Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial

Abstract

The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.

Figure 1

Flowchart summarizing the study. Twenty participants were randomized into two groups receiving active-tDCS or sham-tDCS on M1. Only one participant of active-tDCS group withdrew during the stimulation phase. Missing data were treated by intention-to-treat analysis. None of the participants received medication throughout the trial. Patients tolerated the tDCS treatments well, and no adverse effects occurred.

Figure 2

(A) High-resolution computational model simulation of brain current flow during tDCS. The “M1-SO” assembly was simulated by sponge with anode positioned vertically over 10–20, location C3, and cathode positioned horizontally on the contralateral-supraorbital, approximately over 10–20, location Fp2. (B) Current flow patterns on a slice (A/m²). The model predicted electric field maps generated in outer cortical regions. Our results show diffuse and clustered brain current flow that includes left motor regions, as well as other regions implicated in treatment of pain and other regions of interest. (in V/m: M1 ipsilateral 0.23, contralateral 0.15, left DLPFC 0.23, nucleus accumbens 0.22, and cingulate 0.25). (C) Consecutive coronal slices and brain current flow.

Figure 3

(A) Mean visual analog scale (VAS) before treatment (baseline), on days 1 and 5 (during treatment) and follow-up. Error bars denote SEM. (B) Mean McGill score before treatment (baseline), on days 1 and 5 (during treatment) and follow-up. *p < 0.05. (C) Mean daily VAS pain recording. tDCS: describes the five days of treatment. After: denotes the follow-up period. A statistically significant decrease in pain was found only in Active-tDCS (p < 0.05, Friedman).