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.

Neural signature of tDCS, tPCS and their combination: Comparing the effects on neural plasticity

“…Therefore, a single stimulation session might not be enough to generate important clinical changes. Finally, it is more and more evident that the effects of tDCS seem to be greater when coupled with a specific task [38–40]. …”

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

“…In nine studies using a structured questionnaire on the occurrence of AEs in migraine (Antal et al, 2011a; Dasilva et al, 2012; Poreisz et al, 2007; Wickmann et al, 2015), fibromyalgia (Fagerlund et al, 2015; Mendonca et al, 2016), temporomandibu-lar disorders (Donnell et al, 2015), irritable bowel syndrome (Volz et al, 2016), or a mixture of various neuropathic and non-neuropathic pain syndromes (Antal et al, 2010) the frequency of reported AEs was 20–50% higher than in studies with spontaneous reporting. Here also the most frequent AEs were tingling at the stimulation site (51% of either active or sham), and sleepiness or fatigue (39% after active and 45% after sham).…”

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

“…For example, transcranial magnetic stimulation (rTMS) involves using a magnetic field generator to stimulate small regions of the affected brain region. Thus far, rTMS has been shown to be an effective treatment for burning mouth syndrome [191], complex regional pain syndrome [192], fibromyalgia [193,194], neuropathic pain [195,196,197], depressive disorders [198] and to a lesser degree PTSD and other anxiety disorders [199,200]. It has been proposed to prevent or revert the ongoing maladaptive plasticity within the pain matrix [201], and modify opioidergic, glutamatergic, gamma-aminobutyric acidergic, and serotoninergic neurotransmissions [202].…”