Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Oliveira, Larissa Resende
Orientador(a): Santana, Josimari Melo de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Pós-Graduação em Ciências Fisiológicas
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://ri.ufs.br/jspui/handle/riufs/12591
Resumo: Chronic muscle widespread pain (CMWP) is a public health problem with high social and economic burden and appears to be related with changes in the functioning of cortical areas of the central nervous system. Physical activity, if practiced regularly, can benefit people with CMWP, and possibly prevent its development. Thus, the present study aimed to evaluate the effect of regular physical activity on the treatment and prevention of hyperalgesia on an animal model of CMWP as well as on the expression of cortical neurons. Seventy-nine male and female C57BL/6 mice (25-30 g) were housed separately in their home cages with free access to the running wheel, water and food (physically active animals) or only with water and food (sedentary animals). For induction of CMWP, animals received two intramuscular injections of pH 4.0 saline solution. We tested the mechanical hyperalgesia of the gastrocnemius muscle (Tweezer), and of the paw (von Frey filaments). The experimental design was divided into 4 protocols, with their respective groups: 1) 2 weeks of physical activity after induction of hyperalgesia, with groups of physically active animals (n = 8) and sedentary animals (n = 8) ); 2) 2 weeks of physical activity prior to induction of hyperalgesia, with healthy and physically active animals (AFP2) (n = 8) and the healthy and sedentary group (SDP2) (n = 8); 3) 2 weeks of physical activity after induction of hyperalgesia + additional exercise, with the group of animals physically active (AFT + EA) (n = 8) and sedentary animals (SDT + EA) (n = 8) and 4 weeks of physical activity before the induction of hyperalgesia, with the healthy and physically active group (AFP4) (n = 14) and healthy and sedentary (SDP4) (n = 14). Behavioral tests were performed at the following times: before and after induction of hyperalgesia, and after 48h, 96h, 1 week and 2 weeks of exercise (for protocols 1 and 2) and before and after 2 or 4 weeks of exercise, and during 1 week post exercise (for protocols 3 and 4). In order to evaluate the mechanisms of action of the exercise in the prevention of hyperalgesia, double immunofluorescence for cAMP (CREB) and phosphorylated CREB response element (pCREB) was used to label neurons in the following cerebral areas: anterior cingulate cortex ), insular cortex (IC), and central amygdala (ACe). The results showed that 2 weeks of voluntary physical activity or 2 weeks of voluntary physical activity + additional exercise did not revert the primary or secondary hyperalgesia of the CMWP model. However, 2 or 4 weeks of voluntary physical activity significantly prevented the increase of paw responses (bilateral hyperalgesia) bilaterally (p<0.05) in the animals of the AFP2 and AFP4 groups, and maintained this response by up to 4 (AFP2) or 5 Day (AFP4) after model induction (p<0.05), compared to the groups (SDP2) and (SDP4), respectively. In addition, a number of neurons were positively labeled for CREB and pCREB significantly lower in the AFP4 group when compared to the SDP4 group, in the following captured areas: CCA (p<0.0001), CI (p<0.0001), and ACe (p = 0.0007). Our findings indicate that short-term physical activity is not effective in the treatment of CMWP. However, regular physical activity is effective to prevent the increase of hyperalgesia, showing that physical inactivity is a risk factor for its development, and that changes in the sensory cortical neurons activity may be, at least in part, responsible for these results.
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spelling Oliveira, Larissa ResendeSantana, Josimari Melo de2020-01-20T19:19:30Z2020-01-20T19:19:30Z2017-08-09OLIVEIRA, Larissa Resende. Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos. 2017. 67 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2017.http://ri.ufs.br/jspui/handle/riufs/12591Chronic muscle widespread pain (CMWP) is a public health problem with high social and economic burden and appears to be related with changes in the functioning of cortical areas of the central nervous system. Physical activity, if practiced regularly, can benefit people with CMWP, and possibly prevent its development. Thus, the present study aimed to evaluate the effect of regular physical activity on the treatment and prevention of hyperalgesia on an animal model of CMWP as well as on the expression of cortical neurons. Seventy-nine male and female C57BL/6 mice (25-30 g) were housed separately in their home cages with free access to the running wheel, water and food (physically active animals) or only with water and food (sedentary animals). For induction of CMWP, animals received two intramuscular injections of pH 4.0 saline solution. We tested the mechanical hyperalgesia of the gastrocnemius muscle (Tweezer), and of the paw (von Frey filaments). The experimental design was divided into 4 protocols, with their respective groups: 1) 2 weeks of physical activity after induction of hyperalgesia, with groups of physically active animals (n = 8) and sedentary animals (n = 8) ); 2) 2 weeks of physical activity prior to induction of hyperalgesia, with healthy and physically active animals (AFP2) (n = 8) and the healthy and sedentary group (SDP2) (n = 8); 3) 2 weeks of physical activity after induction of hyperalgesia + additional exercise, with the group of animals physically active (AFT + EA) (n = 8) and sedentary animals (SDT + EA) (n = 8) and 4 weeks of physical activity before the induction of hyperalgesia, with the healthy and physically active group (AFP4) (n = 14) and healthy and sedentary (SDP4) (n = 14). Behavioral tests were performed at the following times: before and after induction of hyperalgesia, and after 48h, 96h, 1 week and 2 weeks of exercise (for protocols 1 and 2) and before and after 2 or 4 weeks of exercise, and during 1 week post exercise (for protocols 3 and 4). In order to evaluate the mechanisms of action of the exercise in the prevention of hyperalgesia, double immunofluorescence for cAMP (CREB) and phosphorylated CREB response element (pCREB) was used to label neurons in the following cerebral areas: anterior cingulate cortex ), insular cortex (IC), and central amygdala (ACe). The results showed that 2 weeks of voluntary physical activity or 2 weeks of voluntary physical activity + additional exercise did not revert the primary or secondary hyperalgesia of the CMWP model. However, 2 or 4 weeks of voluntary physical activity significantly prevented the increase of paw responses (bilateral hyperalgesia) bilaterally (p<0.05) in the animals of the AFP2 and AFP4 groups, and maintained this response by up to 4 (AFP2) or 5 Day (AFP4) after model induction (p<0.05), compared to the groups (SDP2) and (SDP4), respectively. In addition, a number of neurons were positively labeled for CREB and pCREB significantly lower in the AFP4 group when compared to the SDP4 group, in the following captured areas: CCA (p<0.0001), CI (p<0.0001), and ACe (p = 0.0007). Our findings indicate that short-term physical activity is not effective in the treatment of CMWP. However, regular physical activity is effective to prevent the increase of hyperalgesia, showing that physical inactivity is a risk factor for its development, and that changes in the sensory cortical neurons activity may be, at least in part, responsible for these results.A dor muscular crônica difusa (DMCD) é um problema de saúde pública com alto ônus social e econômico e parece estar relacionada com alterações do funcionamento de áreas corticais do sistema nervoso central. A atividade física, se praticada regularmente, pode beneficiar pessoas com DMCD, e possivelmente prevenir o desenvolvimento desta. Sendo assim, o objetivo do presente estudo foi investigar os efeitos da atividade física regular no tratamento e na prevenção da hiperalgesia no modelo animal de DMCD, bem como na expressão de neurônios corticais. Setenta e nove camundongos machos e fêmeas da espécie C57BL/6 (25-30 g) ficaram alocados separadamente em caixas com livre acesso à roda de corrida, água e comida (animais fisicamente ativos) ou somente com água e comida (animais sedentários). Para indução da DMCD, os animais receberam duas injeções intramusculares de solução salina pH 4,0. Foi avaliada a hiperalgesia mecânica primária no músculo gastrocnêmio (Tweezer) e secundária, na pata (filamentos de von Frey). O delineamento experimental foi dividido em quatro protocolos, com seus respectivos grupos: 1) 2 semanas de atividade física após indução da hiperalgesia, com os grupos de animais fisicamente ativos (AFT) (n=8) e sedentários (SDT) (n=8); 2) 2 semanas de atividade física após indução da hiperalgesia + exercício adicional, com o grupo de animais fisicamente ativos (AFT+EA) (n=8) e animais sedentários (SDT+EA) (n=8); 3) 2 semanas de atividade física antes da indução da hiperalgesia, com o grupo de animais saudáveis e fisicamente ativos (AFP2) (n=7) e o grupo saudáveis e sedentários (SDP2) (n=7) e 4) 4 semanas de atividade física antes da indução da hiperalgesia, com o grupo saudáveis e fisicamente ativos (AFP4) (n=14) e saudáveis e sedentários (SDP4) (n=14). Os testes comportamentais foram realizados nos seguintes tempos: antes e após indução da hiperalgesia, e após 48 h, 96 h, 1 semana e 2 semanas de exercício (para os protocolos 1 e 2) e antes e depois de 2 ou 4 semanas de exercício, e durante 1 semana pós-exercício (para os protocolos 3 e 4). Para avaliar os mecanismos de ação do exercício na prevenção da hiperalgesia, foi realizada dupla imunofluorescência para proteína ligante ao elemento de resposta ao cAMP (CREB) e CREB fosforilado (pCREB), para marcação de neurônios nas seguintes áreas cerebrais: córtex cingulado anterior (CCA), córtex insular (CI), e amigdala (ACe). Os resultados mostraram que 2 semanas de atividade física voluntária ou 2 semanas de atividade física voluntária + exercício adicional não reverteram a hiperalgesia primária e secundária em modelo de DMCD. Porém, 2 ou 4 semanas de atividade física voluntária preveniu significativamente o aumento das respostas da pata (hiperalgesia secundaria) bilateralmente (p<0,05) nos animais dos grupos AFP2 e AFP4, e manteve esta resposta por até 4 (AFP2) ou 5 dias (AFP4) após a indução do modelo (p<0,05), comparado com os grupos (SDP2) e (SDP4), respectivamente. Ademais, foi observado um número de neurônios marcados positivamente para CREB e pCREB significativamente menor no grupo AFP4, quando comparado ao grupo SDP4, nas seguintes áreas capturadas: CCA (p<0,0001), CI (p<0,0001), e ACe (p=0,0007). Nossos achados indicam que atividade física de curta duração não é efetiva no tratamento da DMCD. Porém, atividade física regular é efetiva para prevenir o aumento da hiperalgesia, mostrando que a inatividade física é um fator de risco para o desenvolvimento da mesma e, ainda, que mudanças na atividade de neurônios corticais sensoriais podem ser, pelo menos em parte, responsáveis por essas respostas.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESSão Cristóvão, SEporFibromialgiaDor crônicaHiperalgesiaCórtex cerebralExercícios físicosFibromyalgiaChronic painHyperalgesiaExerciseCerebral córtexCIENCIAS BIOLOGICAS::FISIOLOGIAEfeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongosEffects of regular physical activity on animal model of chronic muscle widespread pain (CMWP) and on activation of cortical neurons in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências FisiológicasUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessORIGINALLARISSA_RESENDE_OLIVEIRA.pdfLARISSA_RESENDE_OLIVEIRA.pdfapplication/pdf1501464https://ri.ufs.br/jspui/bitstream/riufs/12591/2/LARISSA_RESENDE_OLIVEIRA.pdf858888a810a561d276e06abac7a2b11cMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/12591/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51TEXTLARISSA_RESENDE_OLIVEIRA.pdf.txtLARISSA_RESENDE_OLIVEIRA.pdf.txtExtracted texttext/plain152359https://ri.ufs.br/jspui/bitstream/riufs/12591/3/LARISSA_RESENDE_OLIVEIRA.pdf.txt711821bfa766337d3d9f6064e009aac4MD53THUMBNAILLARISSA_RESENDE_OLIVEIRA.pdf.jpgLARISSA_RESENDE_OLIVEIRA.pdf.jpgGenerated Thumbnailimage/jpeg1244https://ri.ufs.br/jspui/bitstream/riufs/12591/4/LARISSA_RESENDE_OLIVEIRA.pdf.jpg85020cf8a4bca736bade90f339ab8936MD54riufs/125912020-01-20 16:19:30.964oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2020-01-20T19:19:30Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
dc.title.alternative.eng.fl_str_mv Effects of regular physical activity on animal model of chronic muscle widespread pain (CMWP) and on activation of cortical neurons in mice
title Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
spellingShingle Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
Oliveira, Larissa Resende
Fibromialgia
Dor crônica
Hiperalgesia
Córtex cerebral
Exercícios físicos
Fibromyalgia
Chronic pain
Hyperalgesia
Exercise
Cerebral córtex
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
title_full Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
title_fullStr Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
title_full_unstemmed Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
title_sort Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos
author Oliveira, Larissa Resende
author_facet Oliveira, Larissa Resende
author_role author
dc.contributor.author.fl_str_mv Oliveira, Larissa Resende
dc.contributor.advisor1.fl_str_mv Santana, Josimari Melo de
contributor_str_mv Santana, Josimari Melo de
dc.subject.por.fl_str_mv Fibromialgia
Dor crônica
Hiperalgesia
Córtex cerebral
Exercícios físicos
topic Fibromialgia
Dor crônica
Hiperalgesia
Córtex cerebral
Exercícios físicos
Fibromyalgia
Chronic pain
Hyperalgesia
Exercise
Cerebral córtex
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Fibromyalgia
Chronic pain
Hyperalgesia
Exercise
Cerebral córtex
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description Chronic muscle widespread pain (CMWP) is a public health problem with high social and economic burden and appears to be related with changes in the functioning of cortical areas of the central nervous system. Physical activity, if practiced regularly, can benefit people with CMWP, and possibly prevent its development. Thus, the present study aimed to evaluate the effect of regular physical activity on the treatment and prevention of hyperalgesia on an animal model of CMWP as well as on the expression of cortical neurons. Seventy-nine male and female C57BL/6 mice (25-30 g) were housed separately in their home cages with free access to the running wheel, water and food (physically active animals) or only with water and food (sedentary animals). For induction of CMWP, animals received two intramuscular injections of pH 4.0 saline solution. We tested the mechanical hyperalgesia of the gastrocnemius muscle (Tweezer), and of the paw (von Frey filaments). The experimental design was divided into 4 protocols, with their respective groups: 1) 2 weeks of physical activity after induction of hyperalgesia, with groups of physically active animals (n = 8) and sedentary animals (n = 8) ); 2) 2 weeks of physical activity prior to induction of hyperalgesia, with healthy and physically active animals (AFP2) (n = 8) and the healthy and sedentary group (SDP2) (n = 8); 3) 2 weeks of physical activity after induction of hyperalgesia + additional exercise, with the group of animals physically active (AFT + EA) (n = 8) and sedentary animals (SDT + EA) (n = 8) and 4 weeks of physical activity before the induction of hyperalgesia, with the healthy and physically active group (AFP4) (n = 14) and healthy and sedentary (SDP4) (n = 14). Behavioral tests were performed at the following times: before and after induction of hyperalgesia, and after 48h, 96h, 1 week and 2 weeks of exercise (for protocols 1 and 2) and before and after 2 or 4 weeks of exercise, and during 1 week post exercise (for protocols 3 and 4). In order to evaluate the mechanisms of action of the exercise in the prevention of hyperalgesia, double immunofluorescence for cAMP (CREB) and phosphorylated CREB response element (pCREB) was used to label neurons in the following cerebral areas: anterior cingulate cortex ), insular cortex (IC), and central amygdala (ACe). The results showed that 2 weeks of voluntary physical activity or 2 weeks of voluntary physical activity + additional exercise did not revert the primary or secondary hyperalgesia of the CMWP model. However, 2 or 4 weeks of voluntary physical activity significantly prevented the increase of paw responses (bilateral hyperalgesia) bilaterally (p<0.05) in the animals of the AFP2 and AFP4 groups, and maintained this response by up to 4 (AFP2) or 5 Day (AFP4) after model induction (p<0.05), compared to the groups (SDP2) and (SDP4), respectively. In addition, a number of neurons were positively labeled for CREB and pCREB significantly lower in the AFP4 group when compared to the SDP4 group, in the following captured areas: CCA (p<0.0001), CI (p<0.0001), and ACe (p = 0.0007). Our findings indicate that short-term physical activity is not effective in the treatment of CMWP. However, regular physical activity is effective to prevent the increase of hyperalgesia, showing that physical inactivity is a risk factor for its development, and that changes in the sensory cortical neurons activity may be, at least in part, responsible for these results.
publishDate 2017
dc.date.issued.fl_str_mv 2017-08-09
dc.date.accessioned.fl_str_mv 2020-01-20T19:19:30Z
dc.date.available.fl_str_mv 2020-01-20T19:19:30Z
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dc.identifier.citation.fl_str_mv OLIVEIRA, Larissa Resende. Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos. 2017. 67 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2017.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/12591
identifier_str_mv OLIVEIRA, Larissa Resende. Efeitos da atividade física regular no modelo animal de dor muscular crônica difusa e na ativação de neurônios corticais e da amigdala em camundongos. 2017. 67 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2017.
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repository.name.fl_str_mv Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)
repository.mail.fl_str_mv repositorio@academico.ufs.br
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