors in primary sensory neurons to induce the antinociceptive effect1102734CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO483988/20121830/20102011/00683-

Low doses of 15d-PGJ2 induce osteoblast activity in a PPAR-gamma independent manner

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOPeroxisome proliferator-activated receptor-gamma (PPAR gamma) regulates both glucose metabolism and bone mass. Evidence suggests that the therapeutic modulation of PPAR gamma with synthetic agonists activity may elicit undesirable effects on bone. However, there is no information regarding its natural agonist 15d-PGJ(2), besides its excellent anti-inflammatory action. In the present study the effects of 15d-PGJ(2) on osteoblastic cells were determined. Osteoblastic cells (MC3T3) were cultured in an osteogenic medium in the presence of 1, 3 or 10 mu M of 15d-PGJ(2) during 21 days and alizarin and Von Kossa staining were employed. The protein expression (type-I collagen, osteonectin, osteopontin, RANKL, osteoprotegerin, HDAC-9c and PPAR-gamma) was evaluated after 3 days in the presence of 15d-PGJ(2) by western blotting and indirect immunofluorescence methods. The production of mineralized extracellular matrix was observed by transmission electron microscopy. After 72 h of culture, the mRNA was extracted for RT-qPCR analysis of RUNX expression. In the presence of all 3 tested 15d-PGJ2 doses, alizarin red and Von kossa staining were positive demonstrating the ability to the osteoblast differentiation. Type-I collagen and osteonectin proteins expression were up-regulated (p < 0.05) after 72 h in the presence of the smaller doses of 15d-PGJ(2). In contrast osteopontin, RANKL and OPG expression did not significantly alter. In the presence of 15d-PGJ(2) it was possible to visualize mineralized nodules in the extracellular matrix confirmed with the increased RUNX mRNA expression. 15d-PGJ(2) at small doses increased the osteoblast activity and the bone-related proteins expression162131138FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP [2010/15014-9]CNPq [471305/2009-0]2010/15014-9471305/2009-

15d-PGJ2-loaded in nanocapsules enhance the antinociceptive properties into rat temporomandibular hypernociception

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOTo verify whether the nanoencapsulation of 15d-PGJ(2) in poly(D,L-lactide-co-glycolide) (PLGA) nanocapsules (15d-PGJ(2)-NC) might potentialize its antinociceptive activity into rats' temporomandibular joint (TMJ). Main methods: Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to evaluate the morphology and suspension of the PLGA nanocapsules. Rats were pretreated (15 min) with an intra-TMJ injection of unloaded 15d-PGJ(2) or 15d-PGJ(2)-NC at concentrations of 10, 100 or 1000 pg followed by an ipsilateral intra-TMJ injection of 1.5% formalin. The nociceptive behavioral response was observed during 45 min: animals were then sacrificed and the periarticular tissue was removed for IL-1 beta measurements. TEM and AFM analyses showed that 15d-PGJ(2)-NC is spherical without any aggregates or adhesion confirming that this formulation is a good drug carrier system for 15d-PGJ(2). Pretreatment with 15d-PGJ(2)-NC (100 and 1000 pg/TMJ), but not unloaded 15d-PGJ(2), was found to significantly decrease the release of IL-1 beta cytokine and the animals' nociceptive behavioral response induced by intra-TMJ injection of formalin. The compound 15d-PGJ(2)-NC might be used as a potential antinociceptive and anti-inflammatory agent to treat temporomandibular disorders in clinical practice9023-24944949FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP [2010/15014-9]CNPq [303080/2010-8]2010/15014-9303080/2010-

Gonadal hormones decrease temporomandibular joint kappa-mediated antinociception through a down-regulation in the expression of kappa opioid receptors in the trigeminal ganglia

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe have previously demonstrated that activation of kappa-opioid receptor located in the temporomandibular joint (TMJ) of rats induces a significantly greater TMJ antinociception in diestrus females than in proestrus females (higher estradiol serum levels than diestrus) and males. These findings indicate that gonadal hormones decrease TMJ kappa-mediated antinociception. The aim of this study was to investigate some of the mechanisms by which gonadal hormones decrease TMJ kappa-mediated anti nociception. Western blot analysis demonstrated a significantly lower kappa-opioid receptor expression in the trigeminal ganglia of intact males than in intact and ovariechtomized (OVX) females and orchidectomized (ORX) males. In females, kappa-opioid receptor expression in the trigeminal ganglia was significantly lower in proestrus than in diestrus and OVX females. Taken together these findings suggest that gonadal hormones, especially male gonadal hormones, down-regulate kappa-opioid receptor expression. Co-application of the NOS inhibitor L-NMMA or the NO-sensitive guanylyl cyclase inhibitor ODQ with the kappa-opioid receptor agonist U50,488 blocked TMJ kappa-mediated antinociception in males and females. These findings suggest that antinociception induced by activation of kappa opioid receptors in the TMJ region is mediated by the L-arginine/NO/cGMP pathway in both sexes. Despite the involvement of the L-arginine/NO/cGMP pathway in TMJ kappa-mediated antinociception in both sexes, gonadal hormones do not diminish the activity of this pathway to decrease TMJ kappa-mediated antinociception. Alternatively, they significantly reduce kappa-opioid receptor expression in the trigeminal ganglia6171-34147FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP [FAPESP 04/00073-9]2004/00073-

Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOPeriodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1 beta, TNF-alpha, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production761223162321FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçãosem informaçã

Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISBones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease. Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg.kg-1 propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1 beta, TNF-alpha and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by ELISA, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro. Propranolol at 0.1 and 5 mg.kg-1 reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg.kg-1 reduced IL-1 beta, TNF-alpha and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc) 1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9. Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters165721402151CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCNPq [471305/2009-0, 303080/2010-8]PAPE-UNIUBE [2009/001]FAPEMIG [097/09]471305/2009-0; 303080/2010-8097/0

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

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe 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. © 2011 European Federation of International Association for the Study of Pain Chapters.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 hormones162204216CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãosem informaçã

Secreted osteoclastogenic factor of activated T cells (SOFAT), a novel osteoclast activator, in chronic periodontitis

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOA novel activated human T cell-secreted cytokine, referred as secreted osteoclastogenic factor of activated T cells (SOFAT), that induce osteoclastogenesis in a RANKL-independent manner was recently described. This study evaluated the role of SOFAT in periodontal tissues and periodontitis. Gingival biopsies were harvested from systemically healthy non-periodontitis (n = 15) and chronic periodontitis patients (n = 15). The mRNA and protein levels of SOFAT were measured by qPCR and by enzyme-linked immunosorbent assay, respectively. Moreover, RAW 264.7 cells were cultured with SOFAT or Receptor activator of nuclear factor-kB ligand (RANKL) and stained for tartrate-resistant acid phosphatase (TRAP). Also, mice received a palatal injection between the first and second upper molar of SOFAT (100 ng/ml) or saline solution (0.9%). The upper jaw was removed, histologically processed and stained with hematoxilin and eosin to observe the presence of osteoclast-like cells. The mRNA and protein levels of SOFAT were significantly higher in the gingival tissue of the periodontitis group when compared to non-periodontitis one (p < 0.05). In addition, SOFAT potently induced TRAP-positive multinucleated cell formation by RAW 264.7 cells as well as induced the formation of osteoclast-like cells in the periodontal ligament in mice. The present study demonstrated that SOFAT may play an important role in periodontitis. (c) 2013 American Society for Histocompatibility and Immunogenetics747861866CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCNPq [471305/2009-0]471305/2009-

Involvement of temporomandibular joint P2x3 and P2x2/3 receptors in carrageenan-induced inflammatory hyperalgesia in rats

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe aim of this study was to investigate the role of P2X3, P2X2/3 and P2X7 receptors in the development of TMJ hyperalgesia induced by carrageenan. We also investigated the expression of mRNA of P2X7 receptors in the trigeminal ganglia and the existence of functional P2X7 receptors in the rat's TMJ. The P2X1, P2X3 and P2X2/3 receptor antagonist TNP-ATP, but not the selective P2X7 receptor antagonist A-438079, significantly reduced carrageenan-induced TMJ inflammatory hyperalgesia. The qPCR assay showed that mRNA of P2X7 receptors are expressed in the trigeminal ganglia but this expression is not increased by the inflammation induced by carrageenan in the TMJ region. The P2X7 receptor agonist BzATP induced TMJ inflammatory hyperalgesia that was significantly reduced by pretreatment with dexamethasone. These results indicate that P2X3 and P2X2/3 but not P2X7 receptors are involved in carrageenan-induced TMJ inflammatory hyperalgesia. However, functional P2X7 receptors are expressed in the TMJ region. The activation of these receptors by BzATP sensitizes the primary afferent nociceptors in the TMJ through the previous release of inflammatory mediators. The findings of this study point out P2X3 and P2X2/3 receptors, but not P2X7 receptors, as potential targets for the development of new analgesic drugs to control TMJ inflammatory pain.The aim of this study was to investigate the role of P2X3, P2X2/3 and P2X7 receptors in the development of TMJ hyperalgesia induced by carrageenan. We also investigated the expression of mRNA of P2X7 receptors in the trigeminal ganglia and the existence of functional P2X7 receptors in the rat's TMJ. The P2X1, P2X3 and P2X2/3 receptor antagonistTNP-ATP, but not the selective P2X7 receptor antagonist A-438079, significantly reduced carrageenan-induced TMJ inflammatory hyperalgesia. The qPCR assay showed that mRNA of P2X7 receptors are expressed in the trigeminal ganglia but this expression is not increased by the inflammation induced by carrageenan in the TMJ region. The P2X7 receptor agonist BzATP induced TMJ inflammatory hyperalgesia that was significantly reduced by pretreatment with dexamethasone. These results indicate that P2X3 and P2X2/3 but not P2X7 receptors are involved in carrageenan-induced TMJ inflammatory hyperalgesia. However, functional P2X7 receptors are expressed in the TMJ region. The activation of these receptors by BzATP sensitizes the primary afferent nociceptors in the TMJ through the previous release of inflammatory mediators. The findings of this study point out P2X3 and P2X2/3 receptors, but not P2X7 receptors, as potential targets for the development of new analgesic drugs to control TMJ inflammatory pain6451-37985FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã