Repetitive Transcranial Magnetic Stimulation for Fibromyalgia: Systematic Review and Meta-Analysis.

BACKGROUND: Fibromyalgia (FM) is a prevalent chronic pain syndrome with few effective therapeutic options available. Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapeutic alternative for this condition; however, results have been mixed. OBJECTIVES: To evaluate the efficacy of rTMS on FM, a comprehensive systematic review and meta-analysis were performed. METHODS: Relevant published, English and Portuguese language, randomized clinical trials (RCT) comparing rTMS (irrespective of the stimulation protocol) to sham stimulation for treating FM pain intensity, depression, and/or quality of life (QoL) were identified, considering only those with low risk for bias. Trials available until April 2014 were searched through MEDLINE, EMBASE, the Cochrane Library Databases, and other 26 relevant medical databases covering from every continent. The outcomes for pain, depression, and QoL assessed closest to the 30th day after rTMS treatment were extracted, and changes from baseline were calculated to compare the effects of rTMS vs. placebo. RESULTS: One hundred and sixty-three articles were screened, and five with moderate to high quality were included. rTMS improved QoL with a moderate effect size (Pooled SMD = -0.472 95%CI = -0.80 to -0.14); it showed a trend toward reducing pain intensity (SMD = -0.64 95%CI = -0.31 to 0.017), but did not change depressive symptoms. CONCLUSION: In comparison with sham stimulation, rTMS demonstrated superior effect on the QoL of patients with FM 1 month after starting therapy. However, further studies are needed to determine optimal treatment protocols and to elucidate the mechanisms involved with this effect, which does not seem to be mediated by changes in depression, but that may involve pain modulation. Level of evidence 1b.

Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology.

BACKGROUND AND OBJECTIVES: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility. METHODS: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37). RESULTS: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%). CONCLUSION: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Neuroplastic Effects of Transcranial Direct Current Stimulation on Painful Symptoms Reduction in Chronic Hepatitis C: A Phase II Randomized, Double Blind, Sham Controlled Trial.

INTRODUCTION: Pegylated Interferon Alpha (Peg-IFN) in combination with other drugs is the standard treatment for chronic hepatitis C infection (HCV) and is related to severe painful symptoms. The aim of this study was access the efficacy of transcranial direct current stimulation (tDCS) in controlling the painful symptoms related to Peg-IFN side effects. MATERIALS AND METHODS: In this phase II double-blind trial, twenty eight (n = 28) HCV subjects were randomized to receive either 5 consecutive days of active tDCS (n = 14) or sham (n = 14) during 5 consecutive days with anodal stimulation over the primary motor cortex region using 2 mA for 20 min. The primary outcomes were visual analogue scale (VAS) pain and brain-derived neurotrophic factor (BDNF) serum levels. Secondary outcomes were the pressure-pain threshold (PPT), the Brazilian Profile of Chronic Pain: Screen (B-PCP:S), and drug analgesics use. RESULTS: tDCS reduced the VAS scores (P < 0.003), with a mean pain drop of 56% (p < 0.001). Furthermore, tDCS was able to enhance BDNF levels (p < 0.01). The mean increase was 37.48% in the active group. Finally, tDCS raised PPT (p < 0.001) and reduced the B-PCP:S scores and analgesic use (p < 0.05). CONCLUSIONS: Five sessions of tDCS were effective in reducing the painful symptoms in HCV patients undergoing Peg-IFN treatment. These findings support the efficacy of tDCS as a promising therapeutic tool to improve the tolerance of the side effects related to the use of Peg-IFN. Future larger studies (phase III and IV trials) are needed to confirm the clinical use of the therapeutic effects of tDCS in such condition. TRIAL REGISTRATION: Brazilian Human Health Regulator for Research with the approval number CAAE 07802012.0.0000.5327.