RESUMO
This study evaluated the effect of systemic administration of omega-3 on the expression of interleukins IL-1ß and IL-10 and tumour necrosis factor alpha (TNF-α) and on the thickness of cartilage in the temporomandibular joint (TMJ) inflammatory model induced by complete Freund's adjuvant (CFA). Thirty-two adult rats were divided equally into four groups: control, CFA (induced arthritis), and induced arthritis animals treated with dexamethasone or omega-3. The TMJs were then removed and assigned to histomorphometric analysis or immunoassay. The Kruskal-Wallis test with Dunn post hoc test was applied to the data; the significance level was set at 5%. IL-1ß levels (median; interquartile range) were higher (P<0.0001) in the CFA group (46.4 ng/ml; 39.4-53.3) than in the control group (1.81 ng/ml; 1.5-5.4), but there were no differences between the control, omega-3, and dexamethasone groups. TNF-α levels were also higher (P<0.0001) in the CFA group (122.7 ng/ml; 92.9-284.7) than in the control group (29.1 ng/ml; 23.7-31.3). IL-10 levels were lowest (P<0.0001) in the CFA group (73.5 ng/ml; 52.8-90.5), and no differences were found amongst the other groups. In conclusion, omega-3 successfully reduced the damage in the TMJ of induced arthritis rats. Further investigations are warranted to confirm whether the administration of omega-3 has a comparable effect to glucocorticoids in rheumatoid arthritis patients.
Assuntos
Ácidos Graxos Ômega-3 , Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Animais , Ácidos Graxos Ômega-3/uso terapêutico , Adjuvante de Freund , Humanos , Projetos Piloto , Ratos , Membrana Sinovial , Transtornos da Articulação Temporomandibular/tratamento farmacológicoRESUMO
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 hormones.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite/tratamento farmacológico , Artrite/patologia , Hormônios Esteroides Gonadais/farmacologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Transtornos da Articulação Temporomandibular/patologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/metabolismo , Modelos Animais de Doenças , Feminino , Hormônios Esteroides Gonadais/uso terapêutico , Masculino , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Inflammation 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-Δ12,14-prostaglandin J2 (15d-PGJ2) 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. METHODS: 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)-α, interleukin (IL)-1ß and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKCε and PKA by western blotting analysis. RESULTS: 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 µg/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ2 (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ2 reduced the RA-induced release of TNF-α, IL-1ß and KC (p < 0.05) as well the expression of PKA and PKCε (p < 0.05). CONCLUSIONS: In the present study, we demonstrated that 15d-PGJ2 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-α, IL-1ß and KC levels and PKA/PKCε expression in the TMJ.
Assuntos
Analgésicos/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Prostaglandina D2/análogos & derivados , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Analgésicos/uso terapêutico , Animais , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Quimiocinas/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/fisiopatologia , Interleucina-1beta/metabolismo , Masculino , Medição da Dor/efeitos dos fármacos , Prostaglandina D2/farmacologia , Prostaglandina D2/uso terapêutico , Proteína Quinase C-épsilon/metabolismo , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/fisiopatologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND AND PURPOSE: Bones 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. EXPERIMENTAL APPROACH: 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-1ß, TNF-α and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-κ 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. RESULTS: 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-1ß, TNF-α 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. CONCLUSIONS AND IMPLICATIONS: Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Propranolol/administração & dosagem , Fosfatase Ácida/antagonistas & inibidores , Fosfatase Ácida/genética , Perda do Osso Alveolar/prevenção & controle , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Catepsina K/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Colágeno Tipo I/metabolismo , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Hemodinâmica/efeitos dos fármacos , Inflamação/prevenção & controle , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Masculino , Metaloproteinase 9 da Matriz/genética , Camundongos , Fatores de Transcrição NFATC/antagonistas & inibidores , Osteoclastos/patologia , Peptídeos/metabolismo , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fosfatase Ácida Resistente a Tartarato , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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 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.