Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial
Associação de baixa dose de naltrexona e estimulação transcraniana por corrente contínua na fibromialgia: um ensaio clínico randomizado, duplo-cego, paralelo
Tânia Maria Hendges de Paula, Mariane Schäffer Castro, Liciane Fernandes Medeiros, Rodrigo Hernandes Paludo, Fabricia Fritz Couto, Tainá Ramires da Costa, Juliana Pereira Fortes, Maiara de Oliveira Salbego, Gabriel Schardosim Behnck, Thielly Amaral Mesquita de Moura, Mariana Lenz Tarouco, Wolnei Caumo, Andressa de Souza
Abstract
Introduction
Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management.
Objective
The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia.
Methods
This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels.
Results
At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p = 0.001), and placebo+tDCS Sham (p = 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p = 0.001), effect of pain on activities (p = 0.014) and emotions (p = 0.008). Depressive symptoms reduced after all active interventions (p > 0.001).
Conclusion
Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.
Keywords
Resumo
Introdução
A fibromialgia é uma dor musculoesquelética crônica complexa, generalizada e difusa. Abordagens farmacológicas são amplamente utilizadas para aliviar a dor e aumentar a qualidade de vida. Foi demonstrado que a naltrexona em baixa dose (NBD) aumenta o limiar nociceptivo em pacientes com fibromialgia. A Estimulação Transcraniana por Corrente Contínua (ETCC) é eficaz para o controle da dor.
Objetivo
O objetivo deste estudo foi avaliar os efeitos analgésicos e neuromoduladores de uma combinação de NBD e ETCC em pacientes com fibromialgia.
Métodos
Este foi um estudo randomizado, duplo-cego, paralelo, controlado por placebo/simulação (NCT04502251; RBR-7HK8N) no qual 86 mulheres com fibromialgia foram incluídas e o consentimento informado por escrito foi obtido delas. Os pacientes foram alocados em quatro grupos: NBD + ETCC (n = 21), NBD + ETCC Sham (n = 22), placebo + ETCC (n = 22) e placebo+ETCC Sham (n = 21). A intervenção NBD ou placebo (p.o.) durou 26 dias; nas últimas cinco sessões, foi aplicada ETCC (simulada ou ativa, 20 min, 2 mA). As seguintes categorias foram avaliadas: sociodemográficas, Escala Visual Analógica de Dor (VAS), Escala de Catastrofização da Dor (PCS), Inventário de Ansiedade Estado-Traço (IDATE), Questionário de Impacto da Fibromialgia (FIQ), Inventário de Depressão de Beck (BDI-II), Perfil de Escala de Dor Crônica (PCP:S), Limiar de Pressão da Dor (PPT) e Modulação da Dor Condicionada (CPM). Amostras de sangue foram coletadas para análise dos níveis séricos de BDNF.
Resultados
No início do estudo, nenhuma diferença significativa foi encontrada em relação a todas as medidas. A dor VAS foi significativamente reduzida nos grupos NBD + ETCC (p = 0,010), NBD + ETCC Simulado (p = 0,001) e placebo+ETCC Simulado (p = 0,009). No PCP:S, o grupo NBD+ETCC apresentou redução na frequência e intensidade da dor (p = 0,001), efeito da dor nas atividades (p = 0,014) e nas emoções (p = 0,008). Os sintomas depressivos diminuíram após todas as intervenções ativas (p > 0,001).
Conclusão
A combinação de NBD+ETCC tem possíveis benefícios na redução da frequência e intensidade da dor; no entanto, foi observado efeito placebo na dor com a EVA, devendo ser realizados mais estudos para analisar a possível associação.
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References
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