Effects of melatonin and estradiol on chronic pain during postmenopause

Chronic pain is a major public health problem that affects approximately 40% of the adult population worldwide. Several epidemiological studies have shown a higher prevalence of chronic pain in women, with variation within the menstrual cycle and worsening after menopause. Clinical and experimental studies have shown differences in pain perception between genders, but the underlying mechanisms of this inequality are complex and far from being understood. Estrogens play an important role in pain modulation and seem to account, at least in part, for these differences. Melatonin is a neurohormone synthesized mainly by the pineal gland that regulates circadian rhythms and has anti-inflammatory, antioxidant, sedative, antidepressant, anxiolytic, and analgesic effects. After menopause, melatonin levels decrease, which may cause the sleep disorders that usually affect women during this period of life. Some studies have demonstrated an interaction between melatonin and estrogens in terms of antioxidant effects. The present study seeks to provide a review on melatonin, estradiol, and chronic pain in women

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

Effects of melatonin and estradiol on chronic pain during postmenopause

Chronic pain is a major public health problem that affects approximately 40% of the adult population worldwide. Several epidemiological studies have shown a higher prevalence of chronic pain in women, with variation within the menstrual cycle and worsening after menopause. Clinical and experimental studies have shown differences in pain perception between genders, but the underlying mechanisms of this inequality are complex and far from being understood. Estrogens play an important role in pain modulation and seem to account, at least in part, for these differences. Melatonin is a neurohormone synthesized mainly by the pineal gland that regulates circadian rhythms and has anti-inflammatory, antioxidant, sedative, antidepressant, anxiolytic, and analgesic effects. After menopause, melatonin levels decrease, which may cause the sleep disorders that usually affect women during this period of life. Some studies have demonstrated an interaction between melatonin and estrogens in terms of antioxidant effects. The present study seeks to provide a review on melatonin, estradiol, and chronic pain in women

The mapping of cortical activation by near infra-red spectroscopy might be a biomarker related to the severity of fibromyalgia

The delta value of oxyhemoglobin (Δ-HbO) determined by functional near-infrared spectroscopy at prefrontal cortex (PFC) and motor cortex (MC) based on primary (25 °C) and secondary (5 °C) thermal stimuli presented a larger peak latency at left MC in fibromyalgia than in controls. The difference between HbO concentration 15 s after the thermal stimuli ending and HbO concentration before the thermal stimuli onset (Δ-HbO*) at left PFC increased 47.82% in fibromyalgia and 76.66% in controls. This value had satisfactory discriminatory properties to differentiate cortical activation in fibromyalgia versus controls. A receiver operator characteristics (ROC) analysis showed the Δ-HbO* cutoffs of − 0.175 at left PFC and − 0.205 at right PFC offer sensitivity and specificity of at least 80% in screening fibromyalgia from controls. In fibromyalgia, a ROC analysis showed that these cutoffs could discriminate those with higher disability due to pain and more severe central sensitization symptoms (CSS). The ROC with the best discriminatory profile was the CSS score with the Δ-HbO* at left PFC (area under the curve = 0.82, 95% confidence interval = 0.61–100). These results indicate that cortical activation based on Δ-HbO* at left PFC might be a sensitive marker to identify fibromyalgia subjects with more severe clinical symptoms

Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity

Objective: This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00–12:00 hours), afternoon (12:00–18:00 hours), evening (18:00–24:00 hours), and night (24:00–06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT). Patients and methods: We included 54 women, aged 18–60 years with diagnosis of FM (n=18), MDD (n=19), and HC (n =17). The 24-hour urinary aMT6s was evaluated according to four standardized periods. The assessment instruments were the Hamilton Depression Rating Scale (HDRS), Pittsburgh Sleep Quality Index, and Fibromyalgia Impact Questionnaire Results: A generalized estimating equation revealed no difference in the daily load of aMT6s secretion among the three groups (P=0.49). However, at the daily time (06:00–18:00 hours), the load secretion of aMT6s reached 41.54% and 60.71% in the FM and MDD, respectively, as compared to 20.73% in the HC (P<0.05). A higher score in the HDRS was positively correlated with the amount of aMT6s secretion during daytime (06:00–18:00 hours). Also, multivariate linear regression revealed that in FM subjects, the aMT6s secretion during daytime (06:00–18:00 hours) was negatively correlated with the PPTlog (partial η2=0.531, P=0.001). However, it was positively correlated with depressive symptoms (partial η2=0.317, P=0.01); PQSI (partial η2=0.306, P=0.017), and NTPs (partial η2=0.23, P=0.04). Conclusion: A more significant load of aMT6s secretion during daytime hours was observed in MDD and FM subjects compared to HC. These findings help to comprehend the biological basis of these disorders and show how disruption in melatonin secretion is positively correlated with clinical symptoms

Caffeine teratogenicity in rats: morphological characterization and hypothesized mechanisms

Caffeine consumption during pregnancy has been shown in the scientific literature to be associated with teratogenicity such as low birth weight, fetal malformations, and miscarriage. However, the morphological alterations of the offspring of dams exposed during pregnancy have not been consistently described, and the mechanisms why they occur remain elusive. Thus, we aimed to characterize the offspring malformations induced by moderate and high doses of caffeine during pregnancy. Dams were divided into three groups: control, moderate (0.3 g/L), and high dose (1.0 g/L) of caffeine, which was provided in the drinking water beginning on gestational day 1 and continuing throughout the entire gestation. At moderate doses, only one of the dams had stillborn pups, although no macroscopic malformations were observed. High doses of caffeine induced significantly more malformations (P&lt;0.001) and early death (before P4). The malformations observed were related to fetal development and cardiovascular alterations, namely bruises, macrocephaly with short limbs, abnormal development (or absence) of head structures and limbs, labial malformations, hydrops fetalis, and poor placental formation. We discussed the proposed mechanisms by which caffeine might induce these phenotypes, which may involve down-regulation of adenosine A1 receptors, and increased mothers’ catecholamines. Our findings further confirm the evidence of the teratogenic effects of high doses of caffeine administered during pregnancy. These findings support the recommendation to avoid caffeine exposure during pregnancy. Keywords: Caffeine; offspring; teratogenicity; pregnancy; hydrops; cardiovascular alteration

Central post-stroke pain An intetegrative review of somatotopic damage, clinical symptoms, and neurophysiological measures

Introduction: The physiopathology of central post-stroke pain (CPSP) is poorly understood, which may contribute to the limitations of diagnostic and therapeutic advancements. Thus, the current systematic review was conducted to examine, from an integrated perspective, the cortical neurophysiological changes observed via transcranial magnetic stimulation (TMS), focusing on the structural damage, and clinical symptoms in patients with CPSP. Methods: The literature review included the databases EMBASE, PubMed, and ScienceDirect using the following search terms by MeSH or Entree descriptors: [(“Cerebral Stroke”) AND (“Pain” OR “Transcranial Magnetic Stimulation”) AND (“Transcranial Magnetic Stimulation”)] (through September 29, 2020). A total of 297 articles related to CPSP were identified. Of these, only four quantitatively recorded cortical measurements. Results: We found four studies with different methodologies and results of the TMS measures. According to the National Institutes of Health (NIH) guidelines, two studies had low methodological quality and the other two studies had satisfactory methodological quality. The four studies compared the motor threshold (MT) of the stroke-affected hemisphere with the unaffected hemisphere or with healthy controls. Two studies assessed other cortical excitability measures, such as cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). The main limitations in the interpretation of the results were the heterogeneity in parameter measurements, unknown cortical excitability measures as potential prognostic markers, the lack of a control group without pain, and the absence of consistent and validated diagnosis criteria. Conclusion: Despite the limited number of studies that prevented us from conducting a meta-analysis, the dataset of this systematic review provides evidence to improve the understanding of CPSP physiopathology. Additionally, these studies support the construction of a framework for diagnosis and will help improve the methodological quality of future research in somatosensory sequelae following stroke. Furthermore, they offer a way to integrate dysfunctional neuroplasticity markers that are indirectly assessed by neurophysiological measures with their correlated clinical symptoms

Efeitos da administração aguda de alta dose de metilprednisolona sobre órgãos de ratas Wistar

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