Longer Cortical Silent Period Length Is Associated to Binge Eating Disorder: An Exploratory Study.

Introduction: Although binge eating disorder (BED) is an eating disorder and obesity is a clinical disease, it is known that both conditions present overlapped symptoms related to, at least partially, the disruption of homeostatic and hedonistic eating behavior pathways. Therefore, the understanding of neural substrates, such as the motor cortex excitability assessed by transcranial magnetic stimulation (TMS), might provide new insights into the pathophysiology of BED and obesity. Objectives: (i) To compare, among BED, obesity, ex-obese, and HC (healthy control) subjects, the cortical excitability indexed by TMS measures, such as CSP (cortical silent period; primary outcome), SICI (intracortical inhibition), and ICF (intracortical facilitation; secondary outcome). (ii) To explore the relationship of the CSP, eating behavior (e.g., restraint, disinhibition, and hunger), depressive symptoms, and sleep quality among the four groups (BED, obesity, ex-obese, and HC). Methods: Fifty-nine women [BED (n = 13), obese (n = 20), ex-obese (n = 12), and HC (n = 14)] comprise the total sample for this study. Assessments: cortical excitability measures (CSP, SICI, and ICF), inhibition response task by the Go/No-go paradigm, and instruments to assess the eating psychopathology (Three-Factor Eating Questionnaire, Eating Disorder Examination Questionnaire, and Binge Eating Scale) were used. Results: A MANCOVA analysis revealed that the mean of CSP was longer in the BED group compared with other three groups: 24.10% longer than the obesity group, 25.98% longer than the HC group, and 25.41% longer than the ex-obese group. Pearson's correlations evidenced that CSP was positively associated with both eating concern and binge eating scores. Conclusion: The findings point out that BED patients present longer CSP, which might suggest an upregulation of intracortical inhibition. Additionally, CSP was positively correlated with Binge Eating Scale and eating concern scores. Further studies are needed.

Large Treatment Effect With Extended Home-Based Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Fibromyalgia: A Proof of Concept Sham-Randomized Clinical Study.

This randomized, double-blind controlled trial tested the hypothesis that 60 sessions of home-based anodal (a)-transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC) would be better than home-based sham-tDCS to improve the widespread pain and the disability-related to pain. The anodal-tDCS (2 mA for 30 minutes) over the left DLPFC was self-administered with a specially developed device following in-person training. Twenty women, 18 to 65 years old were randomized into 2 groups [active-(a)-tDCS (n = 10) or sham-(s)-tDCS (n = 10)]. Post hoc analysis revealed that after the first 20 sessions of a-tDCS, the cumulative pain scores reduced by 45.65% [7.25 (1.43) vs 3.94 (1.14), active vs sham tDCS, respectively]. After 60 sessions, during the 12-week assessment, pain scores reduced by 62.06% in the actively group [visual analogue scale reduction, 7.25 (1.43) to 2.75 (.85)] compared to 24.92% in the s-tDCS group, [mean (SD) 7.10 (1.81) vs 5.33 (.90)], respectively. It reduced the risk for analgesic use in 55%. Higher serum levels of the brain-derived neurotrophic factor predicted higher decreases on the pain scores across of treatment. PERSPECTIVE: These findings bring 3 important insights: 1) show that an extended period of treatment (60 sessions, to date the largest number of tDCS sessions tested) for fibromyalgia induces large pain decreases (a large effect size of 1.59) and 2) support the feasibility of home-based tDCS as a method of intervention; 3) provide additional data on DLPFC target for the treatment of fibromyalgia. Finally, our findings also highlight that brain-derived neurotrophic factor to index neuroplasticity may be a valuable predictor of the tDCS effect on pain scores decreases across the treatment.

The Evaluation of Medication Adherence in Patients Infected With HCV Receiving Protease Inhibitors: A Pilot Study.

Adherence to treatment is essential for hepatitis C cure. Studies show the complexity of the treatment due to side effects, many pills, and rigor in the schedules. The aim of this study was to evaluate the adherence to treatment with protease inhibitor in patients with hepatitis C. It is a longitudinal, observational, prospective pilot study with patients with hepatitis C genotype 1. Bimonthly consultations and biweekly calls for 20 weeks were performed. Evaluation methods for adherence were Measure of Adherence to Treatment score, patient report, count pills, and sustained virological response. Twenty-two patients were enrolled. Mean age was 54.0 ± 8.72 years; 50% were men, educational level was 7.9 ± 3.89 years for the study, and intake of pills was 2.2 ± 1.60 per day. Adverse events reported were fatigue (90.9%), muscular pain (72.7%), and nausea (68.2%). In total, 71.4% of patients took 100% of medications and were classified as having a high degree of adherence to treatment. The sustained virological response was not significant in relation to the high or low adherence degree. Measure of Adherence to Treatment score is a good instrument to measure adherence to protease inhibitor treatment. The adherence of patients undergoing long-term and complex treatments improves when the multidisciplinary team follows up every 7-15 days. The patient's access to the team through additional phone calls or medical/nursing appointment is essential to improve adherence.

Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study.

Background: Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption of neuroplastic processes that mediate the equilibrium in the inhibitory systems stands out as a possible mechanism. Thus, the purpose of this cross-sectional exploratory study was: (i) to compare the motor cortex inhibition indexed by transcranial magnetic stimulation (TMS) measures [short intracortical inhibition (SICI) and intracortical facilitation (ICF)], as well as the function of descending pain modulatory systems (DPMS) among FM, MDD, and healthy subjects (HS); (ii) to compare SICI, ICF, and the role of DPMS evaluated by the change on Numerical Pain Scale (NPS) during the conditioned pain modulation test (CPM-test) between FM and MDD considering the BDNF-adjusted index; (iii) to assess the relationship between the role of DPMS and the BDNF-adjusted index, despite clinical diagnosis. Patients and Methods: A cohort of 63 women, aged 18 to 75 years [FM (n = 18), MDD (n = 19), and HC (n = 29)]. Results: The MANCOVA analysis revealed that the mean of SICI was 53.40% larger in FM compared to MDD [1.03 (0.50) vs. 0.55 (0.43)] and 66.99% larger compared to HC [1.03 (0.50) vs. 0.34 (0.19)], respectively. The inhibitory potency of the DPMS assessed by the change on the NPS during CPM-test was 112.29 % lower in the FM compared to MDD [0.22 (1.37) vs. -0.87 (1.49)]. The mean of BDNF from FM compared to MDD was 35.70% higher [49.82 (16.31) vs. 14.12 (8.86)]. In FM, the Spearman's coefficient between the change in the NPS during CPM-test with the SICI was Rho = -0.49, [confidence interval (CI) 95%; -0.78 to -0.03]. The BDNF-adjusted index was positively correlated with the disinhibition of the DPMS. Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM.

Intramuscular electrical stimulus potentiates motor cortex modulation effects on pain and descending inhibitory systems in knee osteoarthritis: a randomized, factorial, sham-controlled study.

BACKGROUND: Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS). OBJECTIVES: We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes. REGISTRATION: The trial is registered in Clinicaltrials.gov: NCT01747070. METHODS: Sixty women with KOA, aged 50-75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1-S2. RESULTS: A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P<0.0001). There existed a significant effect of time and a significant interaction between group and time (P<0.01 for both). The delta-(Δ) pain score on VAS in the a-tDCS/a-EIMS group was -3.59, 95% CI: -4.10 to -2.63. The (Δ) pain scores on VAS in the other three groups were: a-tDCS/s-EIMS=-2.13, 95% CI: -2.48 to -1.64; s-tDCS/a-EIMS=-2.25, 95% CI: -2.59 to -1.68; s-tDCS/s-EIMS MR =-1.77, 95% CI: -2.08 to -1.38. The a-tDCS/a-EIMS led to better effect in DPMS, PPT, analgesic use, and disability related to pain. CONCLUSION: This study provides additional evidence regarding additive clinical effects to improve pain measures and descending pain inhibitory controls when the neuromodulation of the primary motor cortex with tDCS is combined with a bottom-up modulation with EIMS in KOA. Also, it improved the ability to walk due to reduced pain and reduced analgesic use.

Potency of descending pain modulatory system is linked with peripheral sensory dysfunction in fibromyalgia: An exploratory study.

Fibromyalgia (FM) is characterized by chronic widespread pain whose pathophysiological mechanism is related to central and peripheral nervous system dysfunction. Neuropathy of small nerve fibers has been implicated due to related pain descriptors, psychophysical pain, and neurophysiological testing, as well as skin biopsy studies. Nevertheless, this alteration alone has not been previously associated to the dysfunction in the descending pain modulatory system (DPMS) that is observed in FM. We hypothesize that they associated, thus, we conducted a cross-sectional exploratory study.To explore small fiber dysfunction using quantitative sensory testing (QST) is associated with the DPMS and other surrogates of nociceptive pathways alterations in FM.We run a cross-sectional study and recruited 41 women with FM, and 28 healthy female volunteers. We used the QST to measure the thermal heat threshold (HTT), heat pain threshold (HPT), heat pain tolerance (HPT), heat pain tolerance (HPTo), and conditional pain modulation task (CPM-task). Algometry was used to determine the pain pressure threshold (PPT). Scales to assess catastrophizing, anxiety, depression, and sleep disturbances were also applied. Serum brain-derived neurotrophic factor (BDNF) was measured as a marker of neuroplasticity. We run multivariate linear regression models by group to study their relationships.Samples differed in their psychophysical profile, where FM presented lower sensitivity and pain thresholds. In FM but not in the healthy subjects, regression models revealed that serum BDNF was related to HTT and CPM-Task (Hotelling Trace = 1.80, P < .001, power = 0.94, R = 0.64). HTT was directly related to CPM-Task (B = 0.98, P = .004, partial-η = 0.25), and to HPT (B = 1.61, P = .008, partial η = 0.21), but not to PPT. Meanwhile, BDNF relationship to CPM-Task was inverse (B = -0.04, P = .043, partial-η = 0.12), and to HPT was direct (B = -0.08, P = .03, partial-η = 0.14).These findings high spot that in FM the disinhibition of the DPMS is positively correlated with the dysfunction in peripheral sensory neurons assessed by QST and conversely with serum BDNF.

Insights About the Neuroplasticity State on the Effect of Intramuscular Electrical Stimulation in Pain and Disability Associated With Chronic Myofascial Pain Syndrome (MPS): A Double-Blind, Randomized, Sham-Controlled Trial.

Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS). Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters. Methods: We included 24 right-handed female with chronic MPS, 19-65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12). Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19 (95%CI, -57.23 to -29.39) at 3 months of follow up. The relative risk for using analgesics was 2.95 (95% CI, 1.36 to 6.30) in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment [(Beta = -0.61, (-0.58 to -0.26)] and a more significant change from pre- to post-treatment on serum BDNF) (Beta = 0.67; CI95% = 0.07 to 1.26) were predictors to EIMS effect on pain and disability due to pain. Conclusion: These findings suggest that a bottom-up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it's long-term clinical impact on pain and disability due MPS. The trial is recorded in ClinicalTrials.gov: NCT02381171.

Home-Based Transcranial Direct Current Stimulation Device Development: An Updated Protocol Used at Home in Healthy Subjects and Fibromyalgia Patients.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) method, which modulates the membrane potential of neurons in the cerebral cortex by a low-intensity direct current. tDCS is a low-cost technique with minimal adverse effects and easy application. This neurostimulation method has a promising future to improve pain therapy, treatment of neuropsychiatric disorders, and physical rehabilitation. Current studies demonstrate the benefits of using tDCS over consecutive multiple sessions. However, the daily displacement to the specialized centers, travel costs, and disruptions to daily activities are some of the difficulties faced by patients. Thus, to be more comfortable, easy-to-use, and not disrupt daily commitments, a home-based tDCS was designed. Therefore, the objective of this study was to evaluate the feasibility of a portable tDCS device for home use in healthy subjects and fibromyalgia patients. Despite increased tDCS use and a reasonably large body of research on the effects across a range of clinical conditions, there is a limited amount of research on developing secure devices that guarantee the dose and contain a block system to avoid excessive use. Therefore, we used a tDCS device with a security system to permit daily use for 20 minutes with a minimal interval of 12 hours between sessions. A programmer preconfigures the equipment, which has a neoprene cap that allows the electrode positions in any assembly, according to individualized protocols for treatments or research. After, researchers can assess the effectiveness of treatment, and its adherence using information kept in the device software. Results suggest that the device is feasible for home use, with proper monitoring of adherence and contact impedance. There were reports of a few adverse effects, which do not differ from those reported in the literature in studies with the treatment under direct supervision.

Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential.

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

A Framework for Understanding the Relationship between Descending Pain Modulation, Motor Corticospinal, and Neuroplasticity Regulation Systems in Chronic Myofascial Pain.

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain. However, its neurobiological mechanisms are not entirely elucidated. Given the complex interaction between the networks involved in pain process, our approach, to providing insights into the neural mechanisms of pain, was to investigate the relationship between neurophysiological, neurochemical and clinical outcomes such as corticospinal excitability. Recent evidence has demonstrated that three neural systems are affected in chronic pain: (i) motor corticospinal system; (ii) internal descending pain modulation system; and (iii) the system regulating neuroplasticity. In this cross-sectional study, we aimed to examine the relationship between these three central systems in patients with chronic MPS of whom do/do not respond to the Conditioned Pain Modulation Task (CPM-task). The CPM-task was to immerse her non-dominant hand in cold water (0-1°C) to produce a heterotopic nociceptive stimulus. Corticospinal excitability was the primary outcome; specifically, the motor evoked potential (MEP) and intracortical facilitation (ICF) as assessed by transcranial magnetic stimulation (TMS). Secondary outcomes were the cortical excitability parameters [current silent period (CSP) and short intracortical inhibition (SICI)], serum brain-derived neurotrophic factor (BDNF), heat pain threshold (HPT), and the disability related to pain (DRP). We included 33 women, (18-65 years old). The MANCOVA model using Bonferroni's Multiple Comparison Test revealed that non-responders (n = 10) compared to responders (n = 23) presented increased intracortical facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater motor-evoked potential amplitude (µV) 1.93 (0.54) vs. 1.40 (0.27), as well a higher serum BDNF (pg/Ml) 32.56 (9.95) vs. 25.59 (10.24), (P < 0.05 for all). Also, non-responders presented a higher level of DRP and decreased HPT (P < 0.05 for all). These findings suggest that the loss of net descending pain inhibition was associated with an increase in ICF, serum BDNF levels, and DRP. We propose a framework to explain the relationship and potential directionality of these factors. In this framework we hypothesize that increased central sensitization leads to a loss of descending pain inhibition that triggers compensatory mechanisms as shown by increased motor cortical excitability.

Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition: An Exploratory Study.

Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0-10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use.In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0-10) during CPM-task.A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0-10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index.These findings support the hypothesis that the change in cortical plasticity in KOACP is associated with less intracortical inhibition, as measured by the CSP. These results show that the neural change in the motor cortex in KOACP is associated with pain and disability levels, and also with decreased activation of the endogenous pain-modulating system by a CPM-task.

Electrical Intramuscular Stimulation in Osteoarthritis Enhances the Inhibitory Systems in Pain Processing at Cortical and Cortical Spinal System.

OBJECTIVE: To determine if in knee osteoarthritis (KOA), one session of active electrical intramuscular stimulation (a-EIMS) compared with sham causes an effect on the motor cortex excitability parameters [motor evoked potential (MEP; the primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP)] and pain measurements [pain pressure threshold (PPT); visual analog scale (VAS) and change in numerical pain scale (NPS0-10 ) during the conditioned pain modulation (CPM)-task]. This study also set out to determine if serum brain-derived neurotrophic factor (BDNF) mediates the effect of treatment on the cortical spinal system as assessed by MEP and PPT. DESIGN: Randomized clinical trial. SUBJECTS AND METHODS: Women with KOA, 50-75-years old received a 30-min session of either sham (n = 13) or a-EIMS (n = 13) with 2 Hz. The pain measures and excitability parameters were measured before and immediately after a-EIMS or sham. RESULTS: The a-EIMS group compared with sham decreased the MEP by 31,67% [confidence interval (CI) 95%, 2.34-60.98]. For the secondary outcomes, the a-EIMS reduced the ICF and increased the CSP but not changed the SICI. The a-EIMS improved the pain reported on VAS, the PPT, and the score of the NPS (0-10) during the CPM-task The BDNF was negatively correlated with the PPT (r = -0.56). CONCLUSIONS: The serum BDNF revealed an inverse relationship with PPT independent of the treatment group. These results suggest that a-EIMS enhanced the corticospinal inhibitory systems in cortical and infracortical pain processing sites most likely by bottom-up regulation mechanisms.

Effect of Deep Intramuscular Stimulation and Transcranial Magnetic Stimulation on Neurophysiological Biomarkers in Chronic Myofascial Pain Syndrome.

OBJECTIVE: The aim was to assess the neuromodulation techniques effects (repetitive transcranial magnetic stimulation [rTMS] and deep intramuscular stimulation therapy [DIMST]) on pain intensity, peripheral, and neurophysiological biomarkers chronic myofascial pain syndrome (MPS) patients. DESIGN: Randomized, double blind, factorial design, and controlled placebo-sham clinical trial. SETTING: Clinical trial in the Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre (NCT02381171). SUBJECTS: We recruited women aged between 19- and 75-year old, with MPS diagnosis. METHODS: Patients were randomized into four groups: rTMS + DIMST, rTMS + sham-DIMST, sham-rTMS + DIMST, sham-rTMS + sham-DIMST; and received 10 sessions for 20 minutes each one (rTMS and DIMST). Pain was assessed by visual analogue scale (VAS); neurophysiological parameters were assessed by transcranial magnetic stimulation; biochemical parameters were: BDNF, S100ß, lactate dehydrogenase, inflammatory (TNF-α, IL6, and IL10), and oxidative stress parameters. RESULTS: We observed the pain relief assessed by VAS immediately assessed before and after the intervention (P < 0.05, F(1,3)= 3.494 and F(1,3)= 4.656, respectively); in the sham-rTMS + DIMST group and both three active groups in relation to sham-rTMS + sham-DIMST group, respectively. There was an increase in the MEP after rTMS + sham-DIMST (P < 0.05). However, there was no change in all-peripheral parameters analyzed across the treatment (P > 0.05). CONCLUSION: Our findings add additional evidence about rTMS and DIMST in relieving pain in MPS patients without synergistic effect. No peripheral biomarkers reflected the analgesic effect of both techniques; including those related to cellular damage. Additionally, one neurophysiological parameter (increased MEP amplitude) needs to be investigated.

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.

Repetitive transcranial magnetic stimulation increases the corticospinal inhibition and the brain-derived neurotrophic factor in chronic myofascial pain syndrome: an explanatory double-blinded, randomized, sham-controlled trial.

UNLABELLED: Chronic myofascial pain syndrome has been related to defective descending inhibitory systems. Twenty-four females aged 19 to 65 years with chronic myofascial pain syndrome were randomized to receive 10 sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). We tested if pain (quantitative sensory testing), descending inhibitory systems (conditioned pain modulation [quantitative sensory testing + conditioned pain modulation]), cortical excitability (TMS parameters), and the brain-derived neurotrophic factor (BDNF) would be modified. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analog scale on pain (analysis of variance, P < .01). Post hoc analysis showed that compared with placebo-sham, the treatment reduced daily pain scores by -30.21% (95% confidence interval = -39.23 to -21.20) and analgesic use by -44.56 (-57.46 to -31.67). Compared to sham, rTMS enhanced the corticospinal inhibitory system (41.74% reduction in quantitative sensory testing + conditioned pain modulation, P < .05), reduced the intracortical facilitation in 23.94% (P = .03), increased the motor evoked potential in 52.02% (P = .02), and presented 12.38 ng/mL higher serum BDNF (95% confidence interval = 2.32-22.38). No adverse events were observed. rTMS analgesic effects in chronic myofascial pain syndrome were mediated by top-down regulation mechanisms, enhancing the corticospinal inhibitory system possibly via BDNF secretion modulation. PERSPECTIVE: High-frequency rTMS analgesic effects were mediated by top-down regulation mechanisms enhancing the corticospinal inhibitory, and this effect involved an increase in BDNF secretion.

Association of anxiety with intracortical inhibition and descending pain modulation in chronic myofascial pain syndrome.

BACKGROUND: This study aimed to answer three questions related to chronic myofascial pain syndrome (MPS): 1) Is the motor cortex excitability, as assessed by transcranial magnetic stimulation parameters (TMS), related to state-trait anxiety? 2) Does anxiety modulate corticospinal excitability changes after evoked pain by Quantitative Sensory Testing (QST)? 3) Does the state-trait anxiety predict the response to pain evoked by QST if simultaneously receiving a heterotopic stimulus [Conditional Pain Modulation (CPM)]? We included females with chronic MPS (n = 47) and healthy controls (n = 11), aged 19 to 65 years. Motor cortex excitability was assessed by TMS, and anxiety was assessed based on the State-Trait Anxiety Inventory. The disability related to pain (DRP) was assessed by the Profile of Chronic Pain scale for the Brazilian population (B:PCP:S), and the psychophysical pain measurements were measured by the QST and CPM. RESULTS: In patients, trait-anxiety was positively correlated to intracortical facilitation (ICF) at baseline and after QST evoked pain (ß = 0.05 and ß = 0.04, respectively) and negatively correlated to the cortical silent period (CSP) (ß = -1.17 and ß = -1.23, respectively) (P <0.05 for all comparisons). After QST evoked pain, the DRP was positively correlated to ICF (ß = 0.02) (P < 0.05). Pain scores during CPM were positively correlated with trait-anxiety when it was concurrently with high DRP (ß = 0.39; P = 0.02). Controls' cortical excitability remained unchanged after QST. CONCLUSIONS: These findings suggest that, in chronic MPS, the imbalance between excitatory and inhibitory descending systems of the corticospinal tract is associated with higher trait-anxiety concurrent with higher DRP.

The relationship between cortical excitability and pain catastrophizing in myofascial pain.

UNLABELLED: Pain catastrophizing regularly occurs in chronic pain patients. It has been suggested that pain catastrophizing is a stable, person-based construct. These findings highlight the importance of investigating catastrophizing in conceptualizing specific approaches for pain management. One important area of investigation is the mechanism underlying pain catastrophizing. Therefore, this study explored the relationship between a neurophysiological marker of cortical excitability, as assessed by transcranial magnetic stimulation, and catastrophizing, as assessed by the Brazilian Portuguese Pain Catastrophizing Scale, in patients with chronic myofascial pain syndrome. The Pain Catastrophizing Scale is a robust questionnaire used to examine rumination, magnification and helplessness that are associated with the experience of pain. We include 24 women with myofascial pain syndrome. The Brazilian Portuguese Pain Catastrophizing Scale and cortical excitability were assessed. Functional and behavioral aspects of pain were evaluated with a version of the Profile of Chronic Pain scale and by multiple pain measurements (eg, pain intensity, pressure pain threshold, and other quantitative sensory measurements). Intracortical facilitation was found to be significantly associated with pain catastrophizing (ß = .63, P = .001). Our results did not suggest that these findings were influenced by other factors, such as age or medication use. Furthermore, short intracortical inhibition showed a significant association with pressure pain threshold (ß = .44, P = .04). This study elaborates on previous findings indicating a relationship between cortical excitability and catastrophizing. The present findings suggest that glutamatergic activity may be associated with mechanisms underlying pain catastrophizing; thus, the results highlight the need to further investigate the neurophysiological mechanisms associated with pain and catastrophizing. PERSPECTIVE: This study highlights the relationship between cortical excitability and catastrophizing. Cortical measures may illuminate how catastrophizing responses may be related to neurophysiological mechanisms associated with chronic pain.