Transcranial direct current stimulation in patients with anxiety : current perspectives

Anxiety is one of the most prevalent and debilitating psychiatric conditions worldwide. Pharmaco- and psycho-therapies have been employed in the treatment of human anxiety to date. Yet, either alone or in combination, unsatisfactory patient outcomes are prevalent, resulting in a considerable number of people whose symptoms fail to respond to conventional therapies with symptoms remaining after intervention. The demand for new therapies has given birth to several noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) has arisen as a promising tool and has been proven to be safe and well tolerated for the treatment of many diseases, including chronic pain, depression, and anxiety. Here, reports of the use of tDCS in anxiety disorders in human patients were reviewed and summarized. A literature search was conducted in mid-2019, to identify clinical studies that evaluated the use of tDCS for the treatment of anxiety behavior. The PubMed, Web of Science, and Scielo and PsycInfo databases were explored using the following descriptors: “anxiety”, “anxious behavior”, “tDCS”, and “transcranial direct current stimulation”. Among the selected articles, considerable variability in the type of tDCS treatment applied in interventions was observed. Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combination with others

Farmacoterapia da obesidade: Benefícios e Riscos

The growing number of obese people during the past decades, makes obesity a public health matter. It is considered a disease caused by multiple factors and dependent on genetic interaction, metabolic, social, behavioral and cultural factors. Pharmacologic therapy is recommended as an adjuvant therapy for obese patients or those who are overweight, which may be associated with co-morbidities putting their lives at risk. The anti obesity drugs generally act by decreasing appetite, fat absorption by inhibiting or increasing the thermogenesis and energy consumption and also in neurotransmitter systems. Among the drugs used as diet pills, we can highlight: Sibutramine, Amfepramone, Orlistat, Caffeine, Garcinia Cambogia. Therefore, the object of this systematic literature review is to check the main classes of drugs used for weight loss, that are released for the marketing in the Brazilian pharmaceutical market, highlighting its risks and benefits. The benefits of the use of pharmacological agents is to promote increased patients adherence to dietary behavioral changes and, weight loss. However, it is important to note that all the pharmacological therapy is accompanied by adverse effects and, that these effects can put the patients’ health at risk, herbal medicines as well. The use and abuse of these drugs are very common and widespread in our society, therefore, emphasizes the importance of correct information on this topic and the fundamental role of the pharmacist on guidance for the use of these drugs.O crescente aumento no número de pessoas obesas, nas últimas décadas, torna a obesidade um problema de saúde pública. É considerada uma doença de causa multifatorial e dependente da interação de fatores genéticos, metabólicos, sociais, comportamentais e culturais. A terapia farmacológica é recomendada como uma ferramenta adjuvante para pacientes obesos ou que apresentam sobrepeso, que podem estar associadas com co-morbidades que colocam suas vidas em risco. Os fármacos antiobesidade geralmente atuam diminuindo o apetite, inibindo absorção de gordura ou aumentando o consumo de energia e termogênese, e também em sistemas de neurotransmissão. Dentre os medicamentos utilizados como emagrecedores, podemos destacar: sibutramina, anfepramona, orlistate, cafeína, Garcinia cambogia. Para tanto, o objetivo desta presente revisão bibliográfica sistemática é verificar as principais classes de medicamentos utilizados para emagrecimento, que estão liberados para a comercialização no mercado brasileiro, destacando seus riscos e benefícios. O uso e abuso destes medicamentos é muito comum e difundido na nossa sociedade, portanto, ressalta-se a importância da correta informação sobre este tema

A3 receptor agonist modulates IL-1β hippocampus levels in a rat model of neuropathic pain

Introduction: Considering the lack of specific treatments for neuropathic pain, this study aimed to evaluate the effect of a single dose of adenosine A3 receptor IB-MECA on inflammatory and neurotrophic parameters in rats subjected to a neuropathic pain model. Methods: 64 adult male Wistar rats were used. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve and the treatment consisted of a 0.5 μmol/kg dose of IB-MECA, a selective A3 adenosine receptor agonist, dissolved in 3% DMSO; vehicle groups received DMSO 3% in saline solution, and morphine groups received 5 mg/kg. Cerebral cortex and hippocampus IL-1β, BDNF, and NGF levels were determined by Enzyme-Linked Immunosorbent assay. Results: The main outcome was that a single dose of IB-MECA was able to modulate the IL-1β hippocampal levels in neuropathic pain induced by CCI and the DMSO increased IL-1β and NGF hippocampal levels in sham-operated rats. However, we did not observe this effect when the DMSO was used as vehicle for IB-MECA, indicating that IB-MECA was able to prevent the effect of DMSO. Conclusions: Considering that the IL-1β role in neuropathic pain and the contributions of the hippocampus are well explored, our result corroborates the relationship between the A3 receptor and the process of chronic pain maintenance

Different Intensities of Treadmill Running Exercise do Not Alter Melatonin Levels in Rats

Background: Regular and moderate exercise has been considered an interesting neuroprotective strategy. Our research group demonstrated that a protocol of moderate exercise on a treadmill reduced, while a protocol of high-intensity exercise increased in vitro ischemic cell damage in Wistar rats. The molecular mechanisms by which physical exercise exerts neuroprotective effects remain unclear. Accumulating evidence suggests that exercise may have short- and long-term effects on melatonin secretion in humans. Melatonin, the main product of the pineal gland, has been shown to have neuroprotective effects in models of brain and spinal cord injury and cerebral ischemia. A dual modulation of melatonin secretion by physical activity has also been demonstrated. This study aimed to investigate the effect of different exercise intensities, moderate- and high-intensity exercise, on serum melatonin levels in rats. Methods: Thirty-five adult male Wistar rats were divided into non-exercised (sedentary) and exercised (20- or 60-min sessions) groups. The exercise protocols consisted of two weeks of daily treadmill training. Blood samples were collected approximately 16 hours after the last training session (8:00-10:00) and melatonin levels were assayed by ELISA.Results: The exercise protocols, two weeks of 20 min/day or 60 min/day of treadmill running, did not affect serum melatonin levels.Conclusion: Our data demonstrated that melatonin levels may not be directly involved in the exercise-induced, intensity-dependent dual effect on in vitro ischemia

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

AbstractTranscranial 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

A3 receptor agonist modulates IL-1β hippocampus levels in a rat model of neuropathic pain

Introduction: Considering the lack of specific treatments to neuropathic pain, this study aimed to evaluate the effect of a single dose adenosine A3 receptor IB-MECA in the inflammatory and neurotrophic parameters of rats submitted to a neuropathic pain model. Methods: 64 adults male Wistar rats were used.  Neuropathic pain was induced by the chronic constriction injury (CCI) of sciatic nerve and the treatment consisted in one dose of 0.5 μmol/kg of a selective agonist of adenosine A3 receptor IB-MECA dissolved in 3% DMSO; vehicle groups received DMSO 3% in saline; morphine groups received 5mg/kg Cerebral cortex and hippocampus IL-1β, BDNF and NGF levels were determined by ELISA assay. Results: The key finding was that a single dose of IB-MECA was able to modulate the IL-1β hippocampus levels CCI and the DMSO increased IL-1β and NGF hippocampus levels in sham animals; however, when the DMSO as an IB-MECA vehicle, this effect was not observed, indicating that IB-MECA was able to prevent the effect of DMSO. Conclusions: Considering that the IL-1β role in neuropathic pain is quite explored, as well as the hippocampus contributions, our result corroborates the relationship of A3 receptor and the chronic pain maintenance process. @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman",serif; mso-fareast-font-family:"Times New Roman";}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes;}div.WordSection1 {page:WordSection1;

Effects of restraint stress on the daily rhythm of hydrolysis of adenine nucleotides in rat serum

<p>Abstract</p> <p>Background</p> <p>Adenosine 5-triphosphate (ATP) and its breakdown products ADP and adenosine can act as extracellular messengers in a range of biological processes. Extracellular adenine nucleotides are metabolized by a number of enzymes including NTPDases and 5'-nucleotidase, which are considered to be the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATPase and ADPase activities in rat serum exhibit a 24-h temporal pattern, with higher enzyme activity during the dark (activity) phase. It was found that stress can cause disruptions in biological circadian rhythms and in the cardiovascular system. Therefore, the aim of the present study was to examine the influence of acute stress exposure upon temporal patterns of NTPDase and 5-nucleotidase enzyme activities in rat blood serum.</p> <p>Methods</p> <p>Adult male Wistar rats were divided into 4 groups: ZT0, ZT6, ZT12 and ZT18. Each group was subdivided in 4 groups: control, immediately, 6 h and 24 h after one hour of restraint stress. ATP, ADP and AMP hydrolysis were assayed in the serum.</p> <p>Results</p> <p>All stressed groups showed significant decreases in all enzyme activities at ZT 12 and ZT 18 when compared with control.</p> <p>Conclusion</p> <p>Acute stress provokes a decrease in nucleotidase activities dependent on the time that this stress occurs and this effect appears to persist for at least 24 hours. Stress can change levels of nucleotides, related to increased frequency of cardiovascular events during the activity phase. Altered levels of nucleotides in serum may be involved in cardiovascular events more frequent during the activity phase in mammals, and with their etiology linked to stress.</p

Transcranial direct current stimulation combined with exercise modulates the inflammatory profile and hyperalgesic response in rats subjected to a neuropathic pain model : long-term effects

Background: Behavioral alterations, like mechanical and thermal hyperalgesia, and modulation of biomarkers in the peripheral and central nervous systems (CNS) are markers of chronic pain. Transcranial direct current stimulation (tDCS) with exercise is a promising therapy for pain due to its neuromodulatory capacity. Objective: To assess the individual effects of tDCS, exercise, and the two combined on the nociceptive response and BDNF, IL-1b, and IL-4 levels in the CNS structures of rats in a chronic pain model. Methods: For 8 consecutive days after the establishment of chronic neuropathic pain by inducing a constriction injury to the sciatic nerve (CCI), the rats received tDCS, exercise, or both treatments combined (20 min/day). The hyperalgesic response was assessed by von Frey and hot plate tests at baseline, 7, and 14 days after CCI surgery and immediately, 24 h, and 7 days after the end of treatment. The BDNF, IL1b, and IL-4 levels were assessed in the cerebral cortex, brainstem, and spinal cord by enzyme-linked immunosorbent assay at 48 h and 7 days after the end of treatment. Results: The CCI model triggered marked mechanical and thermal hyperalgesia. However, bimodal tDCS, aerobic exercise, and the two combined relieved nociceptive behavior for up to 7 days following treatment completion. Conclusions: Bimodal tDCS, aerobic exercise, or both treatments combined promoted analgesic effects for neuropathic pain. Such effects were reflected by cytokine modulation throughout the spinal cordbrainstem-cerebral cortex axis