Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique which has been widely studied for the treatment of chronic pain. It is considered a promising and safe alt...

One of the potential mechanisms of motor cortex stimulation by noninvasive brain stimulation (NIBS) effects on pain is through the restoration of the defective endogenous inhibitory pain pathways. However, there are still limited data on quantitative sensory testing (QST), including conditioned pain modulation (CPM), supporting this mechanism. This systematic review and meta-analysis aimed to evaluate the effects of noninvasive motor cortex stimulation on pain perception as indexed by changes in QST outcomes. Database searches were conducted until July 2019 to include randomized controlled trials that performed sham-controlled NIBS on the motor cortex in either the healthy and/or pain population and assessed the QST and CPM. Quality of studies was assessed through the Cochrane tool. We calculated the Hedge's effect sizes of QST and CPM outcomes and their 95% confidence intervals (95% CIs) and performed random-effects meta-analyses. Thirty-eight studies were included (1178 participants). We found significant increases of pain threshold in healthy subjects (ES = 0.16, 95% CI = 0.02-0.31, I² = 22.2%) and pain populations (ES = 0.48, 95% CI = 0.15-0.80, I² = 68.8%), and homogeneous higher CPM effect (pain ratings reduction) in healthy subjects (ES = −0.39, 95% CI = −0.64 to −0.14, I² = 17%) and pain populations (ES = −0.35, 95% CI = −0.60 to −0.11, I² = 0%) in the active NIBS group compared with sham. These results support the idea of top-down modulation of endogenous pain pathways by motor cortex stimulation as one of the main mechanisms of pain reduction assessed by QST, which could be a useful predictive and prognostic biomarker for chronic pain personalized treatment with NIBS.

Background: The use of non-invasive brain stimulation (NIBS) combined with exercise could produce synergistic effects on chronic pain conditions. This study aims to evaluate the efficacy and safety of NIBS combined with exercise to treat chronic pain as well as to describe the parameters used to date in this combination. Methods: The search was carried out in Medline, Central, Scopus, Embase, and Pedro until November 2019. Randomized clinical trials (RCTs) and quasi-experimental studies reporting the use of non-invasive brain stimulation and exercise on patients with chronic pain were selected and revised. Results: The authors included eight studies (RCTs), reporting eight comparisons (219 participants). Authors found a significant and homogeneous pain decrease (ES: -0.62, 95% CI:-0.89 to -0.34; I2= 0.0%) in favor of the combined intervention compared to sham NIBS + exercise, predominantly by excitatory (anodal tDCS/rTMS) motor cortex stimulation. Regarding NIBS techniques, the pooled effect sizes were significant for both tDCS (ES: -0.59, 95% CI: -0.89 to -0.29, I2= 0.0%) and rTMS (ES: -0.76, 95% CI: -1.41 to -0.11, I2=0.0%). Conclusions: This meta-analysis suggests a significant moderate to large effects of the NIBS and exercise combination in chronic pain. The authors discuss the potential theoretical framework for this synergistic effect.

Introduction Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control. Methods and analysis A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)—primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study—CPM and TSPS—and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables. Ethics and dissemination This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications. Trial registration number NCT03371225.

The COVID-19 outbreak has forced most of the global population to lock-down and has put in check the health services all over the world. Current predictive models are complex, region-dependent, and might not be generalized to other countries. However, a 150-year old epidemics law promulgated by William Farr might be useful as a simple arithmetical model (percent increase [R1] and acceleration [R2] of new cases and deaths) to provide a first sight of the epidemic behavior and to detect regions with high predicted dynamics. Thus, this study tested Farr’s Law assumptions by modeling COVID-19 data of new cases and deaths. COVID-19 data until April 10, 2020, was extracted from available countries, including income, urban index, and population characteristics. Farr’s law first (R₁) and second ratio (R₂) were calculated. We constructed epidemic curves and predictive models for the available countries and performed ecological correlation analysis between R₁ and R₂ with demographic data. We extracted data from 210 countries, and it was possible to estimate the ratios of 170 of them. Around 42·94% of the countries were in an initial acceleration phase, while 23·5% already crossed the peak. We predicted a reduction close to zero with wide confidence intervals for 56 countries until June 10 (high-income countries from Asia and Oceania, with strict political actions). There was a significant association between high R₁ of deaths and high urban index. Farr’s law seems to be a useful model to give an overview of COVID-19 pandemic dynamics. The countries with high dynamics are from Africa and Latin America. Thus, this is a call to urgently prioritize actions in those countries to intensify surveillance, to re-allocate resources, and to build healthcare capacities based on multi-nation collaboration to limit onward transmission and to reduce the future impact on these regions in an eventual second wave.