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1.
Eur J Pain ; 22(3): 572-582, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29226500

RESUMO

BACKGROUND: ß-Blockers reduce temporomandibular joint (TMJ) pain. We asked whether they also reduce TMJ inflammation and, if so, whether this anti-inflammatory effect contributes to its analgesic action. METHODS: We measured many parameters of the inflammatory response after co-administration of the ß-blocker propranolol with the inflammatory agent carrageenan in the TMJ of female rats. We also hypothesized that the activation of ß-adrenoceptors in the TMJ induces nociception mediated, at least in part, by the inflammatory response. To test this hypothesis, we examined the nociceptive response induced by the activation of the ß-adrenoceptors in the TMJ in female rats pretreated with thalidomide and fucoidan. RESULTS: We found that the co-administration of propranolol with carrageenan in the TMJ of female rats significantly reduced several parameters of the inflammatory response induced by carrageenan such as plasma extravasation, neutrophil migration and the release of the pro-inflammatory cytokines TNF-α, IL-1ß and CINC-1. Furthermore, the injection of the ß-adrenergic receptor agonist isoproterenol in the TMJ induced nociception that was significantly reduced by thalidomide, fucoidan and by the co-administration of propranolol but not of the α-adrenergic receptor antagonist phentolamine. CONCLUSIONS: Propranolol has anti-inflammatory effects that contribute to its antinociceptive action in the TMJ of females. SIGNIFICANCE: ß-Blockers have an anti-inflammatory effect on temporomandibular joint (TMJ) that contributes to its analgesic effect. The results of this work suggest that ß-blockers can be used to treat the painful conditions of TMJ, especially when they are associated with an inflammatory process.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Nociceptividade/efeitos dos fármacos , Propranolol/farmacologia , Articulação Temporomandibular/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/farmacologia , Carragenina/farmacologia , Quimiocina CXCL1/efeitos dos fármacos , Quimiocina CXCL1/imunologia , Feminino , Imunossupressores/farmacologia , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Dor/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Fentolamina/farmacologia , Polissacarídeos/farmacologia , Ratos , Ratos Wistar , Articulação Temporomandibular/imunologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Talidomida/farmacologia
2.
Neuroscience ; 286: 37-44, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25451282

RESUMO

We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens µ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens µ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the µ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens µ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain.


Assuntos
Analgésicos/administração & dosagem , Capsaicina/administração & dosagem , Dor Crônica/prevenção & controle , Hiperalgesia/prevenção & controle , Núcleo Accumbens/fisiopatologia , Animais , Dor Crônica/induzido quimicamente , Dinoprostona , Hiperalgesia/induzido quimicamente , Masculino , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Opioides mu/antagonistas & inibidores , Teste de Desempenho do Rota-Rod , Somatostatina/análogos & derivados , Somatostatina/farmacologia
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