Efeitos da estimulação transcraniana de corrente contínua e sugestão hipnótica na tolerância à dor e excitabilidade cortical na fibromialgia : um ensaio clínico randomizado cruzado

Base teórica: Fibromialgia está associada a uma função deteriorada da inibição cortical. A estimulação transcraniana de corrente contínua anodal (a-ETCC) e a sugestão de analgesia hipnótica têm apresentado efeitos positivos na melhora dos escores de dor em pacientes com esta síndrome de dor crônica. Porém ainda existe uma lacuna na compreensão do impacto das técnicas no processamento cortical da dor e na excitabilidade cortical. Objetivos: Comparar os efeitos da sugestão de analgesia hipnótica, da a-ETCC sobre o córtex dorsolateral pré-frontal esquerdo (l-DLPFC) e de um teste de repouso nas medidas psicofísicas de dor [(Cold Pressor Test (CPT) (desfecho primário) e Limiar de Dor ao Calor (HPTh)]. Assim como seus efeitos nas medidas de excitabilidade cortical [potencial motor evocado (MEP) (desfecho primário), inibição intracortical curta (SICI), facilitação intracortical (ICF), e período silente cortical (CSP)]. Métodos: Este ensaio clínico randomizado cruzado cego incluiu 17 mulheres com fibromialgia, entre 18 e 65 anos de idade. Elas receberam aleatoriamente e de forma cruzada: a-ETCC sobre l-DLPFC, analgesia hipnótica, ou repouso. O ETCC foi aplicado com ânodo sobre o l-DLPFC e cátodo sobre o DLPFC direito, com estimulação em intensidade de 2mA. Ambas as intervenções foram aplicadas por 20 minutos. O efeito das intervenções foi avaliado pela mudança absoluta na porcentagem do pré- ao pós- intervenção. Resultados: Um modelo MANOVA seguido por um ajuste post hoc para comparações múltiplas por Teste de Bonferroni revelou que as sugestões hipnóticas mostraram uma mudança mais significativa no CPT do que a-tDCS e repouso. As médias (SD) na analgesia hipnótica comparada com a-ETCC foi 34.82 (40.89) vs. 6.14 (32.01), respectivamente. O tamanho de efeito (ES) foi moderado [Cohen's f=0.79]. As médias (SD) da analgesia hipnótica comparada com a o repouso foram 34.82 (40.89) vs. 1.41 (24.36)], respectivamente. O ES foi grande [Cohen's f=0.99]. a-ETCC mostrou um aumento significativo comparado com a analgesia hipnótica no MEP e SICI. As médias do MEP (SD) na a-ETCC e na sugestão hipnótica foram 42.84 (43.47) vs. -7.43 (40.94), respectivamente. O ES foi grande [Cohen's f=1]. As médias (SD) do SICI na a-ETCC e na sugestão hipnótica foram 63.22 (67.50) vs. 0.59 (50.06), respectivamente. O tamanho do efeito foi grande [Cohen's f=1.06]. Conclusão: Esse estudo confirmou efeitos distintos da hipnose e da a-ETCC sobre a tolerância à dor e seus efeitos na excitabilidade cortical na fibromialgia. Enquanto a hipnose afetou mecanismos contra-regulatórios envolvidos na tolerância à dor, a a-ETCC bifrontal com ânodo sobre o l-DLPFC aumentou a excitabilidade nas vias cortico-espinhais e a inibição intracortical.Background: Fibromyalgia has been linked with a deteriorated function of cortical inhibition. The anodal transcranial direct current stimulation (a-tDCS) and hypnotic analgesia suggestion have revealed beneficial effects to improve pain scores. However, persist a gap to comprehend their impact on cortical pain processing and cortico-spinal excitability. Objectives: To compare the effects of hypnotic analgesia suggestion, a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC) and rest-testing on psychophysical pain measures [(Cold Pressor Test (CPT) (primary outcome) and Heat Pain Threshold (HPTh)]. As well as in the cortical excitability measures [motor evoked potential (MEP) (primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP)]. Methods: This randomized, blind, crossover trial included 17 women with fibromyalgia, aged from 18 to 65 years old. They received a random and crossover order a-tDCS over the l-DLPFC, hypnotic analgesia, or a rest-testing. The tDCS was performed with anode over l–DLPFC and cathode over right DLPFC, with a current intensity of 2mA. All interventions lasted 20 minutes each. The effect of interventions was assessed by the absolute change variation in percentage (from pre- to post-intervention). Results: A MANOVA model followed by post hoc adjustment for multiple comparisons by Bonferroni's test revealed that the hypnotic suggestions showed a more significant change on CPT than a-tDCS and rest-testing. The mean (SD) of hypnotic's analgesia compared to a-tDCS was 34.82 (40.89) vs. 6.14 (32.01), respectively. The effect size (ES) was moderate [Cohen's f=0.79]. The mean (SD) of hypnotic analgesia compared to the rest testing was 34.82 (40.89) vs. 1.41 (24.36)], respectively. The ES was large [Cohen's f=0.99]. a-tDCS showed a significant increase compared to hypnotic's analgesia in the MEP and SICI. The MEP means (SD) in a-tDCS and the hypnotic suggestion was 42.84 (43.47) vs. -7.43 (40.94), respectively. The effect size was large [Cohen's f=1]. The means (SD) of SICI in the a-tDCS and the hypnotic suggestion was 63.22 (67.50) vs. 0.59 (50.06), respectively. The effect size was large [Cohen's f=1.06]. Conclusion: This study confirms differences in the hypnosis and tDCS effects over pain tolerance and its effects on the corticospinal excitability in fibromyalgia. While hypnosis affects contra-regulating mechanisms involved in pain tolerance, the bifrontal a-tDCS with anode on the left DLPFC up-regulates the excitability of corticospinal pathways and intracortical inhibition

The hypnotic analgesia suggestion mitigated the effect of the transcranial direct current stimulation on the descending pain modulatory system : a proof of concept study

Objective: We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF). Materials and Methods: Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA. Results: A generalized linear model revealed a significant main effect for the intervention group (P <0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was −0.25 (0.43). The (Δ) pain score on NPS (0–10) during CPM-test in the other three groups was a-tDCS=−0.54 (0.41), HS −0.01 (0.41) and stDCS/HS=−0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo. Conclusion: These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT

The hypnotic analgesia suggestion mitigated the effect of the transcranial direct current stimulation on the descending pain modulatory system : a proof of concept study

Objective: We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF). Materials and Methods: Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA. Results: A generalized linear model revealed a significant main effect for the intervention group (P <0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was −0.25 (0.43). The (Δ) pain score on NPS (0–10) during CPM-test in the other three groups was a-tDCS=−0.54 (0.41), HS −0.01 (0.41) and stDCS/HS=−0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo. Conclusion: These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT

Comparison of hypnotic suggestion and transcranial direct-current stimulation effects on pain perception and the descending pain modulating system : a crossover randomized clinical trial

Objectives: This paper aims to determine if hypnotic analgesia suggestion and transcranial direct-current stimulation (tDCS) have a differential effect on pain perception. We hypothesized that transcranial direct-current stimulation would be more effective than hypnotic analgesia suggestion at changing the descending pain modulating system, whereas the hypnotic suggestion would have a greater effect in quantitative sensory testing. Design: This is a randomized, double blind and crossover trial. Settings: All stages of this clinical trial were performed at the Laboratory of Pain and Neuromodulation of the Hospital de Clínicas de Porto Alegre. Subjects: Were included 24 healthy females aged from 18 to 45 years old, with a high susceptibility to hypnosis, according to the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C (15). Methods: The subjects received a random and crossover transcranial direct-current stimulation over the dorsolateral prefrontal cortex (2 mA for 20 min) and hypnotic analgesia (20 min). Results: Only hypnotic suggestion produced changes that are statistically significant from pre- to post-intervention in the following outcomes measures: heat pain threshold, heat pain tolerance, cold pressure test, and serum brain-derivate-neurotrophic-factor. The analysis showed a significant main effect for treatment (F = 4.32; P = 0.04) when we compared the delta-(1) of conditioned pain modulation task between the transcranial direct-current stimulation and hypnotic suggestion groups. Also, the change in the brain-derivate-neurotrophic-factor was positively correlated with the conditioned pain modulation task. Conclusion: The results confirm a differential effect between hypnotic suggestion and transcranial direct-current stimulation on the pain measures. They suggest that the impact of the interventions has differential neural mechanisms, since the hypnotic suggestion improved pain perception, whereas the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03744897. Perspective: These findings highlight the effect of hypnotic suggestion on contraregulating mechanisms involved in pain perception, while the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. They could help clinicians comprehend the mechanisms involved in hypnotic analgesia and transcranial direct-current stimulation and thus may contribute to pain and disability management