Background: Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS).Objectives: This integrative review with meta-analysis aimed: (i) To discuss the potential mechanisms involved in analgesic tolerance and opioid-induced hyperalgesia (OIH). (ii) To examine how the opioid can affect the function of DPIS. (ii) To show evidence about the tDCS as an approach to treat acute and chronic pain. (iii) To discuss the effect of tDCS on DPIS and how it can counter-regulate the OIH. (iv) To draw perspectives for the future about the tDCS effects as an approach to improve the dysfunction in the DPIS in chronic non-cancer pain.Methods: Relevant published randomized clinical trials (RCT) comparing active (irrespective of the stimulation protocol) to sham tDCS for treating chronic non-cancer pain were identified, and risk of bias was assessed. We searched trials in PubMed, EMBASE and Cochrane trials databases. tDCS protocols accepted were application in areas of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), or occipital area.Results: Fifty-nine studies were fully reviewed, and 24 with moderate to the high-quality methodology were included. tDCS improved chronic pain with a moderate effect size [pooled standardized mean difference; −0.66; 95% confidence interval (CI) −0.91 to −0.41]. On average, active protocols led to 27.26% less pain at the end of treatment compared to sham [95% CI; 15.89–32.90%]. Protocol varied in terms of anodal or cathodal stimulation, areas of stimulation (M1 and DLPFC the most common), number of sessions (from 5 to 20) and current intensity (from 1 to 2 mA). The time of application was 20 min in 92% of protocols.Conclusion: In comparison with sham stimulation, tDCS demonstrated a superior effect in reducing chronic pain conditions. They give perspectives that the top-down neuromodulator effects of tDCS are a promising approach to improve management in refractory chronic not-cancer related pain and to enhance dysfunctional neuronal circuitries involved in the DPIS and other pain dimensions and improve pain control with a therapeutic opioid-free. However, further studies are needed to determine individualized protocols according to a biopsychosocial perspective.

Background: Remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS) modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a)-t-DCS would be more effective than sham(s)-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT) assessed by the Numerical Pain Score (NPS 0-10) and we evaluated the function of the descending pain modulatory system (DPMS) by the change on the NPS (0–10) during the conditioned pain modulation (CPM)-task (primary outcomes). We tested whether a-tDCS would be more effective than s-tDCS to improve pain perception assessed by the heat pain threshold (HPT) and the reaction time during the ice-water pain test (IPT) (secondary outcomes).Methods: This double-blinded, factorial randomized trial included 48 healthy males, ages ranging 19–40 years. They were randomized into four equal groups: a-tDCS/saline, s-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. tDCS was applied over the primary motor cortex, during 20 min at 2 mA, which was introduced 10 min after starting remifentanil infusion at 0.06 μg⋅kg-1⋅min-1 or saline.Results: An ANCOVA mixed model revealed that during the rCOLDT, there was a significant main effect on the NPS scores (F = 3.81; P = 0.01). The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD) 5.49 (1.04)] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62)]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11 (1.2)] and [3.15 (1.62)], respectively. The effect of sedation induced by remifentanil during the rCOLDT was not significant (F = 0.76; P = 0.38). Remifentanil groups showed positive scores in the NPS (0–10) during the CPM-task, that is, it produced a disengagement of the DPMS. Also, s-tDCS/Remifentanil compared to a-tDCS showed lower HPT and larger reaction-time during the IPT.Conclusion: These findings suggest that effects of a-tDCS prevent the summation response induced by r-IH during rCOLDT and the a-tDCS blocked the disengagement of DPMS. Thereby, tDCS could be considered as a new approach to contra-regulate paradoxical mechanisms involved in the r-IH. Clinical trials identification: NCT02432677. URL:https://clinicaltrials.gov/.