Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular

Detalhes bibliográficos
Autor(a) principal: Carvalho, Maiara Simões
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/12600
Resumo: Introduction: The Interferential current (IC) is an electrotherapeutic modality widely used for analgesic purposes, however, few studies have sought to evaluate its mechanisms of action to promote the antinociceptive effect. The aim of this study was to investigate the involvement of spinal serotonergic and noradrenergic receptors in the antinociceptive effect of the interferential current in the animal model of articular inflammation in Wistar rats. Material and method: We included in this study 54 male Wistar rats distributed in the groups CI + saline, CI + DMSO 20%, inactive IC + saline, inactive IC + DMSO 20%, CI + methysergide, CI + tropanil dichlorobenzoate, CI + ioimbine, serotonin hydrochloride and hydrochloride of clonidine. At baseline, behavioral tests were performed for sensitivity and motor performance followed by induction of joint inflammation by injection of 3% carragein solution and 3% caolin in the left knee of the animals. After 24 h, the behavior was reevaluated followed by treatment with the current, preceded or not by pharmacological blockade. The pharmacological blockade was performed by means of intrathecal injection, applied before the treatment with the current. One hours after treatment with IC, the behavioral tests were repeated. The values of p < 0.05 were considered significant. Results: There was a significant decrease in the mechanical threshold of left paw withdrawal 24 h after the induction of inflammation in all groups (p < 0.0001). The groups treated with interferential current that received vehicles (saline or DMSO 20%) Significantly increased the mechanical threshold of paw withdrawal in comparison to the pre-treatment moment (p ≤ 0.001). Both with very large effect size according to Cohen's d (d = 1.95 and d = 1.83, respectively). There was blockade of the effect of IC in the groups that received, prior to the treatment with the current, the methysergide (non-selective antagonist of receptors 5-HT1 and 5-HT2) and tropanyl dichlorobenzoate (receptor antagonist 5-HT3). In these two groups, there was no statistically significant difference in the mechanical threshold of left paw withdrawal, when comparing the moments before and after treatment. In addition, after treatment, the pre-treated groups with methysergide or tropanyl dichlorobenzoate did not increase the mechanical threshold of left paw withdrawal, different from the vehicle groups. The animals that received yohimbine (α2-adrenergic antagonist) increased the mechanical threshold for the removal of the inflamed paw when comparing the pre-and post-treatment moments, showing that this pharmacological blockade did not prevent the effect of IC. Intrathecal injection of serotonergic and α2-adrenergic receptor agonists (serotonin hydrochloride and clonidine) significantly increased the mechanical threshold of left paw withdrawal (p ≤ 0.004). The distance traveled by the animals reduced significantly (p ≤ 0.0207) after the induction of inflammation, however, the administration of the drugs and/or treatment with IC did not exert influence on motor activity. Conclusion: This study shows part of the mechanism of action of IC in motor intensity to promote antinociceptive effect. This effect is mediated by spinal activation of 5-HT1, 5-HT2 and 5-HT3 receptors, but not α2-adrenergic receptors. These results allow professionals to justify the clinical indication of this electrotherapeutic resource, adapting its use to the physiopathological particularities of each individual.
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spelling Carvalho, Maiara SimõesSantana, Josimari Melo deReis, Kamilla Mayara Lucas da Cruz2020-01-21T12:42:37Z2020-01-21T12:42:37Z2019-10-08CARVALHO, Maiara Simões. Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular. 2019. 78 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2019.http://ri.ufs.br/jspui/handle/riufs/12600Introduction: The Interferential current (IC) is an electrotherapeutic modality widely used for analgesic purposes, however, few studies have sought to evaluate its mechanisms of action to promote the antinociceptive effect. The aim of this study was to investigate the involvement of spinal serotonergic and noradrenergic receptors in the antinociceptive effect of the interferential current in the animal model of articular inflammation in Wistar rats. Material and method: We included in this study 54 male Wistar rats distributed in the groups CI + saline, CI + DMSO 20%, inactive IC + saline, inactive IC + DMSO 20%, CI + methysergide, CI + tropanil dichlorobenzoate, CI + ioimbine, serotonin hydrochloride and hydrochloride of clonidine. At baseline, behavioral tests were performed for sensitivity and motor performance followed by induction of joint inflammation by injection of 3% carragein solution and 3% caolin in the left knee of the animals. After 24 h, the behavior was reevaluated followed by treatment with the current, preceded or not by pharmacological blockade. The pharmacological blockade was performed by means of intrathecal injection, applied before the treatment with the current. One hours after treatment with IC, the behavioral tests were repeated. The values of p < 0.05 were considered significant. Results: There was a significant decrease in the mechanical threshold of left paw withdrawal 24 h after the induction of inflammation in all groups (p < 0.0001). The groups treated with interferential current that received vehicles (saline or DMSO 20%) Significantly increased the mechanical threshold of paw withdrawal in comparison to the pre-treatment moment (p ≤ 0.001). Both with very large effect size according to Cohen's d (d = 1.95 and d = 1.83, respectively). There was blockade of the effect of IC in the groups that received, prior to the treatment with the current, the methysergide (non-selective antagonist of receptors 5-HT1 and 5-HT2) and tropanyl dichlorobenzoate (receptor antagonist 5-HT3). In these two groups, there was no statistically significant difference in the mechanical threshold of left paw withdrawal, when comparing the moments before and after treatment. In addition, after treatment, the pre-treated groups with methysergide or tropanyl dichlorobenzoate did not increase the mechanical threshold of left paw withdrawal, different from the vehicle groups. The animals that received yohimbine (α2-adrenergic antagonist) increased the mechanical threshold for the removal of the inflamed paw when comparing the pre-and post-treatment moments, showing that this pharmacological blockade did not prevent the effect of IC. Intrathecal injection of serotonergic and α2-adrenergic receptor agonists (serotonin hydrochloride and clonidine) significantly increased the mechanical threshold of left paw withdrawal (p ≤ 0.004). The distance traveled by the animals reduced significantly (p ≤ 0.0207) after the induction of inflammation, however, the administration of the drugs and/or treatment with IC did not exert influence on motor activity. Conclusion: This study shows part of the mechanism of action of IC in motor intensity to promote antinociceptive effect. This effect is mediated by spinal activation of 5-HT1, 5-HT2 and 5-HT3 receptors, but not α2-adrenergic receptors. These results allow professionals to justify the clinical indication of this electrotherapeutic resource, adapting its use to the physiopathological particularities of each individual.Introdução: A corrente interferencial (CI) é uma modalidade eletroterapêutica bastante utilizada para fins analgésicos, contudo, poucos estudos buscaram avaliar seus mecanismos de ação para promoção do efeito antinociceptivo. O objetivo deste estudo foi investigar a participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial no modelo animal de inflamação articular em ratos Wistar. Material e método: Foram incluídos neste estudo 54 ratos Wistar machos distribuídos nos grupos CI + salina, CI + DMSO 20%, CI inativa + salina, CI inativa + DMSO 20%, CI + metisergida, CI + tropanil diclorobenzoato, CI + ioimbina, cloridrato de serotonina e cloridrato de clonidina. No momento basal, foram realizados testes comportamentais para sensibilidade e desempenho motor seguido de indução de inflamação articular por injeção de solução de carragenina 3% e caolina 3% no joelho esquerdo dos animais. Após 24 h, o comportamento foi reavaliado seguido de tratamento com a corrente, antecedido ou não de bloqueio farmacológico. O bloqueio farmacológico foi realizado por meio de injeção intratecal, aplicada antes do tratamento com a corrente. Uma hora após o tratamento com a CI, os testes comportamentais foram repetidos. Os valores de p < 0,05 foram considerados significativos. Resultados: Houve diminuição significativa do limiar mecânico de retirada da pata esquerda 24 h após a indução da inflamação em todos os grupos (p < 0,0001). Os grupos tratados com corrente interferencial que receberam veículos (salina ou DMSO 20%) aumentaram significativamente o limiar mecânico de retirada da pata em comparação ao momento pré-tratamento (p ≤ 0,001). Ambos com tamanho de efeito muito grande de acordo com o d de Cohen (d = 1,95 e d = 1,83, respectivamente). Houve bloqueio do efeito da CI nos grupos que receberam, previamente ao tratamento com a corrente, a metisergida (antagonista não seletivo de receptores 5-HT1 e 5-HT2) e tropanil diclorobenzoato (antagonista de receptores 5-HT3). Nesses dois grupos, não houve diferença estatisticamente significante no limiar mecânico de retirada da pata esquerda, quando comparados os momentos pré e pós-tratamento. Além disso, no pós-tratamento, os grupos pré-tratados com metisergida ou tropanil diclorobenzoato não aumentaram o limiar mecânico de retirada da pata esquerda, diferente dos grupos veículos. Os animais que receberam ioimbina (antagonista α2-adrenérgico) aumentaram o limiar mecânico de retirada da pata inflamada quando comparados os momentos pré e pós-tratamento, mostrando que esse bloqueio farmacológico não impediu o efeito da CI. A injeção intratecal de agonistas de receptores serotoninérgicos e α2-adrenérgicos (cloridrato de serotonina e clonidina) aumentou significativamente o limiar mecânico de retirada da pata esquerda (p ≤ 0,004). A distância percorrida pelos animais reduziu significativamente (p ≤ 0,0207) após a indução da inflamação, contudo, a administração dos fármacos e/ou tratamento com a CI não exerceu influencia na atividade motora. Conclusão: Esse estudo mostra parte do mecanismo de ação da CI em intensidade motora para promoção de efeito antinociceptivo. Tal efeito é mediado por ativação espinal de receptores 5-HT1, 5-HT2 e 5-HT3, mas não de receptores α2-adrenérgicos. Esses resultados permitem aos profissionais justificar a indicação clínica desse recurso eletroterapêutico, adequando seu uso às particularidades fisiopatológicas de cada indivíduo.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESSão Cristóvão, SEporEletroterapiaMedição da dorReceptores de serotoninaReceptores de adrenalinaArticulaçõesInflamaçãoCorrente interferencialNocicepçãoReceptores serotoninérgicosReceptores adrenérgicosElectric stimulation therapyInterferential currentNociceptionAdrenergic receptorsSerotonin receptorsCIENCIAS BIOLOGICAS::FISIOLOGIAParticipação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articularInvolvement of serotonergic and noradrenergic spinal receptors in the antinociceptive effect of interferential current in an animal model of articular inflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Ciências FisiológicasUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/12600/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALMAIARA_SIMOES_CARVALHO.pdfMAIARA_SIMOES_CARVALHO.pdfapplication/pdf1496346https://ri.ufs.br/jspui/bitstream/riufs/12600/2/MAIARA_SIMOES_CARVALHO.pdfe141a9fd0da1f823a6e9bb3b72689d6fMD52TEXTMAIARA_SIMOES_CARVALHO.pdf.txtMAIARA_SIMOES_CARVALHO.pdf.txtExtracted texttext/plain173028https://ri.ufs.br/jspui/bitstream/riufs/12600/3/MAIARA_SIMOES_CARVALHO.pdf.txt555ff319d000e274c519ec472ab6f451MD53THUMBNAILMAIARA_SIMOES_CARVALHO.pdf.jpgMAIARA_SIMOES_CARVALHO.pdf.jpgGenerated Thumbnailimage/jpeg1300https://ri.ufs.br/jspui/bitstream/riufs/12600/4/MAIARA_SIMOES_CARVALHO.pdf.jpg211c66c1f76911866b5406e3355cb6caMD54riufs/126002020-01-21 09:42:43.122oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2020-01-21T12:42:43Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
dc.title.alternative.eng.fl_str_mv Involvement of serotonergic and noradrenergic spinal receptors in the antinociceptive effect of interferential current in an animal model of articular inflammation
title Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
spellingShingle Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
Carvalho, Maiara Simões
Eletroterapia
Medição da dor
Receptores de serotonina
Receptores de adrenalina
Articulações
Inflamação
Corrente interferencial
Nocicepção
Receptores serotoninérgicos
Receptores adrenérgicos
Electric stimulation therapy
Interferential current
Nociception
Adrenergic receptors
Serotonin receptors
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
title_full Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
title_fullStr Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
title_full_unstemmed Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
title_sort Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular
author Carvalho, Maiara Simões
author_facet Carvalho, Maiara Simões
author_role author
dc.contributor.author.fl_str_mv Carvalho, Maiara Simões
dc.contributor.advisor1.fl_str_mv Santana, Josimari Melo de
dc.contributor.advisor-co1.fl_str_mv Reis, Kamilla Mayara Lucas da Cruz
contributor_str_mv Santana, Josimari Melo de
Reis, Kamilla Mayara Lucas da Cruz
dc.subject.por.fl_str_mv Eletroterapia
Medição da dor
Receptores de serotonina
Receptores de adrenalina
Articulações
Inflamação
Corrente interferencial
Nocicepção
Receptores serotoninérgicos
Receptores adrenérgicos
topic Eletroterapia
Medição da dor
Receptores de serotonina
Receptores de adrenalina
Articulações
Inflamação
Corrente interferencial
Nocicepção
Receptores serotoninérgicos
Receptores adrenérgicos
Electric stimulation therapy
Interferential current
Nociception
Adrenergic receptors
Serotonin receptors
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Electric stimulation therapy
Interferential current
Nociception
Adrenergic receptors
Serotonin receptors
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description Introduction: The Interferential current (IC) is an electrotherapeutic modality widely used for analgesic purposes, however, few studies have sought to evaluate its mechanisms of action to promote the antinociceptive effect. The aim of this study was to investigate the involvement of spinal serotonergic and noradrenergic receptors in the antinociceptive effect of the interferential current in the animal model of articular inflammation in Wistar rats. Material and method: We included in this study 54 male Wistar rats distributed in the groups CI + saline, CI + DMSO 20%, inactive IC + saline, inactive IC + DMSO 20%, CI + methysergide, CI + tropanil dichlorobenzoate, CI + ioimbine, serotonin hydrochloride and hydrochloride of clonidine. At baseline, behavioral tests were performed for sensitivity and motor performance followed by induction of joint inflammation by injection of 3% carragein solution and 3% caolin in the left knee of the animals. After 24 h, the behavior was reevaluated followed by treatment with the current, preceded or not by pharmacological blockade. The pharmacological blockade was performed by means of intrathecal injection, applied before the treatment with the current. One hours after treatment with IC, the behavioral tests were repeated. The values of p < 0.05 were considered significant. Results: There was a significant decrease in the mechanical threshold of left paw withdrawal 24 h after the induction of inflammation in all groups (p < 0.0001). The groups treated with interferential current that received vehicles (saline or DMSO 20%) Significantly increased the mechanical threshold of paw withdrawal in comparison to the pre-treatment moment (p ≤ 0.001). Both with very large effect size according to Cohen's d (d = 1.95 and d = 1.83, respectively). There was blockade of the effect of IC in the groups that received, prior to the treatment with the current, the methysergide (non-selective antagonist of receptors 5-HT1 and 5-HT2) and tropanyl dichlorobenzoate (receptor antagonist 5-HT3). In these two groups, there was no statistically significant difference in the mechanical threshold of left paw withdrawal, when comparing the moments before and after treatment. In addition, after treatment, the pre-treated groups with methysergide or tropanyl dichlorobenzoate did not increase the mechanical threshold of left paw withdrawal, different from the vehicle groups. The animals that received yohimbine (α2-adrenergic antagonist) increased the mechanical threshold for the removal of the inflamed paw when comparing the pre-and post-treatment moments, showing that this pharmacological blockade did not prevent the effect of IC. Intrathecal injection of serotonergic and α2-adrenergic receptor agonists (serotonin hydrochloride and clonidine) significantly increased the mechanical threshold of left paw withdrawal (p ≤ 0.004). The distance traveled by the animals reduced significantly (p ≤ 0.0207) after the induction of inflammation, however, the administration of the drugs and/or treatment with IC did not exert influence on motor activity. Conclusion: This study shows part of the mechanism of action of IC in motor intensity to promote antinociceptive effect. This effect is mediated by spinal activation of 5-HT1, 5-HT2 and 5-HT3 receptors, but not α2-adrenergic receptors. These results allow professionals to justify the clinical indication of this electrotherapeutic resource, adapting its use to the physiopathological particularities of each individual.
publishDate 2019
dc.date.issued.fl_str_mv 2019-10-08
dc.date.accessioned.fl_str_mv 2020-01-21T12:42:37Z
dc.date.available.fl_str_mv 2020-01-21T12:42:37Z
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dc.identifier.citation.fl_str_mv CARVALHO, Maiara Simões. Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular. 2019. 78 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2019.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/12600
identifier_str_mv CARVALHO, Maiara Simões. Participação de receptores serotoninérgicos e noradrenérgicos espinais no efeito antinociceptivo da corrente interferencial em modelo animal de inflamação articular. 2019. 78 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2019.
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