Evidence of Anti-Inflammatory Effect of Transcranial Direct Current Stimulation in a CFA-Induced Chronic Inflammatory Pain Model in Wistar Rats.

INTRODUCTION: Given that chronic inflammatory pain is highly prevalent worldwide, it is important to study new techniques to treat or relieve this type of pain. The present study evaluated the effect of transcranial direct current stimulation (tDCS) in rats submitted to a chronic inflammatory model by nociceptive response, biomarker levels (brain-derived neurotrophic factor [BDNF] and interleukin [IL]-6 and IL-10), and by histological parameters. METHODS: Sixty-day-old male Wistar rats were used in this study and randomized by weight into 6 major groups: total control, control + sham-tDCS, control + active tDCS, total CFA, CFA + sham-tDCS, and CFA + active tDCS. After inflammatory pain was established, the animals were submitted to the treatment protocol for 8 consecutive days, according to the experimental group. The nociceptive tests (von Frey and hot plate) were assessed, and euthanasia by decapitation occurred at day 8 after the end of tDCS treatment, and the blood serum and central nervous structures were collected for BDNF and IL measurements. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (UFPel #4538). RESULTS: The tDCS treatment showed a complete reversal of the mechanical allodynia induced by the pain model 24 h and 8 days after the last tDCS session, and there was partial reversal of the thermal hyperalgesia at all time points. Serum BDNF levels were decreased in CFA + sham-tDCS and CFA + tDCS groups compared to the control + tDCS group. The control group submitted to tDCS exhibited an increase in serum IL-6 levels in relation to the other groups. In addition, there was a significant decrease in IL-10 striatum levels in control + tDCS, CFA, and CFA + sham-tDCS groups in relation to the control group, with a partial tDCS effect on the CFA pain model. Local histology demonstrated tDCS effects in decreasing lymphocytic infiltration and neovascularization and tissue regeneration in animals exposed to CFA. CONCLUSION: tDCS was able to reverse the mechanical allodynia and decrease thermal hyperalgesia and local inflammation in a chronic inflammatory pain model, with a modest effect on striatum IL-10 levels. As such, we suggest that analgesic tDCS mechanisms may be related to tissue repair by modulating the local inflammatory process.

The Application of Static Magnetic Stimulation Reduces Survival of SH-SY5Y Neuroblastoma Cells.

BACKGROUND/AIM: Central nervous system cancer is still a major public health issue. The effectiveness of treatments is limited and varies depending on the severity of disease. Therefore, there is a demand for the development of novel therapies. Static magnetic stimulation (SMS) emerges as a new therapeutic option. The aim of this study was to evaluate the SMS effects on neuroblastoma cells in culture. MATERIALS AND METHODS: SH-SY5Y neuroblastoma cells were exposed to 0.3T SMS for 6, 12, 24, 36, 72 h, and 6 days. Cell viability (MTT), cell death (annexin-V/PI staining) and cell cycle (DNA content), cell proliferation (CFSE), autophagy (acridine orange), and total mitochondrial mass (MitoTracker™ Red) were analyzed to establish the cellular response to SMS. RESULTS: The viability of SH-SY5Y cells was reduced after exposure to SMS for 24 h and 6 days (p<0.05), without differences for the other times (p>0.05); however, this effect was not related to cell death or cell cycle arrest (p>0.05). In contrast, the viability of human malignant melanoma (HMV-II) cells, used as a tumoral control, was not affected. In addition, stimulated SH-SY5Y cells presented a decrease in mitochondrial mass at both exposure times and a reduction in autophagy and cell proliferation after 6 days (p<0.05). CONCLUSION: SMS application appears to be a promising adjuvant therapy for the treatment of neuroblastoma since it decreases the survival of SH-SY5Y neuroblastoma cells.

tDCS and exercise improve anxiety-like behavior and locomotion in chronic pain rats via modulation of neurotrophins and inflammatory mediators.

Anxiety disorders cause distress and are commonly found to be comorbid with chronic pain. Both are difficult-to-treat conditions for which alternative treatment options are being pursued. This study aimed to evaluate the effects of transcranial direct current stimulation (tDCS), treadmill exercise, or both, on anxiety-like behavior and associated growth factors and inflammatory markers in the hippocampus and sciatic nerve of rats with neuropathic pain. Male Wistar rats (n = 216) were subjected to sham-surgery or sciatic nerve constriction for pain induction. Fourteen days following neuropathic pain establishment, either bimodal tDCS, treadmill exercise, or a combination of both was used for 20 min a day for 8 consecutive days. The elevated plus-maze test was used to assess anxiety-like behavior and locomotor activity during the early (24 h) or late (7 days) phase after the end of treatment. BDNF, TNF-ɑ, and IL-10 levels in the hippocampus, and BDNF, NGF, and IL-10 levels in the sciatic nerve were assessed 48 h or 7 days after the end of treatment. Rats from the pain groups developed an anxiety-like state. Both tDCS and treadmill exercise provided ethological and neurochemical alterations induced by pain in the early and/or late phase, and a modest synergic effect between tDCS and exercise was observed. These results indicate that non-invasive neuromodulatory approaches can attenuate both anxiety-like status and locomotor activity and alter the biochemical profile in the hippocampus and sciatic nerve of rats with neuropathic pain and that combined interventions may be considered as a treatment option.

Development and reliability of a new system for bedside evaluation of non-volitional knee extension force.

PURPOSE: Neuromuscular electrical stimulation (NMES) is a widely-used technique for diagnostic and therapeutic purposes. Here we developed and tested the reliability of a new NMES-dynamometer system for bedside evaluation of knee extensor muscle function. MATERIALS AND METHODS: Thirty-two healthy participants (16 men, 16 women; 27±5 years) completed two testing sessions, 7 days apart. On day 1, a single experienced rater, who repeated the evaluation on day 2 with two other raters, completed a standardized testing procedure. Participants were placed supine, with knees flexed and legs connected to the dynamometer. Maximal voluntary knee extensor isometric force (MVF) and supramaximal twitch force (TwF) were obtained. RESULTS: High intra-rater intraclass correlation coefficients were observed for both MVF (0.91) and TwF (0.94). MVF and TwF standard error of measurements (8.2%, 5.9%) and minimal detectable changes (16%, 11.6%) were low compared to mean values. High intraclass correlation coefficients were also observed for inter-rater comparisons of MVF (0.89) and TwF (0.86). Standard errors of measurements (MVF: 8.7%, TwF: 5.5%) and minimal detectable changes (MVF: 17.2%, TwF: 10.8%) were similar to intra-rater comparisons. CONCLUSION: The good reliability of the novel NMES-dynamometer system suggests it as an appropriate tool for the bedside evaluation of knee extensor muscle function.

Home-Based Transcranial Direct Current Stimulation for the Treatment of Symptoms of Depression and Anxiety in Temporal Lobe Epilepsy: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal - initial = -12.54 vs. -12.20, p = 0.68). The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842].

rTMS induces analgesia and modulates neuroinflammation and neuroplasticity in neuropathic pain model rats.

Neuropathic pain (NP) is related to the presence of hyperalgesia, allodynia, and spontaneous pain, affecting 7%-10% of the general population. Repetitive transcranial magnetic stimulation (rTMS) is applied for NP relief, especially in patients with refractory pain. As NP response to existing treatments is often insufficient, we aimed to evaluate rTMS treatment on the nociceptive response of rats submitted to an NP model and its effect on pro-and anti-neuroinflammatory cytokine and neurotrophin levels. A total of 106 adult male Wistar rats (60 days old) were divided into nine experimental groups: control, control + sham rTMS, control + rTMS, sham NP, sham neuropathic pain + sham rTMS, sham neuropathic pain + rTMS, NP, neuropathic pain + sham rTMS, and neuropathic pain + rTMS. NP establishment was achieved 14 days after the surgery to establish chronic constriction injury (CCI) of the sciatic nerve. Rats were treated with 5 min daily sessions of rTMS for eight consecutive days. Nociceptive behavior was assessed using von Frey and hot plate tests at baseline, after NP establishment, and post-treatment. Biochemical assays to assess the levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-10, were performed in the prefrontal cortex (PFC) and spinal cord tissue homogenates. rTMS treatment promoted a partial reversal of mechanical allodynia and total reversal of thermal hyperalgesia induced by CCI. Moreover, rTMS increased the levels of BDNF, TNF-α, and IL-10 in the PFC. rTMS may be a promising tool for the treatment of NP. The alterations induced by rTMS on neurochemical parameters may have contributed to the analgesic effect presented.

Repetitive Transcranial Magnetic Stimulation (rTMS) Reverses the Long-term Memory Impairment and the Decrease of Hippocampal Interleukin-10 Levels, both Induced by Neuropathic Pain in Rats.

Neuropathic pain (NP) is characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Repetitive transcranial magnetic stimulation (rTMS) is one of neuromodulatory techniques that induces satisfactory NP relief, including that from refractory pain patients. The objective of this study was to evaluate rTMS treatment over long term memory (LTM) and hippocampal BDNF and IL-10 levels in rats submitted to a NP model. A total of 81 adult (60-days old) male Wistar rats were randomly allocated to one of the following 9 experimental groups: control, control + sham rTMS, control + rTMS, sham neuropathic pain, sham neuropathic pain + sham rTMS, sham neuropathic pain + rTMS, neuropathic pain (NP), neuropathic pain + sham rTMS and neuropathic pain + rTMS. Fourteen days after the surgery for chronic constriction injury (CCI) of the sciatic nerve, NP establishment was accomplished. Then, rats were treated with daily 5-minute sessions of rTMS for eight consecutive days. LTM was assessed by the object recognition test (ORT) twenty-four hours after the end of rTMS treatment. Biochemical assays (BDNF and IL-10 levels) were performed in hippocampus tissue homogenates. rTMS treatment reversed the reduction of the discrimination index in the ORT and the hippocampal IL-10 levels in NP rats. This result shows that rTMS reverses the impairment LTM and the increase in the hippocampal IL-10 levels, both induced by NP. Moreover, it appears to be a safe non-pharmacological therapeutic tool since it did not alter LTM and neurochemical parameters in naive animals.

Static Magnetic Stimulation Induces Changes in the Oxidative Status and Cell Viability Parameters in a Primary Culture Model of Astrocytes.

Astrocytes play an important role in the central nervous system function and may contribute to brain plasticity response during static magnetic fields (SMF) brain therapy. However, most studies evaluate SMF stimulation in brain plasticity while few studies evaluate the consequences of SMF at the cellular level. Thus, we here evaluate the effects of SMF at 305 mT (medium-intensity) in a primary culture of healthy/normal cortical astrocytes obtained from neonatal (1 to 2-day-old) Wistar rats. After reaching confluence, cells were daily subjected to SMF stimulation for 5 min, 15 min, 30 min, and 40 min during 7 consecutive days. Oxidative stress parameters, cell cycle, cell viability, and mitochondrial function were analyzed. The antioxidant capacity was reduced in groups stimulated for 5 and 40 min. Although no difference was observed in the enzymatic activity of superoxide dismutase and catalase or the total thiol content, lipid peroxidation was increased in all stimulated groups. The cell cycle was changed after 40 min of SMF stimulation while 15, 30, and 40 min led cells to death by necrosis. Mitochondrial function was reduced after SMF stimulation, although imaging analysis did not reveal substantial changes in the mitochondrial network. Results mainly revealed that SMF compromised healthy astrocytes' oxidative status and viability. This finding reveals how important is to understand the SMF stimulation at the cellular level since this therapeutic approach has been largely used against neurological and psychiatric diseases.

Dyspnea perception during the inspiratory resistive loads test in obese subjects waiting bariatric surgery.

Identification of low dyspnea perception is relevant, since this condition is significantly associated with worse outcomes. We investigated dyspnea perception during the inspiratory resistive loads test on obese subjects waiting bariatric surgery in comparison with normal subjects. Secondarily, we analysed the proportion of obese subjects with low, moderate and high dyspnea perception. This observational study included subjects with body mass index (BMI) ≥ 35 kg/m2, compared to healthy subjects with BMI ≥ 18 and <25 kg/m2. Subject underwent clinical evaluation, inspiratory test with progressive resistive loads and spirometry. We studied 23 obese subjects (mean BMI = 51.9 ± 9.3 kg/m2) and 25 normal subjects (mean BMI = 24.3 ± 2.3 kg/m2). With the increase magnitude of resistive loads there was a significant increase in dyspnea score (p < 0.001) and progressive increase of the generated inspiratory pressure (p < 0.001), but there was no difference between the groups in terms of dyspnea score (p = 0.191) and no interaction effect (p = 0.372). Among the obese subjects, 4 individuals were classified as low perception, 11 as moderate and 8 as high. In conclusion, the degree of dyspnea perception during the inspiratory progressive resistive loads test did not differ between obese and normal subjects. Among obese subjects, only 17% were classified as low dyspnea perception.

Entraining effects of variations in light spectral composition on the rest-activity rhythm of a nocturnal rodent.

The ability to predict and adjust physiology and behavior to recurring environmental events has been necessary for survival on Earth. Recent discoveries revealed that not only changes in irradiance but also light spectral composition can stimulate the suprachiasmatic nucleus (SCN), ensuring the body's synchronization to the environment. Therefore, using a lighting system that modulates spectral composition during the day using combined red-green-blue (RGB) lights, we evaluated the effect of variations in light spectral composition on the rest-activity rhythm of rodents. Male Wistar rats (n = 17) were gestated and raised under different lighting conditions and exposed to a long photoperiod (16 h light: 8 h dark). The difference between groups was the presence of variations in light spectral composition during the day (RGB-v) to simulate daily changes in natural light, or not (RGB-f). After weaning, spontaneous motor activity was recorded continuously for rhythm evaluation. Our results indicated that animals under RGB-v did not present a reactive peak of activity after the beginning of the light phase, suggesting that this group successfully detected the variations aimed at mimicking daily alterations of natural light. Furthermore, RGB-v animals exhibited an earlier activity acrophase in comparison to animals under RGB-f (RGB-v = 12:16 - "hh:mm", RGB-f = 13:02; p < 0.001), which might have been due to the capability to predict the beginning of the dark phase when exposed to variations in light spectrum. However, this earlier activity acrophase can be also explained by the blue-light peak that occurred in RGB-v. The spectral and waveform analysis of daily patterns of motor activity revealed that rats in the RGB-v group were better entrained to a circadian rhythm throughout the experiment. RGB-v showed higher interdaily stability (IS) values (29.75 ± 6.5, n = 9) than did RGB-f (t(15)  =  2.74, p  =  0.015). Besides, the highest power content (PC) on the first harmonic (circadian) was reached earlier in the RGB-v group. The circadianity index (CI) of the whole period was higher in the RGB-v group (t(15)  =  3.47, p = 0.003). Thus, we could consider that locomotor activity rhythm was entrained to the light-dark cycle in the RGB-v rats earlier compared to the RGB-f rats. Our results provide additional evidence for the effect of variations in light spectral composition on the rest-activity pattern of nocturnal rodents. This suggests that these animals might predict the arrival of the activity phase by its advanced acrophase when exposed to RGB-v, demonstrating a better synchronization to a 24-h rhythm.

Polydimethylsiloxane/nano calcium phosphate composite tracheal stents: Mechanical and physiological properties.

In this study, we report the production and characterization of tracheal stents composed of polydimethylsiloxane/nanostructured calcium phosphate composites obtained by reactive synthesis. Tracheal stents were produced by transfer molding, and in vivo tests were carried out. PDMS was combined with H3 PO4 and Ca(OH)2 via an in situ reaction to obtain nanoparticles of calcium phosphate dispersed within the polymeric matrix. The incorporation of bioactive inorganic substances, such as calcium phosphates, improved biological properties, and the in situ reaction allowed tight coupling of particles to the matrix. Results showed the presence of the nanoparticles of DCPA and CDHA. The porosity generated during mixing decreased the tensile strength and tear properties. Composites presented higher values of cell viability compared with those for PDMS. In vivo tests indicated the presence of inflammatory tissue 30 days after implantation in both cases. Thus, the present biomaterial shows potential for application in tracheal disease, however further evaluation is needed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 545-553, 2019.

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.

Transforming growth factor beta1 (TGF-ß1) levels in a rat model of induced pleural empyema.

PURPOSE: To evaluate the concentration of transforming growth factor beta 1 (TGFB1) levels in a rat pleural effusion obtained by inoculation of intrapleural bacteria or turpentine through thoracentesis. METHODS: Thirty-Nine Wistar rats were divided into three groups: Staphylococcus aureus (SA, n = 17); Streptococcus pneumoniae (SP, n = 12); and turpentine (control, n = 10). Pleural fluid was collected through ultrasound-guided thoracentesis 12 h, 24 h, and 36 h after instillation of bacteria or turpentine. Levels of TGFB1 were measured in pleural fluid. RESULTS: At 12 h, mean TGFB1concentrations were 5.3450 pg/mL in the SA group, 5.3449 pg/mL in the SP group, and 5.3450 pg/mL in controls. At 24 h, they were 4.6700 pg/mL in the SA group, 4.6700 pg/mL in the SP group, and 4.6700 pg/mL in controls. At 36 h, they were 4.6699 pg/mL in the SA group and in control. No difference was observed among the groups in mean TGFB1concentration (p = 0.12); however, a significant intragroup reduction in mean TGFB1 was observed between 12 and 24 h (p < 0.01). CONCLUSION: The transforming growth factor beta 1 concentrations were not useful as a diagnostic tool or an early marker of infected pleural effusion.

Transcranial direct current stimulation (tDCS) prevents chronic stress-induced hyperalgesia in rats.

BACKGROUND: Chronic stress (CS) is associated with a decrease in pain threshold caused by the changes in neural pain circuits. It can be associated to glucocorticoid imbalance with alterations in neural circuitry. Inhibition of stress-induced pain-related neural changes by using techniques that safely induce neuroplasticity such as transcranial direct current stimulation (tDCS) may prevent hyperalgesia triggered by CS. OBJECTIVE: This study aimed to verify the effect of tDCS performed prior to CS exposure on nociceptive response. METHODS: Thirty-two rats were distributed in the following groups: control; stress; sham-tDCS + stress; and tDCS + stress. Bicephalic active tDCS was performed for 8 consecutive days before the CS exposure. The pain threshold was evaluated using a hot plate and tail flick latency (TFL) tests. RESULTS: The tDCS exposure increased the pain threshold on stressed rats. CONCLUSION: The data obtained indicate that the treatment with bicephalic active tDCS before chronic stress exposure prevents stress-induced hyperalgesia.

Fiber-reinforced silicone for tracheobronchial stents: An experimental study.

A trachea is a tubular structure composed of smooth muscle that is reinforced with cartilage rings. Some diseases can cause sagging in smooth muscle and cartilaginous tissue. The end result is reduction (narrowing) of the trachea diameter. A solution to this problem is the use of tracheal stents, which are small tubular devices made of silicone. One is inserted into the trachea to prevent or correct its constriction. The purpose of tracheal stent use is to maintain cartilage support that would otherwise be lost in the airway. Current tracheal stent models present limitations in terms of shape and characteristics of the silicone used in their production. One of the most important is the large thickness of the wall, which makes its placement difficult; this mainly applies to pediatric patients. The wall thickness of the stent is closely related to the mechanical properties of the material. This study aims to test the reinforcement of silicone with three kinds of fibers, and then stents that were produced using fiber with the best compressive strength characteristics. Silicone samples were reinforced with polypropylene (PP), polyamide (PA), and carbon fiber (CF) at concentrations of 2% and 4% (vol%), which then underwent tensile strength and Shore A hardness testing. Samples with fiber showed good characteristics; surface analyses were carried out and they were used to produce stents with an internal diameter of 11 or 13mm and a length of 50mm. Stents underwent compression tests for qualitative evaluation. Samples with 2% and 4% CF blends showed the best mechanical performance, and they were used to produce stents. These samples presented similar compressive strengths at low deformation, but stents with a 4% CF blend exhibited improved compressive strength at deformations greater than 30-50% of their diameter (P ≤ 0.05). The addition of 2% and 4% CF blends conferred greater mechanical strength and resistance to the silicone matrix. This is particularly true at low deformation, which is the condition where the stent is used when implanted. In the finite element compression strength tests, the stent composite showed greater compression strength with the addition of fiber, and the results were in accordance with mechanical compression tests performed on the stents. In vivo tests showed that, after 30 days of post-implantation in sheep trachea, an inflammatory process occurred in the region of the trachea in contact with the stent composite and with the stent without fiber (WF). This response is a common process during the first few days of implantation.

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.

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

INTRODUCTION: Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. OBJECTIVE: Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. METHODS: Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. RESULTS: The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). CONCLUSION: tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations.

Variability of the perception of dyspnea in healthy subjects assessed through inspiratory resistive loading.

OBJECTIVE: Few studies have evaluated the variability of the perception of dyspnea in healthy subjects. The objective of this study was to evaluate the variability of the perception of dyspnea in healthy subjects during breathing against increasing inspiratory resistive loads, as well as to assess the association between the level of perception of dyspnea and the level of physical activity. METHODS: This was a cross-sectional study involving healthy individuals 16 years of age or older. Subjects underwent inspiratory resistive loading testing, in which the level of perception of dyspnea was quantified with the modified Borg scale. We also determined body mass indices (BMIs), assessed maximal respiratory pressures, performed pulmonary function tests, applied the international physical activity questionnaire (IPAQ)-long form, and conducted six-minute walk tests (6 MWTs). The level of perception of dyspnea was classified as low (Borg score < 2), intermediate (Borg score, 2-5), or high (Borg score > 5). RESULTS: We included 48 healthy subjects in the study. Forty-two subjects completed the test up to a load of 46.7 cmH2O/L/s. The level of perception of dyspnea was classified as low, intermediate, and high in 13, 19, and 10 subjects, respectively. The level of perception of dyspnea was not significantly associated with age, gender, BMI, IPAQ-long form score, maximal respiratory pressures, or pulmonary function test results. CONCLUSIONS: The scores for perceived dyspnea induced by inspiratory resistive loading in healthy subjects presented wide variability. The perception of dyspnea was classified as low in 31% of the subjects, intermediate in 45%, and high in 24%. There was no association between the level of perception of dyspnea and the level of physical activity (IPAQ or six-minute walk distance).

Oxygen desaturation during the six-minute walk test in COPD patients.

OBJECTIVE: To evaluate the behavior of oxygen saturation curves throughout the six-minute walk test (6MWT) in patients with COPD. METHODS: We included 85 patients, all of whom underwent spirometry and were classified as having moderate COPD (modCOPD, n = 30) or severe COPD (sevCOPD, n = 55). All of the patients performed a 6MWT, in a 27-m corridor with continuous SpO2 and HR monitoring by telemetry. We studied the SpO2 curves in order to determine the time to a 4% decrease in SpO2, the time to the minimum SpO2 (Tmin), and the post-6MWT time to return to the initial SpO2, the last designated recovery time (RT). For each of those curves, we calculated the slope. RESULTS: The mean age in the modCOPD and sevCOPD groups was 66 ± 10 years and 62 ± 11 years, respectively. At baseline, SpO2 was > 94% in all of the patients; none received supplemental oxygen during the 6MWT; and none of the tests were interrupted. The six-minute walk distance did not differ significantly between the groups. The SpO2 values were lowest in the sevCOPD group. There was no difference between the groups regarding RT. In 71% and 63% of the sevCOPD and modCOPD group patients, respectively, a ≥ 4% decrease in SpO2 occurred within the first minute. We found that FEV1% correlated significantly with the ΔSpO2 (r = -0.398; p < 0.001), Tmin (r = -0.449; p < 0.001), and minimum SpO2 (r = 0.356; p < 0.005). CONCLUSIONS: In the sevCOPD group, in comparison with the modCOPD group, SpO2 was lower and the Tmin was greater, suggesting a worse prognosis in the former.

Effects of diaphragmatic contraction on lower limb venous return and central hemodynamic parameters contrasting healthy subjects versus heart failure patients at rest and during exercise.

The main objective was to assess the effects of abdominal breathing (AB) versus subject's own breathing on femoral venous blood flow (Qfv) and their repercussions on central hemodynamics at rest and during exercise contrasting healthy subjects versus heart failure (HF) patients. We measured esophageal and gastric pressure (PGA), Qfv and parameters of central hemodynamics in eight healthy subjects and nine HF patients, under four conditions: subject's own breathing and AB ( ∆: PGA ≥ 6 cmH2O) at rest and during knee extension exercises (15% of 1 repetition maximum) until exhaustion. Qfv and parameters of central hemodynamics [stroke volume (SV), cardiac output (CO)] were measured using Doppler ultrasound and impedance cardiography, respectively. At rest, healthy subjects Qfv, SV, and CO were higher during AB than subject's breathing (0.11 ± 0.02 vs. 0.06 ± 0.00 L·min(-1), 58.7 ± 3.4 vs. 50.1 ± 4.1 mL and 4.4 ± 0.2 vs. 3.8 ± 0.1 L·min(-1), respectively, P ≤ 0.05). ∆SV correlated with ∆PGA during AB (r = 0.89, P ≤ 0.05). This same pattern of findings induced by AB was observed during exercise (SV: 71.1 ± 4.1 vs. 65.5 ± 4.1 mL and CO: 6.3 ± 0.4 vs. 5.2 ± 0.4 L·min(-1); P ≤ 0.05); however, Qfv did not reach statistical significance. The HF group tended to increase their Qfv during AB (0.09 ± 0.01 vs. 0.07 ± 0.03 L·min(-1), P = 0.09). On the other hand, unlike the healthy subjects, AB did not improve SV or CO neither at rest nor during exercise (P > 0.05). In healthy subjects, abdominal pump modulated venous return improved SV and CO at rest and during exercise. In HF patients, with elevated right atrial and vena caval system pressures, these findings were not observed.