CLINICAL TRIAL published: 19 November 2018 doi: 10.3389/fnhum.2018.00406 Edited by: Filippo Brighina, Università degli Studi di Palermo, Italy Reviewed by: Gianluca Coppola, Fondazione GB Bietti (IRCCS), Italy Yelena Granovsky, Rambam Health Care Campus, Israel *Correspondence: Wolnei Caumo wcaumo@hcpa.edu.br Received: 13 June 2018 Accepted: 20 September 2018 Published: 19 November 2018 Citation: Deitos A, Soldatelli MD, Dussán-Sarria JA, Souza A, da Silva Torres IL, Fregni F and Caumo W (2018) Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study. Front. Hum. Neurosci. 12:406. doi: 10.3389/fnhum.2018.00406 Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study Alícia Deitos 1 , Matheus Dorigatti Soldatelli 1,2 , Jairo Alberto Dussán-Sarria 1 , Andressa Souza 2,3 , Iraci Lucena da Silva Torres 4 , Felipe Fregni 5,6 and Wolnei Caumo 1,2,7,8 * 1 Post-Gradaution in Medical Science at Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 2 Laboratory of Pain and Neuromodulation, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 3 La Salle University Center, Canoas, Brazil, 4 Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 5 Department of Neurology, Harvard Medical School, Boston, MA, United States, 6 Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 7 Anesthesiologist, Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 8 Surgery Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Background: The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes. Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication. Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; −57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, −26 to 46.00) and the placebo increased it Frontiers in Human Neuroscience | www.frontiersin.org 1 November 2018 | Volume 12 | Article 406