Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos
Ano de defesa: | 2009 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/8949 |
Resumo: | Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (DE50=0.04 (0.01-0.11) mg/paw) and edema (DE50=0.08 (0.04-0.16) mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor antagonist SB366791 largely inhibited nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as the pretreatment with the tachykinin NK1 receptor antagonist RP 67580 also significantly reduced MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeat treatment with compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively inhibited nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin and tryptase in the injected tissue, confirming mast cell degranulation Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception, of MSU. Finally, the inhibition of tryptase activity was capable of largely reducing either MSU-induced nociception or edema. Collectively, the present findings demonstrate that MSU produces a nociceptive and edematogenic response mediated by TRPV1 receptor activation and mast cell degranulation. |
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2010-12-012010-12-012009-08-14HOFFMEISTER, Carin Gorete Hendges. Role of TRPV1 on nociception and edema induced by monosodium urate crystals in rats. 2009. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009.http://repositorio.ufsm.br/handle/1/8949Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (DE50=0.04 (0.01-0.11) mg/paw) and edema (DE50=0.08 (0.04-0.16) mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor antagonist SB366791 largely inhibited nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as the pretreatment with the tachykinin NK1 receptor antagonist RP 67580 also significantly reduced MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeat treatment with compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively inhibited nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin and tryptase in the injected tissue, confirming mast cell degranulation Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception, of MSU. Finally, the inhibition of tryptase activity was capable of largely reducing either MSU-induced nociception or edema. Collectively, the present findings demonstrate that MSU produces a nociceptive and edematogenic response mediated by TRPV1 receptor activation and mast cell degranulation.A gota é caracterizada pela deposição de cristais de urato monossódico (MSU) nas articulações. Apesar de ser um dos mais dolorosos tipos de artrite, os mecanismos responsáveis pela indução da dor durante os ataques agudos de gota são pouco entendidos. No presente estudo, objetivamos investigar o papel do receptor TRPV1 na nocicepção e edema induzidos por cristais de MSU em ratos. Assim, demonstramos que o MSU causa nocicepção (DE50=0.04 (0.01-0.11) mg/pata) e edema dependentes da dose (DE50=0.08 (0.04-0.16) mg/pata) quando injetado na pata dos ratos. O tratamento com o antagonista seletivo do receptor vanilóide TRPV1 SB 366791 inibiu significativamente as respostas nociceptiva e edematogênica causadas pelo MSU. De maneira semelhante, a dessensibilização de fibras aferentes sensíveis a capsaicina bem como o tratamento com o antagonista do receptor para taquicinina NK1 RP67580 também reduziram significativamente a nocicepção e o edema induzidos pelo MSU. Sabendo que estudos prévios demonstraram que MSU induz a estimulação de mastócitos, nós investigamos a participação destas células nos efeitos do MSU. A desgranulação prévia de mastócitos por tratamento repetido com o composto 48/80 reduziu a nocicepção e o edema induzidos pelo MSU assim como os níveis de histamina e serotonina no tecido injetado. Adicionalmente, o tratamento com o estabilizador de membrana de mastócitos cromolina, reduziu efetivamente as respostas nociceptivas e edematogênicas ao MSU. A administração de MSU induziu a liberação de histamina, serotonina e triptase no tecido injetado, confirmando a desgranulação mastocitária. Além disso, o antagonismo de receptores histaminérgicos H1 e serotoninérgicos, reduziram o edema, mas não a nocicepção causados pelo MSU. Finalmente, a inibição da atividade da triptase foi capaz de reduzir amplamente a nocicepção e o edema induzidos pelo MSU. Coletivamente, nossos resultados demonstram que o MSU produz uma resposta nociceptiva e edematogênica mediada pela ativação do receptor TRPV1 e pela desgranulação de mastócitos.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaDorGotaMastócitoCapsaicinaTriptasePainGoutMast cellCapsaicinTryptaseCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAPapel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratosRole of TRPV1 on nociception and edema induced by monosodium urate crystals in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisFerreira, Julianohttp://lattes.cnpq.br/2694197910478313Schetinger, Maria Rosa Chitolinahttp://lattes.cnpq.br/4401319386725357Royes, Luiz Fernando Freirehttp://lattes.cnpq.br/0543081555633400http://lattes.cnpq.br/0998085530407594Hoffmeister, Carin Gorete Hendges20100000000040050050050050000296dee-06fe-4bc6-a73d-5a0cdd89e3bcc2de871c-b26e-4341-abeb-0a27237d24d4cba4a833-b1c5-4608-8453-7a46f671faf13844a51f-1f7f-46ca-93b7-18d1a9c07d2binfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALHOFFMEISTER, CARIN GORETE HENDGES.pdfapplication/pdf1061412http://repositorio.ufsm.br/bitstream/1/8949/1/HOFFMEISTER%2c%20CARIN%20GORETE%20HENDGES.pdf4aae16aa37c5f3874214b838e9475531MD51TEXTHOFFMEISTER, CARIN GORETE HENDGES.pdf.txtHOFFMEISTER, CARIN GORETE HENDGES.pdf.txtExtracted texttext/plain127525http://repositorio.ufsm.br/bitstream/1/8949/2/HOFFMEISTER%2c%20CARIN%20GORETE%20HENDGES.pdf.txt3b1908ddd8ff075b69813dcaf1361077MD52THUMBNAILHOFFMEISTER, CARIN GORETE HENDGES.pdf.jpgHOFFMEISTER, CARIN GORETE HENDGES.pdf.jpgIM Thumbnailimage/jpeg6052http://repositorio.ufsm.br/bitstream/1/8949/3/HOFFMEISTER%2c%20CARIN%20GORETE%20HENDGES.pdf.jpge8f0852500e3a4c929225ab89e3239bbMD531/89492022-09-06 14:21:16.018oai:repositorio.ufsm.br:1/8949Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-09-06T17:21:16Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
dc.title.alternative.eng.fl_str_mv |
Role of TRPV1 on nociception and edema induced by monosodium urate crystals in rats |
title |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
spellingShingle |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos Hoffmeister, Carin Gorete Hendges Dor Gota Mastócito Capsaicina Triptase Pain Gout Mast cell Capsaicin Tryptase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
title_full |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
title_fullStr |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
title_full_unstemmed |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
title_sort |
Papel do receptor TRPV1 na nocicepção e no edma induzido por cristais de urato monossódico em ratos |
author |
Hoffmeister, Carin Gorete Hendges |
author_facet |
Hoffmeister, Carin Gorete Hendges |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Ferreira, Juliano |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2694197910478313 |
dc.contributor.referee1.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4401319386725357 |
dc.contributor.referee2.fl_str_mv |
Royes, Luiz Fernando Freire |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0543081555633400 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0998085530407594 |
dc.contributor.author.fl_str_mv |
Hoffmeister, Carin Gorete Hendges |
contributor_str_mv |
Ferreira, Juliano Schetinger, Maria Rosa Chitolina Royes, Luiz Fernando Freire |
dc.subject.por.fl_str_mv |
Dor Gota Mastócito Capsaicina Triptase |
topic |
Dor Gota Mastócito Capsaicina Triptase Pain Gout Mast cell Capsaicin Tryptase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Pain Gout Mast cell Capsaicin Tryptase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (DE50=0.04 (0.01-0.11) mg/paw) and edema (DE50=0.08 (0.04-0.16) mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor antagonist SB366791 largely inhibited nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as the pretreatment with the tachykinin NK1 receptor antagonist RP 67580 also significantly reduced MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeat treatment with compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively inhibited nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin and tryptase in the injected tissue, confirming mast cell degranulation Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception, of MSU. Finally, the inhibition of tryptase activity was capable of largely reducing either MSU-induced nociception or edema. Collectively, the present findings demonstrate that MSU produces a nociceptive and edematogenic response mediated by TRPV1 receptor activation and mast cell degranulation. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-08-14 |
dc.date.accessioned.fl_str_mv |
2010-12-01 |
dc.date.available.fl_str_mv |
2010-12-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
HOFFMEISTER, Carin Gorete Hendges. Role of TRPV1 on nociception and edema induced by monosodium urate crystals in rats. 2009. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/8949 |
identifier_str_mv |
HOFFMEISTER, Carin Gorete Hendges. Role of TRPV1 on nociception and edema induced by monosodium urate crystals in rats. 2009. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
url |
http://repositorio.ufsm.br/handle/1/8949 |
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