Abstract
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.
Highlights
A recent national survey estimates that 3–4% of Americans adults have been receiving long-term opioid therapy (Dowell et al, 2016), and it estimated that almost 2 million meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for dependence or abuse (Florence et al, 2016)
TDCS effects are likely to be transcranial direct current stimulation (tDCS), Pain and Opioids: A Review neuroplasticity state dependent, since previous study found that serum brain-derived neurotrophic factor (BDNF) predicts the impact of tDCS on behavioral measures in chronic pain conditions (Souza et al, 2018). This integrative review with meta-analysis has the following aims: (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 descending pain inhibitory system (DPIS). (ii) To show evidence about the tDCS as an approach to treat chronic pain. (iii) To discuss the effect of tDCS on DPMS and how its impact 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
We excluded articles if they met the following criteria: studies written in other languages than English, Portuguese, or Spanish; studies that do not reported pain as an outcome;
Summary
A recent national survey estimates that 3–4% of Americans adults have been receiving long-term opioid therapy (Dowell et al, 2016), and it estimated that almost 2 million meet the DSM-IV criteria for dependence or abuse (Florence et al, 2016). Even if research signs of progress and new targets appear for treating acute and chronic pain, opioids still. Opioid treatments induce several side effects, among them, are the analgesic tolerance and opioid-induced hyperalgesia (OIH). These phenomena are closely related to the dysfunction of the descending pain inhibitory system (DPIS). Thereby, we conduct the reader to a brainstorm of this question to integrate concepts related to pain, opioids effects as neuromodulators (analgesia, tolerance, and OIH and dysfunction of descending pain inhibitory system) and the impact of transcranial neuromodulatory techniques. Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS)
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