Gabriela Laste

Reversal of chronic stress-induced pain by transcranial direct current stimulation (tDCS) in an animal model.

Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1β levels in serum and TNFα levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). Forty-one adult male Wistar rats were divided into two groups control and stress. The stress group was exposed to CRS for 11 weeks for the establishment of hyperalgesia and mechanical allodynia as shown by the hot plate and von Frey tests, respectively. Rats were then divided into four groups control, stress, stress+sham tDCS and stress+tDCS. Anodal or sham tDCS was applied for 20min/day over 8 days and the tests were repeated. Then, the animals were killed, blood collected and hippocampus removed for ELISA testing. This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNFα levels. These results support the notion that tDCS reverses the detrimental effects of chronic stress on the pain system and decreases TNFα levels in the hippocampus.

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.

Prevalência de morbidades e sintomas em idosos: um estudo comparativo entre zonas rural e urbana

Realizou-se um estudo transversal, com a populacao idosa moradora nas zonas rural e urbana caracterizando a prevalencia de morbidades e sintomas. Entrevistou-se 229 idosos, com media de idade de 72,3 anos, 57,2% residem na zona urbana, 56,3% sao do sexo feminino. As morbidades mais relatadas por residentes da zona urbana foram: insonia (37,7%), ansiedade (32,1%), depressao (26,7%); e na rural, diabetes (13,3%). Nesta, a Doenca de Alzheimer foi mais prevalente em idosos que utilizam agrotoxicos (21,7%). Os sintomas mais prevalentes por moradores da zona urbana foram: tosse/coriza e visao alterada (41,2%), alergia/coceira (11,4%). Na rural, boca seca (25,4%), visao alterada (35,6%) e dor nas pernas (66,1%) que tambem foram mais prevalentes em quem utilizava agrotoxicos. O uso de Equipamentos de Protecao Individual de forma incompleta foi de 85,4% e 45,1% descartam as embalagens de forma inadequada. Ha a necessidade de desenvolvimento de programas de saude publica que auxiliem na promocao de saude do idoso, e que considere a possivel exposicao dessa populacao a agrotoxicos com um determinante em saude.

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.

Melatonin administration reduces inflammatory pain in rats

In view of the broad range of effects attributed to melatonin, this study evaluated its analgesic effect on inflammatory pain induced by complete Freund’s adjuvant (CFA) in Wistar rats. Inflammation was induced by intradermal CFA injection in the hind paw of all animals, which were then divided into two groups that received either 60 mg/kg of melatonin or vehicle (1% alcohol in saline), intraperitoneally, for three days. The analgesic effect of melatonin was assessed by the hot-plate test, immediately and thereafter at 30, 60, 90, and 120 minutes after the first administration and 24 hours after once-daily administration for 2 more days. After CFA injection, melatonin administration increased withdrawal latency at 60 minutes after the first dose. After the end of treatment, melatonin showed a significant analgesic effect on inflammatory pain. This study paves the way for exploration of how brief courses of treatment could improve this analgesic effect in the late phases of inflammatory pain.

The prevalence of morbidity and symptoms among the elderly: a comparative study between rural and urban areas

A cross-sectional study was conducted with the elderly population in rural and urban areas characterized by the prevalence of morbidity and symptoms, and 229 elderly people were interviewed. The average age was 72.3, of which 57.2% lived in the rural zone and 56.3% were female. The morbidities most reported were insomnia (37.7%), anxiety (32.1%), depression (26.7%), and in the rural zone it was diabetes (13.3%). In this zone, Alzheimers disease was more prevalent among the elderly who handled pesticides (21.7%). The most prevalent symptoms among urban zone residents were: cough/runny nose and sight alterations (41.2%), allergy/itching (11.4%). In the rural zone, dry mouth (25.4%), sight alterations (35.6%) and leg pain (66.1%) were also more prevalent among those who used pesticides. The inadequate use of Individual Protection Equipment was 85.4%, and 45.1% also disposed of pesticide packaging inappropriately. The setting up of public health programs is necessary to promote health among the elderly and the potential exposure to pesticides for this population should be seen as a health risk determinant.

Protracted alcohol abstinence induces analgesia in rats: Possible relationships with BDNF and interleukin-10

Exposure to ethanol alters the expression of brain-derived neurotrophic factor (BDNF) in central regions such as, the hippocampus, cortex and striatum. Moreover, chronic alcohol intake is known to induce selective neuronal damage associated with an increase in the inflammatory cascade, resulting in neuronal apoptosis and neurodegeneration. In the present study, we investigated the nociceptive response after 24h of protracted alcohol abstinence. Rats were submitted to a model of alcohol withdrawal syndrome and the nociceptive response was assessed by the tail-flick and the hot plate tests. In addition, we evaluated BDNF and interleukin-10 (IL-10) in the cerebral prefrontal cortex, brainstem and hippocampus of rats after protracted alcohol abstinence. Male adult Wistar rats were divided into three groups: non-treated group (control group), treated with water (water group), and alcohol (alcohol group). The water and alcohol administrations were done by oral gavage and were performed over three periods of five days of treatment with two intervals of two days between them. Alcohol (20%w/v) was given at 4g/kg of body weight. There was a significant effect of treatment in the tail-flick and hot plate latencies with greater latencies in alcohol-treated rats after 10days of abstinence. There was a significant increase in the prefrontal cortex BDNF levels in the alcohol group in relation to the water group, after 11days of alcohol abstinence. In addition, alcohol withdrawal induced a significant increase in the hippocampus, prefrontal cortex and brainstem IL-10 levels compared with control group. Thus, the present study demonstrates that protracted alcohol withdrawal produced an analgesic effect indexed via increased nociceptive threshold. We suggest that these effects could be related to the increased levels of BDNF and IL-10 observed in the central nervous system.

Morphine treatment in early life alters glutamate uptake in the spinal synaptosomes of adult rats.

Morphine exposure during the neonatal period can promote changes in pain signaling pathways that can be expressed as an increased nociceptive response in adult life. Glutamate is the major excitatory neurotransmitter in primary afferent terminals and plays a critical role in normal spinal excitatory synaptic transmission. Considering the importance of a better understanding of the mechanisms that underlie nociceptive changes throughout the life course, the aim of this study was investigate the effects of repeated morphine administration at postnatal days 8 (P8) to 14 (P14) on glutamate uptake in spinal synaptosomes at P30 and P60. The morphine group showed decreased [3H]-glutamate uptake as compared to control groups in both P30 and P60. These findings suggest that morphine exposure in early life leads to changes in glutamatergic signaling at least until the 60th day of age, which may lead to increased levels of glutamate in the spinal synaptic cleft and, consequently, an increased nociceptive response in adult life. Thus, this study highlights the importance of conducting research in this field to provide a comprehensive knowledge of the long-term effects of early-life morphine treatment on nociceptive pathways.

Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation.

Transcranial direct current stimulation (tDCS) and melatonin can effectively treat pain. Given their potentially complementary mechanisms of action, their combination could have a synergistic effect. Thus, we tested the hypothesis that compared to the control condition and melatonin alone, tDCS combined with melatonin would have a greater effect on pain modulatory effect, as assessed by quantitative sensory testing (QST) and by the pain level during the Conditioned Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a greater cortical excitability effect as indicated by the transcranial magnetic stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18–40 years), in a blinded, placebo-controlled, crossover, clinical trial, were randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS, melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS. Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex. There was a significant difference in the heat pain threshold (°C) for melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16, 95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and melatonin+a-tDCS (mean difference: 0.29, 95% CI: −3.72 to 4.23). The mean change from the baseline on amplitude of motor evocate potential (MEP) was significantly higher in the melatonin+a-tDCS (−19.96% ± 5.2) compared with melatonin+s-tDCS group (−1.36% ± 5.35) and with placebo+s-tDCS group (3.61% ± 10.48), respectively (p < 0.05 for both comparisons). While melatonin alone or combined with a-tDCS did not significantly affect CPM task result, and serum BDNF level. The melatonin effectively reduced pain; however, its association with a-tDCS did not present an additional modulatory effect on acute induced pain.

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.