Peripheral body temperature rhythm as a marker of the severity of depression symptoms in fibromyalgia.

BACKGROUND: Circadian rhythm alterations have been reported in fibromyalgia (FM) and depression. Peripheral body temperature (PBT) is a reliable measure of the circadian system, so we compared the PBT rhythm between persons with FM and controls. We evaluated PBT correlation with depression symptoms and pain severity in women with FM. METHODS: We included 101 women aged 30-65 with FM diagnosis (FM group, n = 83) and controls (n = 18). Twenty-four-hour PBT was assessed by actigraphy. For the analysis, in the FM group, the PBT measurement was divided into four periods: morning (6 a.m.-noon), afternoon (noon-6 p.m.), evening (6 p.m.-midnight), and night (midnight-6 a.m.). According to their scores on the Hamilton Depression Rating Scale (HDRS), participants were classified as having mild or moderate to severe depression symptoms. RESULTS: There was no difference in PBT between FM and controls. Subjects with FM and moderate to severe depression symptoms showed a higher PBT (p = .003) during the evening period (p = .004). The analysis of PBT rhythm revealed an interaction between time and group according to mild or moderate to severe depression symptoms (χ2 (3) = 12.79, p < .005). The pain severity was positively correlated with PBT (ß=0.22, [CI 95%, 0.07-0.37], p = .003). CONCLUSIONS: PBT rhythm was not a sensitive measure for discriminating persons with FM from controls. In FM, PBT is related to the severity of depression symptoms and pain intensity.

Primary somatosensory cortex and periaqueductal gray functional connectivity as a marker of the dysfunction of the descending pain modulatory system in fibromyalgia.

Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between pain-modulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life. Methods: This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group. Results: Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63-0.94) to discriminate who does/does not respond to the CPM-test. Conclusions: These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients.

Short-term effectiveness of transcranial direct current stimulation in the nociceptive behavior of neuropathic pain rats in development.

Neuropathic pain (NP) is caused by a lesion that triggers pain chronification and central sensitization and it can develop in a different manner, dependent of age. Recent studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) for treating NP. Then, we aimed to investigate the effects of tDCS and BDNF levels in neuropathic pain rats in development, with 30 days old in the beginning of experiments. Eight-five male Wistar rats were subjected to chronic constriction injury. After establishment of NP, bimodal tDCS was applied to the rats for eight consecutive days, for 20 minutes each session. Subsequently, nociceptive behavior was assessed at baseline, 14 days after surgery, 1 day and 7 days after the end of tDCS. The rats were sacrificed 8 days after the last session of tDCS. An increase in the nociceptive threshold was observed in rats in development 1 day after the end of tDCS (short-term effect), but this effect was not maintained 7 days after the end of tDCS (long-term effect). Furthermore, brain derived neurotrophic factor (BDNF) levels were analyzed in the frontal cortex, spinal cord and serum using ELISA assays. The neuropathic pain model showed an effect of BDNF in the spinal cord of rats in development. There were no effects of BNDF levels of pain or tDCS in the frontal cortex or serum. In conclusion, tDCS is an effective technique to relieve nociceptive behavior at a short-term effect in neuropathic pain rats in development, and BDNF levels were not altered at long-term effect.

Transcranial direct current stimulation did not revert the increased central and peripheral NGF levels induced by neuropathic pain in rats / Tratamento com estimulação transcraniana por corrente contínua não reverteu o aumento de NGF induzido por modelo de dor neuropática em ratos

ABSTRACT BACKGROUND AND OBJECTIVES: The expression of nerve growth factor (NGF) in the large-size neurons may represent a key role in the neuronal synaptic plasticity and re-organization of neuronal function after a nerve injury. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising tool to pain management since it promotes neuroplasticity in the central system, and it can be combined with other interventions. The aim was to investigate the effects of tDCS in the NGF levels in central and peripheral nervous system structures of rats submitted to a neuropathic pain (NP) model. METHODS: The chronic constriction injury (CCI) of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed, but without any ligation. The control group did not undergo surgical procedure. After the establishment of NP, treated groups were subjected to tDCS treatment 0.5 mA/20min/day/8 days. NGF levels in cerebral cortex, spinal cord and sciatic nerve were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. RESULTS: The CCI model increased NGF levels in all three structures analyzed at long-lasting time, evidencing the importance of this neurotrophin in neuropathic pain condition. On the other hand, there was no tDCS effect in the central and peripheral NGF levels discarding the participation of this neurotrophin in the analgesic tDCS effect. CONCLUSION: tDCS modulation effects of nociceptive pathways seem not to be linked to the NGF signaling in this chronic pain model.

RESUMO JUSTIFICATIVA E OBJETIVOS: A expressão do fator de crescimento neural (NGF) em neurônios de diâmetro largo pode representar um papel importante na plasticidade sináptica neuronal e na reorganização da função neuronal após lesão neural. A estimulação transcraniana por corrente contínua (ETCC) é um método não invasivo de estimulação cerebral e representa uma ferramenta promissora para o manejo da dor, pois promove neuroplasticidade no sistema central, podendo ser combinada com outras intervenções. O objetivo foi investigar os efeitos da ETCC nos níveis de NGF em estruturas do sistema nervoso central e periférico de ratos submetidos a um modelo de dor neuropática (DN). MÉTODOS: A constrição crônica (CCI) do nervo isquiático foi utilizada para indução do modelo de DN. Na cirurgia sham, o nervo foi exposto, no entanto não houve constrição do nervo. O grupo controle não foi submetido ao procedimento cirúrgico. Após estabelecimento da DN, os grupos tratados foram submetidos a ETCC 0,5 mA/20min/dia/8 dias. Os níveis de NGF no córtex cerebral, medula espinal e nervo isquiático foram mensurados pela técnica de ELISA 48 horas e 7 dias após o final do tratamento. RESULTADOS: O modelo de dor CCI aumentou os níveis de NGF nas três estruturas analisadas, evidenciando a importância desta neurotrofina na dor neuropática. Por outro lado, não houve efeito da ETCC nos níveis de NGF central e periférico, descartando o papel desta neurotrofina no efeito analgésico da ETCC. CONCLUSÃO: Efeitos da ETCC sobre vias nociceptivas não estão diretamente relacionados com a sinalização do NGF neste modelo de dor crônica.

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.

Transcranial Direct Current Stimulation to Improve the Dysfunction of Descending Pain Modulatory System Related to Opioids in Chronic Non-cancer Pain: An Integrative Review of Neurobiology and Meta-Analysis.

Background: Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS). Objectives: This integrative review with meta-analysis aimed: (i) To discuss the potential mechanisms involved in analgesic tolerance and opioid-induced hyperalgesia (OIH). (ii) To examine how the opioid can affect the function of DPIS. (ii) To show evidence about the tDCS as an approach to treat acute and chronic pain. (iii) To discuss the effect of tDCS on DPIS and how it can counter-regulate the OIH. (iv) To draw perspectives for the future about the tDCS effects as an approach to improve the dysfunction in the DPIS in chronic non-cancer pain. Methods: Relevant published randomized clinical trials (RCT) comparing active (irrespective of the stimulation protocol) to sham tDCS for treating chronic non-cancer pain were identified, and risk of bias was assessed. We searched trials in PubMed, EMBASE and Cochrane trials databases. tDCS protocols accepted were application in areas of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), or occipital area. Results: Fifty-nine studies were fully reviewed, and 24 with moderate to the high-quality methodology were included. tDCS improved chronic pain with a moderate effect size [pooled standardized mean difference; -0.66; 95% confidence interval (CI) -0.91 to -0.41]. On average, active protocols led to 27.26% less pain at the end of treatment compared to sham [95% CI; 15.89-32.90%]. Protocol varied in terms of anodal or cathodal stimulation, areas of stimulation (M1 and DLPFC the most common), number of sessions (from 5 to 20) and current intensity (from 1 to 2 mA). The time of application was 20 min in 92% of protocols. Conclusion: In comparison with sham stimulation, tDCS demonstrated a superior effect in reducing chronic pain conditions. They give perspectives that the top-down neuromodulator effects of tDCS are a promising approach to improve management in refractory chronic not-cancer related pain and to enhance dysfunctional neuronal circuitries involved in the DPIS and other pain dimensions and improve pain control with a therapeutic opioid-free. However, further studies are needed to determine individualized protocols according to a biopsychosocial perspective.

Cognitive effects of transcranial direct current stimulation combined with working memory training in fibromyalgia: a randomized clinical trial.

Cognitive dysfunction in fibromyalgia has been reported, especially memory. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in enhancing this function. We tested the effects of eight sessions of tDCS and cognitive training on immediate and delayed memory, verbal fluency and working memory and its association with brain-derived neurotrophic factor (BDNF) levels. Forty females with fibromyalgia were randomized to receive eight sessions of active or sham tDCS. Anodal stimulation (2 mA) was applied over the DLPFC and online combined with a working memory training (WMT) for 20 minutes. Pre and post-treatment neurocognitive tests were administered. Data analysis on deltas considering years of education and BDNF as covariates, indicated active-tDCS + WMT significantly increased immediate memory indexed by Rey Auditory Verbal Learning Test score when compared to sham. This effect was dependent on basal BDNF levels. In addition, the model showed active stimulation increased orthographic and semantic verbal fluency scores (Controlled Oral Word Association Test) and short-term memory (Forward Digit Span). The combination of both techniques seemed to produce effects on specific cognitive functions related to short-term and long-term episodic memory and executive functions, which has clinical relevance for top-down treatment approaches in FM.

Preoperative transcranial direct current stimulation: Exploration of a novel strategy to enhance neuroplasticity before surgery to control postoperative pain. A randomized sham-controlled study.

BACKGROUND: An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS) becomes attractive. OBJECTIVE: We tested the hypothesis that two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and during walking (primary outcomes)]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task), disability related to pain (DRP) and analgesic consumption (secondary outcomes). Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP. METHODS: It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S). RESULTS: A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21) and higher function of descending pain modulatory system (DPMS) during CPM-task. CONCLUSION: A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02360462.

Anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex modulates attention and pain in fibromyalgia: randomized clinical trial.

Cognitive dysfunction in fibromyalgia patients has been reported, especially when increased attentional demands are required. Transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in modulating attention. We tested the effects of a single session of tDCS coupled with a Go/No-go task in modulating three distinct attentional networks: alertness, orienting and executive control. Secondarily, the effect on pain measures was evaluated. Forty females with fibromyalgia were randomized to receive active or sham tDCS. Anodal stimulation (1 mA, 20 min) was applied over the DLPFC. Attention indices were assessed using the Attention Network Test (ANT). Heat pain threshold (HPTh) and tolerance (HPTo) were measured. Active compared to sham tDCS led to increased performance in the orienting (mean difference [MD] = 14.63) and executive (MD = 21.00) attention networks. There was no effect on alertness. Active tDCS increased HPTh as compared to sham (MD = 1.93) and HPTo (MD = 1.52). Regression analysis showed the effect on executive attention is mostly independent of the effect on pain. DLPFC may be an important target for neurostimulation therapies in addition to the primary motor cortex for patients who do not respond adequately to neurostimulation therapies.

Evaluation of different procedure involved in the Transcranial Direct Current Stimulation (tDCS) technique experimental application

Introduction: The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in the central nervous system of animals and humans. Furthermore, tDCS has been suggested as a therapeutic tool for pain management. The aim of this study was to standardize a non-invasive tDCS technique indexed by the nociceptive response of rats submitted to different conditions necessary to the tDCS application. Method: 60-day-old male Wistar rats (n=65), divided into 6 groups: control(C); non-active sham (NAS); active-sham (AS); active-sham restrained (ASR); non-active sham restrained (NASR); active tDCS treatment. Animals received treatment during 30 seconds (sham-active) or 20 minutes (restraint and tDCS)/8 days. Nociceptive threshold was assessed by Hot Plate test at baseline, immediately and 24h after the first session, immediately and 24h after the last session. Variance analysis of repeated measurements followed by Bonferroni was performed for intra-group comparison. Results: Physical restraint and 30 seconds stimulation (sham-tDCS) increased pain sensitivity (P≤0.05), and tDCS treatment was able to prevent the thermal hyperalgesia. Our original tDCS montage is similar to that used in the procedure with humans, because it is not an invasive technique. The electrodes are positioned on the head, and the animals are immobilized during the 20-minute treatment. As this procedure could involve behavior and neurochemical alterations due to stress induced by restriction (thus, it creates a research bias), we hypothesized that a 30-second electrical stimulus application (sham-tDCS) and the physical restriction used during tDCS treatment might alter nociceptive response in rats. Conclusion: There are methodological limitations in the present tDCS-technique. Although active-tDCS treatment is able to prevent these harmful effects, interference of these factors has to be considered during the results' analysis. Future adaptations of the tDCS-technique in rats are required to evaluate its therapeutic effects (AU)

Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology.

The central sensitization syndrome (CSS) encompasses disorders with overlapping symptoms in a structural pathology spectrum ranging from persistent nociception [e.g., osteoarthritis (OA)] to an absence of tissue injuries such as the one presented in fibromyalgia (FM) and myofascial pain syndrome (MPS). First, we hypothesized that these syndromes present differences in their cortical excitability parameters assessed by transcranial magnetic stimulation (TMS), namely motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and short intracortical facilitation (SICF). Second, considering that the presence of tissue injury could be detected by serum neurotrophins, we hypothesized that the spectrum of structural pathology (i.e., from persistent nociception like in OA, to the absence of tissue injury like in FM and MPS), could be detected by differential efficiency of their descending pain inhibitory system, as assessed by the conditioned pain modulation (CPM) paradigm. Third, we explored whether brain-derived neurotrophic factor (BDNF) had an influence on the relationship between motor cortex excitability and structural pathology. This cross-sectional study pooled baseline data from three randomized clinical trials. We included females (n = 114), aged 19-65 years old with disability by chronic pain syndromes (CPS): FM (n = 19), MPS (n = 54), OA (n = 27) and healthy subjects (n = 14). We assessed the serum BDNF, the motor cortex excitability by parameters the TMS measures and the change on numerical pain scale [NPS (0-10)] during CPM-task. The adjusted mean (SD) on the SICI observed in the absence of tissue injury was 56.36% lower than with persistent nociceptive input [0.31(0.18) vs. 0.55 (0.32)], respectively. The BDNF was inversely correlated with the SICI and with the change on NPS (0-10)during CPM-task. These findings suggest greater disinhibition in the motor cortex and the descending pain inhibitory system in FM and MPS than in OA and healthy subjects. Likewise, the inter-hemispheric disinhibition as well as the dysfunction in the descending pain modulatory system is higher in chronic pain without tissue injury compared to a structural lesion. In addition, they suggest that a greater level of serum BDNF may be involved in the processes that mediate the disinhibition of motor cortex excitability, as well as the function of descending inhibitory pain modulation system, independently of the physiopathology mechanism of musculoskeletal pain syndromes.

Obesity and Hyperlipidemia Modulate Alveolar Bone Loss in Wistar Rats.

BACKGROUND: A positive association between obesity-associated metabolic disorders (e.g., hyperlipidemia and diabetes) and periodontitis has been demonstrated in the literature. This study evaluates the role of cafeteria diet-induced obesity/hyperlipidemia (CAF) on alveolar bone loss (ABL) in rats. METHODS: Sixty male Wistar rats were randomly divided in four groups: control, periodontitis (PERIO), obesity/hyperlipidemia (CAF), and obesity/hyperlipidemia plus periodontitis (CAF+PERIO). Groups CAF and CAF+PERIO were exposed to a high-fat, hypercaloric diet. At week 12, periodontal disease was induced in groups PERIO and CAF+PERIO by ligatures in the upper second molar. The contralateral tooth was considered the intragroup control. Body weight and Lee index were evaluated weekly during the experiment. Serum glucose and cholesterol/triglycerides in the liver were evaluated, and percentage of ABL was measured by microcomputed tomography. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were evaluated by enzyme-linked immunosorbent assay at week 17. RESULTS: Body weight, Lee index, and cholesterol/triglycerides in the liver increased in groups exposed to the cafeteria diet. Groups PERIO and CAF+PERIO exhibited a significantly higher ABL compared to control and CAF groups. The presence of obesity and hyperlipidemia significantly increased ABL in the CAF+PERIO group compared to the PERIO group (53.60 ± 3.44 versus 42.78 ± 7.27, respectively) in the sides with ligature. Groups exposed to CAF exhibited higher ABL in the sides without ligature. No differences were observed among groups for IL-1ß and TNF-α. CONCLUSION: Obesity and hyperlipidemia modulate the host response to challenges in the periodontium, increasing the expression of periodontal breakdown.

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<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 (AU)

Factors associated to salivary flow alterations in dry mouth female patients / Fatores associados a alterações no fluxo salivar em pacientes com xerostomia

BACKGROUND AND OBJECTIVES: Saliva plays an important role in oral health; it is involved in lubrication of the oral mucosa, protection against infections, transport of nutrients and digestive enzymes, remineralization of teeth, as well as aiding in chewing, swallowing and speech. Reductions in the amount of saliva are known to increase the risk of oral diseases. This study investigated the factors associated to salivary flow alterations and its relationship with age, burning mouth syndrome, psychiatric and sleep disorders, systemic diseases and chronic drug use. METHODS: A total of 30 patients complaining of dry mouth without unbalanced systemic diseases were included. Questionnaires regarding socio-demographic data, xerostomia, burning mouth, depression and anxiety symptoms, and sleep disturbances were applied. Measures of salivary flow rates were obtained using spit method. Correlation of hyposalivation and quantitative data was determined using a multivariate regression model. RESULTS: The age range was 31-83 years, hyposalivation was correlated positively with sleep disorder (β=0.079, 95% CI, to 0,124) and negatively with burning mouth (β=-0.043, 95% CI, -0.083 to -0.002). CONCLUSION: These results provide evidences regarding the association between reduced salivary flow and burning mouth, sleep disorders and chronic use of psychotropic medicines, and we highlighted the important role of antidepressants on modulation of burning mouth sensation...

JUSTIFICATIVA E OBJETIVOS: A saliva tem um papel importante na saúde bucal; está envolvida na lubrificação da mucosa oral, na proteção contra infecções, no transporte de nutrientes e enzimas digestivas, na remineralização dentária e também auxilia na mastigação, deglutição e fala. Sabe-se que reduções na quantidade de saliva aumentam o risco de doenças bucais. Este estudo investigou os fatores associados a alterações no fluxo salivar e seu relacionamento com idade, síndrome de ardência bucal, distúrbios psiquiátricos e do sono, doenças sistêmicas e uso crônico de medicamentos. MÉTODOS: Foi incluído um total de 30 pacientes com queixa de xerostomia sem doenças sistêmicas desequilibradas. Foram aplicados questionários sobre dados sociodemográficos, xerostomia, ardência bucal, sintomas de depressão e ansiedade e distúrbios do sono. As medidas de fluxo salivar foram obtidas pelo método spit. A correlação entre hipo-salivação e dados quantitativos foi determinada por um modelo univariado de regressão. RESULTADOS: A idade various de 31;83 anos, hipo-salivação foi correlacionada positivamente com distúrbios do sono (β=0,079, 95% CI, 0,033 a 0,124) e negativamente com ardência bucal (β=-0,043, 95% CI, -0,083 a -0,002). CONCLUSÃO: Esses resultados trazem evidências sobre a associação entre fluxo salivar reduzido e ardência bucal, distúrbios do sono e uso crônico de psicotrópicos, e destacamos o importante papel dos antidepressivos na modulação da sensação de ardência bucal...

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs / Efeitos da administração aguda e crônica de metilprednisolona no estresse oxidativo em pulmões de ratos

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. .

Objetivo: Determinar os efeitos da administração aguda e crônica de metilprednisolona no estresse oxidativo, por meio da quantificação da peroxidação lipídica (POL) e do potencial antioxidante reativo total (PART), em pulmões de ratos. Métodos: Quarenta ratos Wistar foram divididos em quatro grupos: tratamento agudo, com ratos recebendo uma dose única de metilprednisolona (50 mg/kg i.p.); controle agudo, com ratos recebendo injeção unida de salina; tratamento crônico, com ratos recebendo metilprednisolona v.o. na água do bebedouro (6 mg/kg por dia durante 30 dias; e controle crônico, com ratos recebendo água de bebedouro normal). Resultados: Os níveis de PART foram significativamente maiores no grupo tratamento agudo que no grupo controle agudo, sugerindo uma melhora do sistema de defesa pulmonar. Os níveis de POL foram significativamente maiores no grupo tratamento crônico que no grupo controle crônico, indicando dano oxidativo no tecido pulmonar. Conclusões: Nossos resultados sugerem que o uso agudo de corticoides foi benéfico aos tecidos pulmonares, enquanto seu uso crônico não o foi. O uso crônico de metilprednisolona parece aumentar os níveis pulmonares da POL. .

Effects of melatonin and estradiol on chronic pain during post menopause

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 variations within the menstrual cycle and an increase in pain 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 partially 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 be the cause of 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.

Prevalência de morbidades e sintomas em idosos: um estudo comparativo entre zonas rural e urbana / The prevalence of morbidity and symptoms among the elderly: a comparative study between rural and urban areas

Realizou-se um estudo transversal, com a população idosa moradora nas zonas rural e urbana caracterizando a prevalência de morbidades e sintomas. Entrevistou-se 229 idosos, com média de idade de 72,3 anos, 57,2% residem na zona urbana, 56,3% são do sexo feminino. As morbidades mais relatadas por residentes da zona urbana foram: insônia (37,7%), ansiedade (32,1%), depressão (26,7%); e na rural, diabetes (13,3%). Nesta, a Doença de Alzheimer foi mais prevalente em idosos que utilizam agrotóxicos (21,7%). Os sintomas mais prevalentes por moradores da zona urbana foram: tosse/coriza e visão alterada (41,2%), alergia/coceira (11,4%). Na rural, boca seca (25,4%), visão alterada (35,6%) e dor nas pernas (66,1%) que também foram mais prevalentes em quem utilizava agrotóxicos. O uso de Equipamentos de Proteção Individual de forma incompleta foi de 85,4% e 45,1% descartam as embalagens de forma inadequada. Há a necessidade de desenvolvimento de programas de saúde pública que auxiliem na promoção de saúde do idoso, e que considere a possível exposição dessa população a agrotóxicos com um determinante em saúde.

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, Alzheimer´s 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.

Análise de prescrições médicas dispensadas em farmácia no Sistema Único de Saúde / Analysis of medical prescriptions dispensed in pharmacy in the Brazilian Unified Health System

Objetivo: Analisar os indicadores propostos pela Organização Mundial de Saúde(OMS) em prescrições médicas fornecidas a pacientes atendidos em Centro de Saúde do município de Lajeado – RS.Métodos: Foi realizado estudo transversal, que avaliou dados relativos ao padrãode prescrição em Sistema Único de Saúde (SUS).Resultados: Foram analisadas 292 prescrições médicas. Destas, 282 continham o nome do paciente, mas em apenas três havia o seu endereço. Em 243 prescrições, constava o nome do médico, e, em 227, havia o número de inscrição no Conselho de Medicina. Foram identificados 713 medicamentos, com média de2,44 por prescrição, sendo aqueles com ação em sistema cardiovascular os mais prevalentes. Observou-se, ainda, que 611 medicamentos constavam da Relação Nacional de Medicamentos Essenciais (RENAME), 509 constavam da Relação Municipal de Medicamentos Essenciais (REMUME) e 489 constavam da Lista Modelo da OMS.Conclusão: A maioria dos indicadores de prescrição avaliados apresentou adequação ao que é proposto pela OMS. No entanto, ainda há dificuldades, como aquelas referentes a itens faltantes nas prescrições médicas, o que pode interferir no uso racional de medicamentos.

Aim: To analyze the indicators proposed by the World Health Organization (WHO) inmedical prescriptions provided to patients seen in a Health Center of the municipalityof Lajeado, RS, Brazil.Methods: This was a cross-sectional study evaluating data on prescriptions of patients seen in the Brazilian Unified Health System.Results: We analyzed 292 medical prescriptions. Of these, 282 had the patient name, but only three had the address; the doctor’s name was present in 243 prescriptions; the registration number on the Board of Medicine of the prescriber was identified in 227. We identified 713 drugs, with a mean of 2.44 medicines per prescription, being the most prevalent those acting in the cardiovascular system.We also observed that 611 drugs were included in the National List of Essential Medicines (RENAME), 509 were included in the Municipal Essential Medicines List(REMUME), and 489 were included in the Model List of WHO.Conclusion: Most prescribing indicators evaluated showed adequacy regarding the propositions of WHO. However, there are still difficulties, such as those observed with missed items in the medical prescriptions, which may interfere in the rational use of medicines.

Interrelação entre síndrome metabólica, estresse crônico e ritmos circadianos de marcadores adipogênicos: uma revisão / Interrelation between metabolic syndrome, chronic stress and circadian rhythms of adipogenic markers: a review

Alterações de ritmos circadianos são relacionadas ao desenvolvimento de transtornos metabólicos como obesidade e síndrome metabólica. Além disto, a disponibilidade e o consumo de alimentos altamente palatáveis ricos em gordura e a exposição a situações estressantes podem contribuir na incidência e na severidade destas doenças crônicas, provocando modificações no balanço energético, alterações no metabolismo de lipídeos e adipogênese. Nesta revisão, abordaremos os aspectos cronobiológicos que podem ser influenciados pela exposição a estresse crônico e a obesidade, além dos mecanismos que contribuem para o crescimento de doenças metabólicas (AU)

Alterations in circadian rhythms are associated with the development of metabolic disorders, such as obesity and metabolic syndrome. Moreover, the availability and consumption of highly palatable foods rich in fat and the exposure to stressful situations may contribute to the incidence and severity of these chronic diseases, leading to changes in energy balance, alterations in lipid metabolism and adipogenesis. This review aimed to discuss the chronobiological aspects that can be influenced by the response to chronic stress and obesity, as well as the mechanisms that contribute to the development of metabolic diseases (AU)

Rational use of medicines: prescribing indicators at different levels of health care

This multicenter study aimed to investigate prescribing patterns of drugs at different levels of health care delivery in university-affiliated outpatient clinics located in eight cities in the South and Midwest of Brazil. All prescriptions collected were analyzed for various items, including WHO prescribing indicators. A total of 2,411 prescriptions were analyzed, and 469 drugs were identified. The number of drugs prescribed per encounter, the frequency of polypharmacy, and the percentage of encounters with at least one injection or antibiotic prescribed were higher in centers providing primary health care services, compared to those where this type of care is not provided. Most drugs (86.1%) were prescribed by generic name. In centers with primary health care services, drug availability was higher, drugs included in the National and Municipal Lists of Essential Medicines were more frequently prescribed, and patients were given more instructions. However, warnings and non-pharmacological measures were less frequently recommended. This study reveals trends in drug prescribing at different levels of health care delivery in university-affiliated outpatient clinics and indicates possible areas for improvement in prescribing practices.

Este estudo multicêntrico teve como objetivo investigar o padrão de prescrição de medicamentos para pacientes ambulatoriais atendidos em serviços de saúde vinculados a universidades com diferentes níveis de atenção, em oito cidades do sul e centro-oeste do Brasil. As prescrições coletadas foram submetidas à análise de diversos itens, incluindo os indicadores de prescrição propostos pela OMS. No total, 2.411 prescrições foram analisadas e 469 medicamentos foram identificados. O número de medicamentos prescritos por consulta, a frequência de polifarmácia e a porcentagem de consultas com pelo menos um medicamento injetável ou um antimicrobiano prescrito foram maiores em centros de saúde que ofereciam cuidados de atenção básica, em comparação com aqueles que não dispunham desse tipo de atendimento. A maioria dos medicamentos foi prescrita pelo nome genérico (86,1%). Em unidades com cuidados de atenção básica, a acessibilidade foi maior, a prescrição de medicamentos presentes nas Listas Nacional e Municipais de Medicamentos Essenciais foi mais frequente e instruções foram fornecidas aos pacientes mais comumente. Entretanto, advertências e medidas não farmacológicas foram indicadas com menor frequência. Este estudo revela tendências de prescrição de medicamentos em serviços de saúde ligados a universidades, com diferentes níveis de atenção, e indica possíveis áreas de melhoria na prática da prescrição.