Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/0013000005m8c |
Texto Completo: | http://repositorio.ufsm.br/handle/1/28415 |
Resumo: | Complex regional pain syndrome-type I (CRPS-I) affects upper or lower limbs distal parts, leading symptoms like chronic pain, edema, trophic changes and motor function abnormalities. This syndrome commonly follows factures and sprains. The pathophysiology of CRPS-I is not completely understood and its suggested that microvessels changes related to the syndrome maintenance lead to a reduction in oxygen supply. In this study the objective was to evaluation the time course of the antinociceptive activity of melatonin, an endogenous indolamine released mainly by pineal gland, in the mechanical and cold hypersensitivity and in the edema presented in the chronic post-ischemic pain (CPIP) in mice; an animal model of human CRPS-I, and participation of MT1/MT2 receptors and oxidative stress in this model. The antinociceptive activity of melatonin in the nociception evoked by TRPs (transient receptors potential) and ASICs (acid-sensing ion channels). CPIP was induced in Swiss male mice by placing a tourniquet proximal to the ankle joint for 3 hours, followed by removal to allow tissue reperfusion. The mechanical (0.4 g von Frey filaments) and cold (cold plate 4 ºC) hypersensitivity was mensured on second and seventh days after reperfusion. Catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) levels were measured 2 h, 2 and 7 days after reperfusion, tissues were collected 30 min after melatonin treatment (100 mg/kg, i.p.). Melatonin activity (10 – 100 mg/kg, i.p., or 10 – 100 ng/paw, i.pl.) was also evaluated by measuring of nociception evoked by TRPV1 agonists (capsaicin, 30,5 ng/paw, i.pl.), TRPA1 (cinnamaldehyde, 1,32 μg/paw), TRPM8 (menthol, 1.2 μg/paw) and ASICs (acetic acid 2%, pH 1.98). The treatment with melatonin (10-100 mg/kg, i.p.) dose-dependently reduced the mechanical hypersensitivity 2 and 7 days after reperfusion and with 100 mg/kg the effect remained by for up 2 h after administration. Furthermore, the treatment with melatonin (100 mg/kg, i.p.) also reduced the cold hypersensitivity 2 and 7 days after reperfusion. However, the melatonin effect (100 mg/kg) was not affected by pretreatment with luzindole (10 mg/kg, i.p., non-selective MT1/MT2 antagonist). The melatonin (100 mg/kg, i.p.) also reduced the edema evoked by CPIP in the second day after reperfusion. GR enzyme activity was reduced 2 h after reperfusion and melatonin treatment didn´t change this parameter. GR and GPx, and, Cat and GPx enzymes activities were elevated on days 2 and 7, respectively, and melatonin reversed this increase. The systemic administration (i.p.) of melatonin inhibited the nociception evoked by capsaicin, cinnamaldehyde, menthol and acid saline, inhibitions of 63 + 16%, 41 + 13%, 62 + 10% e 47 + 12%, respectively. Moreover, the peripheral administration of melatonin only inhibited the nociception evoked by capsaicin (49 + 6%) and cinnamaldehyde (60 + 6%). In conclusion, this study extends the literature and shows that melatonin is able to reduce the mechanical and thermal hypersensitivity and the edema in the CPIP model, probably by a modulation of redox status of the cell through its antioxidant properties and inhibition of peripheral nociceptors. |
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Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo IAntioxidant-analgesic effect of melatonin in a animal model of complex regional pain syndrome type ISíndrome de dor complexa regional tipo IDor crônica pós-isquemiaMelatoninaEstresse oxidativoEnzimas antioxidantesComplex regional pain syndrome-type IChronic post-ischemic painMelatoninOxidative stressAntioxidant enzymesCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAComplex regional pain syndrome-type I (CRPS-I) affects upper or lower limbs distal parts, leading symptoms like chronic pain, edema, trophic changes and motor function abnormalities. This syndrome commonly follows factures and sprains. The pathophysiology of CRPS-I is not completely understood and its suggested that microvessels changes related to the syndrome maintenance lead to a reduction in oxygen supply. In this study the objective was to evaluation the time course of the antinociceptive activity of melatonin, an endogenous indolamine released mainly by pineal gland, in the mechanical and cold hypersensitivity and in the edema presented in the chronic post-ischemic pain (CPIP) in mice; an animal model of human CRPS-I, and participation of MT1/MT2 receptors and oxidative stress in this model. The antinociceptive activity of melatonin in the nociception evoked by TRPs (transient receptors potential) and ASICs (acid-sensing ion channels). CPIP was induced in Swiss male mice by placing a tourniquet proximal to the ankle joint for 3 hours, followed by removal to allow tissue reperfusion. The mechanical (0.4 g von Frey filaments) and cold (cold plate 4 ºC) hypersensitivity was mensured on second and seventh days after reperfusion. Catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) levels were measured 2 h, 2 and 7 days after reperfusion, tissues were collected 30 min after melatonin treatment (100 mg/kg, i.p.). Melatonin activity (10 – 100 mg/kg, i.p., or 10 – 100 ng/paw, i.pl.) was also evaluated by measuring of nociception evoked by TRPV1 agonists (capsaicin, 30,5 ng/paw, i.pl.), TRPA1 (cinnamaldehyde, 1,32 μg/paw), TRPM8 (menthol, 1.2 μg/paw) and ASICs (acetic acid 2%, pH 1.98). The treatment with melatonin (10-100 mg/kg, i.p.) dose-dependently reduced the mechanical hypersensitivity 2 and 7 days after reperfusion and with 100 mg/kg the effect remained by for up 2 h after administration. Furthermore, the treatment with melatonin (100 mg/kg, i.p.) also reduced the cold hypersensitivity 2 and 7 days after reperfusion. However, the melatonin effect (100 mg/kg) was not affected by pretreatment with luzindole (10 mg/kg, i.p., non-selective MT1/MT2 antagonist). The melatonin (100 mg/kg, i.p.) also reduced the edema evoked by CPIP in the second day after reperfusion. GR enzyme activity was reduced 2 h after reperfusion and melatonin treatment didn´t change this parameter. GR and GPx, and, Cat and GPx enzymes activities were elevated on days 2 and 7, respectively, and melatonin reversed this increase. The systemic administration (i.p.) of melatonin inhibited the nociception evoked by capsaicin, cinnamaldehyde, menthol and acid saline, inhibitions of 63 + 16%, 41 + 13%, 62 + 10% e 47 + 12%, respectively. Moreover, the peripheral administration of melatonin only inhibited the nociception evoked by capsaicin (49 + 6%) and cinnamaldehyde (60 + 6%). In conclusion, this study extends the literature and shows that melatonin is able to reduce the mechanical and thermal hypersensitivity and the edema in the CPIP model, probably by a modulation of redox status of the cell through its antioxidant properties and inhibition of peripheral nociceptors.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA síndrome de dor complexa regional tipo I (SDCR-I) é uma patologia que atinge membros superiores ou inferiores de forma distal, levando a sintomas como dor crônica, edema, alterações tróficas e comprometimento motor. Esta síndrome geralmente tem início após lesões como fraturas e torções. A patofisiologia da SDCR-I ainda não é completamente entendida, porém, sugere-se que uma redução no aporte de oxigênio devido a alterações microvasculares esteja relacionada a manutenção da síndrome. O presente trabalho teve como objetivo avaliar a atividade antinociceptiva da melatonina, uma indolamina endógena liberada principalmente pela glândula pineal, na hipersensibilidade mecânica e térmica (ao frio) presente no modelo de dor crônica pós-isquemia (DCPI) em camundongos, o qual mimetiza os sinais e sintomas da SDCR-I em humanos, bem como a participação dos receptores MT1/MT2 e do estresse oxidativo neste efeito. A indução da DCPI em camundongos Suíços machos foi feita através do posicionamento de um torniquete próximo ao tornozelo dos animais, o qual foi mantido por 3 horas, seguido da remoção para permitir a reperfusão dos tecidos. A hipersensibilidade mecânica (através do filamento de Von Frey, 0,4 g) e térmica (placa fria, 4º C) e o edema da pata foram avaliados no segundo e no sétimo dia após a reperfusão. Além disto, foi analisada a atividade das enzimas catalase (CAT), glutationa redutase (GR) e glutationa peroxidase (GPx) e a imunorreatividade ao aduto malondialdeído-preteína (MDA) 2 h, 2 e 7 dias após a reperfusão, sendo que os tecidos foram coletados 30 min após o tratamento com melatonina (100 mg/kg, i.p.). O efeito da melatonina (10 – 100 mg/kg, i.p., ou 10 – 100 ng/pata, i.pl.) também foi avaliada frente à nocicepção espontânea evocada por agonistas de TRPV1 (capsaicina 30,5 ng/pata), TRPA1 (cinamaldeído 1,32 μg/pata), TRPM8 (mentol 187,5 μg/pata) e ASICs (salina acidificada, pH 1,98). A melatonina (10-100 mg/kg, i.p.) reduziu de forma dependente da dose a hipersensibilidade mecânica no segundo e no sétimo dia após a reperfusão, sendo que na dose de 100 mg/kg seu efeito persistiu por até 2 horas após a administração. Além disto, a melatonina (100 mg/kg, i.p.) também reduziu a hipersensibilidade térmica (ao frio) no segundo e no sétimo dia após a reperfusão. Contudo, o efeito da melatonina (100 mg/kg, i.p.) na hipersensibilidade mecânica e térmica (placa fria) não foi alterada pela administração prévia de luzindol (10 mg/kg, i.p., antagonista não-seletivo de receptores MT1/MT2). O tratamento com melatonina (100 mg/kg, i.p.) também reverteu o edema gerado pela indução de DCPI. A atividade da enzima GR se apresentou reduzida 2 h após a reperfusão, e o tratamento com melatonina não alterou esse parâmetro. A atividade das enzimas GR e GPx, e CAT e GPx, se apresentou aumentada no segundo e no sétimo dia, respectivamente, sendo que o tratamento com melatonina reverteu este aumento. A administração sistêmica de melatonina (via i.p.) foi capaz de inibir a nocicepção evocada pela capsaicina, cinamaldeído, mentol e salina acidificada, com inibição de 63 + 16%, 41 + 13%, 62 + 10% e 47 + 12%, respectivamente. Além disto, a administração periférica da melatonina (via i.pl.) inibiu somente a resposta evocada pela capsaicina (49 + 6%) e cinamaldeído (60 + 6%). Em conclusão este estudo estendeu os dados da literatura demonstrando que a melatonina foi capaz de reduzir a hipersensibilidade mecânica e térmica (ao frio) e o edema provocados pela indução do modelo de DCPI em camundongos. O seu mecanismo de ação não está completamente elucidado, contudo, o efeito da melatonina provavelmente depende da sua ação antioxidante através da modulação do estado redox da célula e por consequência da atividade das enzimas antioxidantes, podendo também estar atuando através da inibição da transmissão nociceptiva por inibir a ativação de nociceptores periféricos, em especial dos TRPV1 e TRPA1.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeSantos, Adair Roberto Soares doshttp://lattes.cnpq.br/9263042062534666Mello, Carlos Fernando deNascimento, Francisney Pinto doFurian, Ana FláviaMack, Josiel Mileno2023-03-27T14:36:23Z2023-03-27T14:36:23Z2013-02-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/28415ark:/26339/0013000005m8cporAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-03-27T14:36:23Zoai:repositorio.ufsm.br:1/28415Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2024-07-29T10:25:03.155721Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I Antioxidant-analgesic effect of melatonin in a animal model of complex regional pain syndrome type I |
title |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
spellingShingle |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I Mack, Josiel Mileno Síndrome de dor complexa regional tipo I Dor crônica pós-isquemia Melatonina Estresse oxidativo Enzimas antioxidantes Complex regional pain syndrome-type I Chronic post-ischemic pain Melatonin Oxidative stress Antioxidant enzymes CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
title_full |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
title_fullStr |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
title_full_unstemmed |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
title_sort |
Efeito analgésico da melatonina em um modelo animal da síndrome de dor complexa regional tipo I |
author |
Mack, Josiel Mileno |
author_facet |
Mack, Josiel Mileno |
author_role |
author |
dc.contributor.none.fl_str_mv |
Santos, Adair Roberto Soares dos http://lattes.cnpq.br/9263042062534666 Mello, Carlos Fernando de Nascimento, Francisney Pinto do Furian, Ana Flávia |
dc.contributor.author.fl_str_mv |
Mack, Josiel Mileno |
dc.subject.por.fl_str_mv |
Síndrome de dor complexa regional tipo I Dor crônica pós-isquemia Melatonina Estresse oxidativo Enzimas antioxidantes Complex regional pain syndrome-type I Chronic post-ischemic pain Melatonin Oxidative stress Antioxidant enzymes CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Síndrome de dor complexa regional tipo I Dor crônica pós-isquemia Melatonina Estresse oxidativo Enzimas antioxidantes Complex regional pain syndrome-type I Chronic post-ischemic pain Melatonin Oxidative stress Antioxidant enzymes CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Complex regional pain syndrome-type I (CRPS-I) affects upper or lower limbs distal parts, leading symptoms like chronic pain, edema, trophic changes and motor function abnormalities. This syndrome commonly follows factures and sprains. The pathophysiology of CRPS-I is not completely understood and its suggested that microvessels changes related to the syndrome maintenance lead to a reduction in oxygen supply. In this study the objective was to evaluation the time course of the antinociceptive activity of melatonin, an endogenous indolamine released mainly by pineal gland, in the mechanical and cold hypersensitivity and in the edema presented in the chronic post-ischemic pain (CPIP) in mice; an animal model of human CRPS-I, and participation of MT1/MT2 receptors and oxidative stress in this model. The antinociceptive activity of melatonin in the nociception evoked by TRPs (transient receptors potential) and ASICs (acid-sensing ion channels). CPIP was induced in Swiss male mice by placing a tourniquet proximal to the ankle joint for 3 hours, followed by removal to allow tissue reperfusion. The mechanical (0.4 g von Frey filaments) and cold (cold plate 4 ºC) hypersensitivity was mensured on second and seventh days after reperfusion. Catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) levels were measured 2 h, 2 and 7 days after reperfusion, tissues were collected 30 min after melatonin treatment (100 mg/kg, i.p.). Melatonin activity (10 – 100 mg/kg, i.p., or 10 – 100 ng/paw, i.pl.) was also evaluated by measuring of nociception evoked by TRPV1 agonists (capsaicin, 30,5 ng/paw, i.pl.), TRPA1 (cinnamaldehyde, 1,32 μg/paw), TRPM8 (menthol, 1.2 μg/paw) and ASICs (acetic acid 2%, pH 1.98). The treatment with melatonin (10-100 mg/kg, i.p.) dose-dependently reduced the mechanical hypersensitivity 2 and 7 days after reperfusion and with 100 mg/kg the effect remained by for up 2 h after administration. Furthermore, the treatment with melatonin (100 mg/kg, i.p.) also reduced the cold hypersensitivity 2 and 7 days after reperfusion. However, the melatonin effect (100 mg/kg) was not affected by pretreatment with luzindole (10 mg/kg, i.p., non-selective MT1/MT2 antagonist). The melatonin (100 mg/kg, i.p.) also reduced the edema evoked by CPIP in the second day after reperfusion. GR enzyme activity was reduced 2 h after reperfusion and melatonin treatment didn´t change this parameter. GR and GPx, and, Cat and GPx enzymes activities were elevated on days 2 and 7, respectively, and melatonin reversed this increase. The systemic administration (i.p.) of melatonin inhibited the nociception evoked by capsaicin, cinnamaldehyde, menthol and acid saline, inhibitions of 63 + 16%, 41 + 13%, 62 + 10% e 47 + 12%, respectively. Moreover, the peripheral administration of melatonin only inhibited the nociception evoked by capsaicin (49 + 6%) and cinnamaldehyde (60 + 6%). In conclusion, this study extends the literature and shows that melatonin is able to reduce the mechanical and thermal hypersensitivity and the edema in the CPIP model, probably by a modulation of redox status of the cell through its antioxidant properties and inhibition of peripheral nociceptors. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-02-18 2023-03-27T14:36:23Z 2023-03-27T14:36:23Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/28415 |
dc.identifier.dark.fl_str_mv |
ark:/26339/0013000005m8c |
url |
http://repositorio.ufsm.br/handle/1/28415 |
identifier_str_mv |
ark:/26339/0013000005m8c |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1814439735583571968 |