Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study

Detalhes bibliográficos
Autor(a) principal: Deitos, Alícia
Data de Publicação: 2018
Outros Autores: Soldatelli, Matheus Dorigatti, Sarria, Jairo Alberto Dussán, Souza, Andressa de, Torres, Iraci Lucena da Silva, Fregni, Felipe, Caumo, Wolnei
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/188505
Resumo: The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes. Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication. Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; 57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, 26 to 46.00) and the placebo increased it by 19.56% (CI 95%; 8.10 to 59.45; P = 0.02). Pregabalin also improved the pain measures. In the treatment group, the BDNF-adjusted index was positively correlated and the serum S100-B negatively correlated with the CSP, respectively. However, in the HS, pregabalin and the placebo did not induce a statistically significant effect in either intracortical excitability or pain measures. Conclusion: These results suggest that pregabalin’s effect on cortical neural networks occurs, particularly under basal neuronal hyperexcitability, because its impact on the cortical excitability and the pain measures was observed only in the FM group. This indicates that pregabalin increased the CSP to induce inhibition in specific neural networks, while it increased the SICI to improve the excitability in other neurobiological systems. Trial registration in clinicaltrials.gov Identifier: NCT02639533.
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spelling Deitos, AlíciaSoldatelli, Matheus DorigattiSarria, Jairo Alberto DussánSouza, Andressa deTorres, Iraci Lucena da SilvaFregni, FelipeCaumo, Wolnei2019-02-02T02:31:25Z20181662-5161http://hdl.handle.net/10183/188505001083249The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes. Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication. Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; 57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, 26 to 46.00) and the placebo increased it by 19.56% (CI 95%; 8.10 to 59.45; P = 0.02). Pregabalin also improved the pain measures. In the treatment group, the BDNF-adjusted index was positively correlated and the serum S100-B negatively correlated with the CSP, respectively. However, in the HS, pregabalin and the placebo did not induce a statistically significant effect in either intracortical excitability or pain measures. Conclusion: These results suggest that pregabalin’s effect on cortical neural networks occurs, particularly under basal neuronal hyperexcitability, because its impact on the cortical excitability and the pain measures was observed only in the FM group. This indicates that pregabalin increased the CSP to induce inhibition in specific neural networks, while it increased the SICI to improve the excitability in other neurobiological systems. Trial registration in clinicaltrials.gov Identifier: NCT02639533.application/pdfengFrontiers in human neuroscience. Lousanne. Vol. 12 (Nov. 2018), article 406, 14 p.FibromialgiaPregabalinaFator neurotrófico derivado do encéfaloProteínas S100FibromyalgiaCortical silent periodShort intracortical inhibitionBDNFS100BNovel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover studyEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001083249.pdf.txt001083249.pdf.txtExtracted Texttext/plain68521http://www.lume.ufrgs.br/bitstream/10183/188505/2/001083249.pdf.txt01e336a43dee7a3d746be2e80e427bbeMD52ORIGINAL001083249.pdfTexto completo (inglês)application/pdf2319342http://www.lume.ufrgs.br/bitstream/10183/188505/1/001083249.pdfcfa4d2d186a0774c6f3b4c1e493cef3bMD5110183/1885052019-02-03 02:31:54.716644oai:www.lume.ufrgs.br:10183/188505Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2019-02-03T04:31:54Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
title Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
spellingShingle Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
Deitos, Alícia
Fibromialgia
Pregabalina
Fator neurotrófico derivado do encéfalo
Proteínas S100
Fibromyalgia
Cortical silent period
Short intracortical inhibition
BDNF
S100B
title_short Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
title_full Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
title_fullStr Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
title_full_unstemmed Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
title_sort Novel insights of effects of pregabalin on neural mechanisms of intracortical disinhibition in physiopathology of fibromyalgia : an explanatory, randomized, double-blind crossover study
author Deitos, Alícia
author_facet Deitos, Alícia
Soldatelli, Matheus Dorigatti
Sarria, Jairo Alberto Dussán
Souza, Andressa de
Torres, Iraci Lucena da Silva
Fregni, Felipe
Caumo, Wolnei
author_role author
author2 Soldatelli, Matheus Dorigatti
Sarria, Jairo Alberto Dussán
Souza, Andressa de
Torres, Iraci Lucena da Silva
Fregni, Felipe
Caumo, Wolnei
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Deitos, Alícia
Soldatelli, Matheus Dorigatti
Sarria, Jairo Alberto Dussán
Souza, Andressa de
Torres, Iraci Lucena da Silva
Fregni, Felipe
Caumo, Wolnei
dc.subject.por.fl_str_mv Fibromialgia
Pregabalina
Fator neurotrófico derivado do encéfalo
Proteínas S100
topic Fibromialgia
Pregabalina
Fator neurotrófico derivado do encéfalo
Proteínas S100
Fibromyalgia
Cortical silent period
Short intracortical inhibition
BDNF
S100B
dc.subject.eng.fl_str_mv Fibromyalgia
Cortical silent period
Short intracortical inhibition
BDNF
S100B
description The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes. Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication. Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; 57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, 26 to 46.00) and the placebo increased it by 19.56% (CI 95%; 8.10 to 59.45; P = 0.02). Pregabalin also improved the pain measures. In the treatment group, the BDNF-adjusted index was positively correlated and the serum S100-B negatively correlated with the CSP, respectively. However, in the HS, pregabalin and the placebo did not induce a statistically significant effect in either intracortical excitability or pain measures. Conclusion: These results suggest that pregabalin’s effect on cortical neural networks occurs, particularly under basal neuronal hyperexcitability, because its impact on the cortical excitability and the pain measures was observed only in the FM group. This indicates that pregabalin increased the CSP to induce inhibition in specific neural networks, while it increased the SICI to improve the excitability in other neurobiological systems. Trial registration in clinicaltrials.gov Identifier: NCT02639533.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2019-02-02T02:31:25Z
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dc.relation.ispartof.pt_BR.fl_str_mv Frontiers in human neuroscience. Lousanne. Vol. 12 (Nov. 2018), article 406, 14 p.
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