Transcranial Direct Current Stimulation Combined with Aerobic Exercise to Optimize Analgesic Responses in Fibromyalgia: A Randomized Placebo-Controlled Clinical Trial

Abstract

Fibromyalgia is a chronic pain syndrome that is associated with maladaptive plasticity in neural central circuits. One of the neural circuits that are involved in pain in fibromyalgia is the primary motor cortex. We tested a combination intervention that aimed to modulate the motor system: transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) and aerobic exercise (AE). In this phase II, sham-controlled randomized clinical trial, 45 subjects were assigned to 1 of 3 groups: tDCS + AE, AE only, and tDCS only. The following outcomes were assessed: intensity of pain, level of anxiety, quality of life, mood, pressure pain threshold, and cortical plasticity, as indexed by transcranial magnetic stimulation. There was a significant effect for the group-time interaction for intensity of pain, demonstrating that tDCS/AE was superior to AE [F (13, 364) = 2.25, p = 0.007] and tDCS [F (13, 364) = 2.33, p = 0.0056] alone. Post-hoc adjusted analysis showed a difference between tDCS/AE and tDCS group after the first week of stimulation and after 1 month intervention period (p = 0.02 and p = 0.03, respectively). Further, after treatment there was a significant difference between groups in anxiety and mood levels. The combination treatment effected the greatest response. The three groups had no differences regarding responses in motor cortex plasticity, as assessed by TMS. The combination of tDCS with aerobic exercise is superior compared with each individual intervention (cohen's d effect sizes > 0.55). The combination intervention had a significant effect on pain, anxiety and mood. Based on the similar effects on cortical plasticity outcomes, the combination intervention might have affected other neural circuits, such as those that control the affective-emotional aspects of pain.

Trial registration: (www.ClinicalTrials.gov), identifier NTC02358902.

Keywords: aerobic exercise; combined therapy; fibromyalgia; motor cortex; transcranial direct current stimulation (tDCS).

Figure 1

Research flowchart.

Figure 2

Methodology of intervention. Subjects received intervention with tDCS during the first week for five consecutive days, associated with aerobic exercise training performed three times a week for a month.

Figure 3

Illustration of interventions in combination, tDCS/AE group which was performed aerobic exercise in combination with tDCS.

Figure 4

Response of pain intensity (VNS pain). T1, assessment after the fifth day of intervention; T2, assessment after 1 month of intervention; T3, assessment after 1 month of the end of the intervention (follow-up 1); T4, assessment after 2 months of the end of the intervention (follow-up 2). Data presented as mean and standard error. ^*Statistical analysis demonstrated significant result for T1 (p = 0.02) and at T2 (p = 0.03) between tDCS/AE group and tDCS group.

Figure 5

Response for level of anxiety (VNS anxiety). T1, assessment after the fifth day of intervention; T2, assessment after 1 month of intervention; T3, assessment after 1 month of the end of the intervention (follow-up 1); T4, assessment after 2 months of the end of the intervention (follow-up 2). Paired evaluation between groups p < 0.001. Data presented as mean and standard error.

Figure 6

Data for pressure pain threshold. Group tDCS/AE demonstrating a relative of the pressure pain threshold increased, maintained during periods of follow-up. Group AE slight increase after the intervention, apparently not maintained at follow-up period. tDCS group with mild increase in the pressure pain threshold, being held in the follow-up period. No statistical significant data were observed. Data shown as mean and standard error.

Figure 7

Data for cortical excitability. (A) Data for motor evoked potential (MEP). There was an increased excitability in the tDCS/AE group until the end of the intervention, not being maintained after the period of follow-up. For tDCS group there was an increase in cortical excitability after just 1 week period of intervention that occurred with active stimulation. The EA group showed a slight decrease in MEP after the intervention. (B) Intracortical facilitation. There was a slight decrease in intracortical facilitation, represented by decreased amplitude of MEP's only in group tDCS/AE. (C) Intracortical inhibition. There was an increase in intracortical inhibition during the protocol period for tDCS/AE group, and in the follow-up periods an increase above the baseline. No statistically significant findings were observed. Data shown as mean and standard error.