Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial.

INTRODUCTION: Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. OBJECTIVE: The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. METHODS: This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. RESULTS: At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p = 0.001), and placebo+tDCS Sham (p = 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p = 0.001), effect of pain on activities (p = 0.014) and emotions (p = 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). CONCLUSION: Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.

Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial

Abstract Introduction Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. Objective The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. Methods This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. Results At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p= 0.001), and placebo+tDCS Sham (p= 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p= 0.001), effect of pain on activities (p= 0.014) and emotions (p= 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). Conclusion Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.

Nociceptive Profile and Analgesic use of Patients Submitted to Rotator Cuff Repair Surgery: A Prospective Cohort.

Objective This study aimed to evaluate the nociceptive profile and the intake of analgesic drugs of patients submitted to rotator cuff repair surgery. Also, to evaluate the nociceptive thresholds and the integrity of the descending inhibitory system, pain catastrophism and prevalence of nociceptive or neuropathic pain. Methods Approved by the Ethics Committee of La Salle University (1.325.433/2015). 40 patients (>18 years old) who underwent rotator cuff repair surgery (divided in small and large injuries) were recruited. The used instruments were: Sociodemographic Questionnaire, Functional Pain Scale, Visual Analogue Scale (VAS), Quantitative Sensory Test (QST) and Conditioned Pain Modulation Task (CPM). Results Patients had a significant difference in pain thresholds QST heat (independent samples t test) and quality of sleep, mood and anxiety (paired t test) in groups preoperative. There was a significant correlation between preoperative CPM and postoperative VAS (Pearson Correlation). It was observed that, in preoperative, 38 patients used analgesics continuously. Besides that, in postoperative, use of opioid drugs was higher in patients with small injury (13 patients) than in those with large injury (9 patients). Conclusion Therefore, patients with rotator cuff injuries did not present alterations in the descending inhibitory system, but showed alterations in pain thresholds, which may interfere in the postoperative period and still be related to the consumption of analgesics.

Nociceptive Profile and Analgesic use of Patients Submitted to Rotator Cuff Repair Surgery: A Prospective Cohort / Perfil nociceptivo e uso de analgésicos em pacientes submetidos à cirurgia de reparo do manguito rotador: Coorte prospectiva

Abstract Objective This study aimed to evaluate the nociceptive profile and the intake of analgesic drugs of patients submitted to rotator cuff repair surgery. Also, to evaluate the nociceptive thresholds and the integrity of the descending inhibitory system, pain catastrophism and prevalence of nociceptive or neuropathic pain. Methods Approved by the Ethics Committee of La Salle University (1.325.433/2015). 40 patients (>18 years old) who underwent rotator cuff repair surgery (divided in small and large injuries) were recruited. The used instruments were: Sociodemographic Questionnaire, Functional Pain Scale, Visual Analogue Scale (VAS), Quantitative Sensory Test (QST) and Conditioned Pain Modulation Task (CPM). Results Patients had a significant difference in pain thresholds QST heat (independent samples t test) and quality of sleep, mood and anxiety (paired t test) in groups preoperative. There was a significant correlation between preoperative CPM and postoperative VAS (Pearson Correlation). It was observed that, in preoperative, 38 patients used analgesics continuously. Besides that, in postoperative, use of opioid drugs was higher in patients with small injury (13 patients) than in those with large injury (9 patients). Conclusion Therefore, patients with rotator cuff injuries did not present alterations in the descending inhibitory system, but showed alterations in pain thresholds, which may interfere in the postoperative period and still be related to the consumption of analgesics.

Resumo Objetivo O objetivo deste estudo foi avaliar o perfil nociceptivo e o uso de analgésicos em pacientes submetidos à cirurgia de reparo do manguito rotador. Além disso, os limiares nociceptivos e a integridade do sistema inibidor descendente, o catastrofismo da dor e a prevalência de dor nociceptiva ou neuropática também foram analisados. Métodos Este estudo foi aprovado pelo Comitê de Ética da Universidade La Salle (1.325.433/2015). Quarenta pacientes (maiores de 18 anos) submetidos à cirurgia de reparo do manguito rotador (divididos entre aqueles com lesões pequenas e grandes) participaram do estudo. Os instrumentos utilizados foram o Questionário Sociodemográfico, a Escala Funcional de Dor, a Escala Visual Análoga (EVA), o Teste Sensorial Quantitativo (QST) e a Tarefa de Modulação Condicionada da Dor (CPM). Resultados Os pacientes apresentaram diferenças significativas nos limiares de dor e QST de calor (teste t de amostras independentes) e qualidade do sono, humor e ansiedade (teste t pareado) nos grupos pré-operatórios. Houve uma correlação significativa entre CPM pré-operatória e EVA pós-operatória (correlação de Pearson). Observou-se que, no período pré-operatório, 38 pacientes utilizavam analgésico de forma contínua. Além disso, no período pós-operatório, o uso de opioides foi maior nos pacientes com lesões pequenas (13 pacientes) em comparação àqueles com lesões grandes (nove pacientes). Conclusão Os pacientes com lesão do manguito rotador não apresentaram alterações no sistema inibidor descendente, mas sim alterações nos limiares de dor, o que pode interferir no período pós-operatório e estar relacionado ao consumo de analgésicos.

Fibromyalgia: A Review of Related Polymorphisms and Clinical Relevance.

Fibromyalgia (FM) is a chronic pain syndrome that affects the central nervous system and generates disability, which is characterized by generalized pain, fatigue, and functional decline. In this review, we aimed to identify the polymorphisms related to the pathophysiology of FM and the clinical characteristics generated by genetic influence. Only original studies with genes related to FM were considered, totaling 27 articles. The genes found were: MTHFR, RGS4, MYT1L, TACR1, SCN9A, DRD3, ADRB2, IL-4, HLA-DRB1, EDN1, CNR1, TAAR1, OPRM1, ADRA1A, ADRB3, BDNF, GRIA4, HTR3A, HTR3B, HTR2A, SERPINA 1 or A1AT, NRXN3, GCH1, MEFV, TRPV3, SLC6A4, ACE I/D, TSPO, COMT, and MAOA. Several genes related to different pain syndromes and altered pain thresholds have been identified and some polymorphisms were related to susceptibility to FM. It was observed that 73.33% of the genes related to FM were also associated with some psychological disorders, such as anxiety, depression, schizophrenia, and obsessive and compulsive disorder, and 40.00% with pain sensitivity and/or migraine, besides other disorders associated (drug addiction, autoimmune disorders, circulatory problems, and metabolic alterations). This review demonstrated an association of FM and genetic polymorphisms that can expand our knowledge about the pathophysiology of this disease.

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.

Pain catastrophizing in daughters of women with fibromyalgia: a case-control study.

Fibromyalgia is a syndrome characterized by chronic pain related to the musculoskeletal system. Patients feel incapable and show catastrophic thoughts (exaggeration of the sensations) related to painful events. This study aimed to compare catastrophic thoughts of pain between daughters of women with fibromyalgia and daughters of women without fibromyalgia, no daughter having the syndrome. It was a case-control study in which 76 women were included: 38 daughters of women diagnosed with fibromyalgia (case group), and 38 daughters of women without fibromyalgia (control group). The Brazilian versions of the Profile of Chronic Pain: Screen, the Pittsburgh Sleep Quality Index, the Pain Catastrophizing Scale, Resilience Scale, Beck Depression Inventory-II, and the State-Trait Anxiety Inventory were used. Data were tabulated and analyzed using SPSS 20.0. Continuous variables were compared between the groups using the Mann-Whitney U test or Student's t-test for independent samples. A significant difference was considered at p < 0.05. Regarding catastrophism, the case group had higher total catastrophism compared to the control group (p = 0.025). Daughters of patients with fibromyalgia showed higher rumination and magnification levels related to pain (p = 0.028 and p = 0.007, respectively) but did not show hopelessness. This study concludes that daughters of women with fibromyalgia are more likely to have symptoms of fibromyalgia due to their visualization of the syndrome. This indicates that emotional aspects may induce changes, and additional research on an individual basis is necessary.

Aplicação de bundle de prevenção de pneumonia em UTI pediátrica / Application of a pneumonia prevention bundle in a pediatric ICU

Objetivo: avaliar o impacto de um bundle de prevenção da Pneumonia Associada à Ventilação Mecânica em uma Unidade de Terapia Intensiva pediátrica. Método: trata-se de um estudo quantitativo e quase-experimental realizado em uma Unidade de Terapia Intensiva pediátrica. Analisaram-se todos os Pacientes em Ventilação Mecânica durante um período de dois anos (nas fases pré e pós-intervenção), em relação à ocorrência de Pneumonia Associada à Ventilação Mecânica. Verificaram-se, a partir do bundle adotado, os seguintes itens: cabeceira elevada; prevenção de úlcera gástrica; higiene oral e avaliação diária da sedação. Resultados: demonstra-se que houve uma diminuição da incidência de pneumonias (P=0,002) e no tempo médio de uso do ventilador após a aplicação do protocolo (P=0,045). Detectou-se uma diferença significativa no que diz respeito às bactérias, com predomínio das Gram-negativas no grupo dos pacientes sem o uso do protocolo, em comparação ao grupo com o bundle (P=0,001). Conclusão: concluiu-se que os fatores de risco para a PAV são considerados modificáveis e que podem ser prevenidos por meio da criação de protocolos específicos de cuidados. Defende-se que a implementação do bundle na Pediatria pode reduzir as infecções nosocomiais, destacando-se a pneumonia relatada neste estudo.(AU)

Objective: to evaluate the impact of a prevention bundle for Mechanical Ventilation Associated Pneumonia in a Pediatric Intensive Care Unit. Method: This is a quantitative and quasiexperimental study conducted in a pediatric Intensive Care Unit. All Patients in Mechanical Ventilation were analyzed during a period of two years (in the pre- and post-intervention phases), in relation to the occurrence of Mechanical Ventilation Associated Pneumonia. The following items were verified from the adopted bundle: high head; prevention of gastric ulcer; oral hygiene and daily assessment of sedation. Results: it is shown that there was a decrease in the incidence of pneumonia (P=0.002) and in the mean time of use of the ventilator after the application of the protocol (P=0.045). A significant difference was detected regarding bacteria, with predominance of Gram-negative in the group of patients without the use of the protocol, compared to the group with the bundle (P=0.001). Conclusion: It was concluded that the risk factors for VAP are considered modifiable and can be prevented through the creation of specific care protocols. It is argued that the implementation of bundle in pediatrics can reduce nosocomial infections, highlighting the pneumonia reported in this study.(AU)

Objetivo: evaluar el impacto de un bundle para la prevención de la neumonía asociada a la ventilación mecánica en una unidad de cuidados intensivos pediátricos. Método: se trata de un estudio cuantitativo y cuasiexperimental realizado en una Unidad de Cuidados Intensivos pediátricos. Todos los pacientes con ventilación mecánica fueron analizados durante un período de dos años (en las fases previa y posterior a la intervención), en relación con la aparición de neumonía asociada a la ventilación mecánica. Desde el bundle adoptado, se verificaron los siguientes elementos: cabecero elevado; prevención de úlcera gástrica; la higiene bucal y la evaluación de la sedación diaria. Resultados: se demostró que hubo una disminución en la incidencia de neumonía (P = 0,002) y en el tiempo medio de uso del ventilador posterior a la aplicación del protocolo (P = 0,045). Se detectó una diferencia significativa con respecto a las bacterias, con predominio de gramnegativos en el grupo de pacientes sin uso del protocolo, frente al grupo con el bundle (p = 0,001). Conclusión: se concluyó que los factores de riesgo de NAV se consideran modificables y que se pueden prevenir mediante la creación de protocolos de atención específicos. Se argumenta que la implementación del bundle en Pediatría puede reducir las infecciones nosocomiales, destacando la neumonía reportada en este estudio.(AU)

Neuroinflammatory effects of tDCS in ovariectomized rats with chronic inflammation

Introduction: Postmenopausal women are more susceptible to chronic conditions, such as osteoporosis, arthritis, and other inflammatory diseases. We investigated the effects of transcranial direct current stimulation (tDCS) on biomarker levels in ovariectomized rats subjected to an inflammatory model. Methods: Twenty adult female Wistar rats underwent ovariectomy and complete Freund's adjuvant (CFA)-induced inflammation. We divided them into 2 groups: OAS (sham tDCS) and OAT (active tDCS). Fifteen days later, the rats underwent bimodal tDCS treatment (20 min, 0.5 mA, 8 days). After 24 h of the last tDCS session, we killed the rats and collected tissue samples (hypothalamus, cerebral cortex, and brainstem) for biomarker analysis by ELISA. We removed the paws for histological analysis. Results: Active tDCS increased hypothalamic and cortical TNF-α and NGF levels, hypothalamic and brainstem IL-1ß levels, and hypothalamic IL-10 levels. Histology of paws showed an inflammatory profile. We observed a small tDCS effect, not statistically significant. Discussion: Bimodal tDCS had an effect on the central inflammatory axis, with a small effect on the peripheral site as evaluated by histology in the current study. (AU)

Sobrecarga do cuidador de pacientes oncológicos em cuidados paliativos / Overburden on the caregivers of oncological patients in palliative care

Objetivo: correlacionar o impacto da sobrecarga do cuidador na qualidade de vida do paciente oncológico em cuidados paliativos Método: trata-se de um estudo quantitativo, descritivo, observacional, transversal, com 50 pacientes oncológicos em cuidados paliativos e 50 cuidadores. Aplicou-se um questionário sociodemográfico para os cuidadores e familiares, a Escala Zarit Burden Interview, o Questionário EORT QLQ ­C15-PAL, a Escala de Resiliência Adaptada de Wagnild & Young e a Escala de Pensamento Catastrófico da Dor, uso do Teste t, Correlação de Spearman, Correlação de Pearson e regressão linear. Utilizou-se o Programa SPSS, versão 20.0 para a análise dos dados. Resultados: informa-se que os domínios da qualidade de vida que mostraram associação independente com a sobrecarga do cuidador foram a fatiga, a falta de apetite, a constipação e o impacto global. Manteve-se associação independente pelo catastrofismo da dor do paciente com a sobrecarga do cuidador, não houve associação entre a resiliência do paciente e a sobrecarga do cuidador e 40% dos cuidadores apresentaram sobrecarga severa. Conclusão: nota-se que o aumento da sobrecarga do cuidador diminui a qualidade de vida do paciente oncológico em cuidados paliativos.(AU)

Objective: to correlate the impact of caregiver burden on the quality of life of cancer patients in palliative care. Method: this is a quantitative, descriptive, observational, cross-sectional study with 50 cancer patients in palliative care and 50 caregivers. A sociodemographic questionnaire was applied for caregivers and family members, the Zarit Burden Interview Scale, the EORT QLQ ­C15-PAL Questionnaire, the Wagnild & Young Adapted Resilience Scale and the Catastrophic Pain Thinking Scale, using the t Test, Spearman's correlation, Pearson's correlation and linear regression. The SPSS program, version 20.0, was used for data analysis. Results: it is reported that the domains of quality of life that showed an independent association with caregiver burden were fatigue, lack of appetite, constipation and the global impact. An independent association was maintained due to the catastrophism of the patient's pain with the burden of the caregiver, there was no association between the patient's resilience and the burden of the caregiver and 40% of the caregivers presented severe burden. Conclusion: it is noted that the increase in caregiver burden reduces the quality of life of cancer patients in palliative care. (AU)

Objetivo: correlacionar el impacto de la carga del cuidador en la calidad de vida de los pacientes oncológicos en cuidados paliativos Método: este es un estudio cuantitativo, descriptivo, observacional, transversal con 50 pacientes oncológicos en cuidados paliativos y 50 cuidadores. Se aplicó un cuestionario sociodemográfico para cuidadores y miembros de la familia, la Escala Zarit Burden Interview, el Cuestionario EORT QLQ-C15-PAL, la Escala de Resiliencia Adaptada Wagnild& Young y la Escala de Pensamiento de Dolor Catastrófico, usando la Prueba t, Correlación de Spearman, la Correlación de Pearson y regresión lineal. El programa SPSS, versión 20.0, se utilizó para el análisis de datos. Resultados: se informa que los dominios de calidad de vida que mostraron una asociación independiente con la carga del cuidador fueron fatiga, falta de apetito, estreñimiento y el impacto global. Se mantuvo una asociación independiente debido al catastrofismo del dolor del paciente con la sobrecarga del cuidador, no hubo asociación entre la resistencia del paciente y la sobrecarga del cuidador y el 40% de los cuidadores presentaron una sobrecarga severa. Conclusión: se observa que el aumento de la sobrecarga del cuidador reduce la calidad de vida de los pacientes oncológicos en cuidados paliativos.(AU)

Sleep alterations in patients with the human immunodeficiency virus and chronic pain / Alterações do sono em pacientes vivendo com o vírus da imunodeficiência humana e dor crônica

ABSTRACT BACKGROUND AND OBJECTIVES: In patients with chronic pain, insomnia is reported between 50 and 88% of them. It is essential to recognize sleep disorders to estimate its repercussions on the quality of life and to seek knowledge that supports the necessary interventions. This study aims to identify the possible factors that influence sleep quality, as well as its prevalence in these patients. METHODS: Sample consisting of 68 patients (58 women, 10 men), the mean age of 45.3±10.3 years, with a positive diagnosis of human immunodeficiency virus undergoing antiretroviral and chronic pain treatment in Porto Alegre, RS. The Pittsburgh Sleep Quality Index was used to assess the components of the scale as well as their overall score. For the classification of the type of chronic pain, the Leeds Assessment of Neuropathic Symptoms and Signs scale was used, which differentiates nociceptive and neuropathic pain. RESULTS: Patients classified with no pain, nociceptive pain and neuropathic pain. Overall score divided into good sleep, bad sleep and sleep disorder, where patients without pain accounted for 8.8%, 16.2 and 2.9% respectively. With nociceptive pain 4.4, 11.8 and 5.9%, respectively. With neuropathic pain 4.4, 23.5 and 22.1% respectively. Patients with neuropathic pain had the highest rates of poor sleep and sleep disorder, accounting for 50.0% and using more sleeping pills compared to the control group (p<0.05). CONCLUSION: There is a high prevalence of sleep disorders or poor sleep in patients with the human immunodeficiency virus with neuropathic pain. The importance of assessing the sleep as an essential part of the clinical assessment should be recognized and incorporated without delay by health professionals.

RESUMO JUSTIFICATIVA E OBJETIVOS: Em pacientes com dor crônica, a insônia é relatada entre 50 e 88% deles. É fundamental reconhecer as alterações do sono para estimar suas repercussões na qualidade de vida e buscar conhecimentos que respaldem as necessárias intervenções. Este estudo buscou identificar os possíveis fatores que influenciam a qualidade do sono, bem como suas prevalências nesses pacientes. MÉTODOS: Amostra constituída por 68 pacientes (58 mulheres e 10 homens) com idade média de 45,3±10,3 anos, diagnóstico positivo para o vírus da imunodeficiência humana em tratamento antirretroviral e dor crônica, de uma instituição em Porto Alegre, RS. O Questionário do Índice de Qualidade de Sono de Pittsburgh foi usado para a avaliação dos componentes da escala de sono, bem como sua pontuação total. Para a classificação do tipo de dor crônica foi utilizada a escala Leeds Assessment of Neuropathic Symptoms and Signs, que diferencia dor nociceptiva e neuropática. RESULTADOS: Os pacientes foram classificados em sem dor, dor nociceptiva e dor neuropática. A pontuação global foi dividida em sono bom, sono ruim e distúrbio do sono, onde os pacientes sem dor representaram 8,8, 16,2 e 2,9% respectivamente. Com dor nociceptiva 4,4, 11,8 e 5,9% respectivamente. Com dor neuropática 4,4, 23,5 e 22,1% respectivamente. Os pacientes com dor neuropática apresentaram os maiores índices de sono ruim e distúrbio do sono, representando 50,0% e utilizavam mais fármacos para dormir em comparação com o grupo controle (p<0,05). CONCLUSÃO: Existe elevada prevalência de distúrbios do sono ou sono ruim em pacientes portadores do vírus com dor neuropática. A importância da avaliação do sono como parte essencial da avaliação clínica deve ser reconhecida e incorporada sem demora pelos profissionais de saúde.

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.

Higher Cortical Facilitation and Serum BDNF Are Associated with Increased Sensitivity to Heat Pain and Reduced Endogenous Pain Inhibition in Healthy Males.

Background: Although the brain-derived neurotrophic factor (BDNF) has been intensively investigated in animal models of chronic pain, its role in human pain processing is less understood. Objective: To study the neurophysiology of BDNF modulation on acute experimental pain, we performed a cross-sectional study. Methods: We recruited 20 healthy male volunteers (19-40 years old) and assessed their serum BDNF levels, quantitative sensory testing, and cortical excitability parameters using transcranial magnetic stimulation. Results: Linear regression models demonstrated that the BDNF (ß = -5.245, P = 0.034) and intracortical facilitation (ß = -3.311, P = 0.034) were inversely correlated with heat pain threshold (adjusted R2 = 44.26). The BDNF (ß = -3.719, P ≤ 0.001) was also inversely correlated with conditioned pain modulation (adjusted R2 = 56.8). Conclusions: Our findings indicate that higher serum BDNF and intracortical facilitation of the primary motor cortex are associated with increased sensitivity to heat pain and high serum BDNF with reduced pain inhibition during noxious heterotopic stimulation.

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.

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)

Dor neuropática em pacientes com HIV/AIDS em uso de terapia antirretroviral / Neuropathic pain in HIV/AIDS patients using antiretroviral therapy

A infecção pelo vírus da imunodeficiência humana (HIV) representa um dos maiores problemas de saúde da atualidade em virtude de seu caráter pandêmico e gravidade. O uso da terapia antirretroviral está associado ao desenvolvimento de diferentes tipos de dor, sendo a dor neuropática uma delas. A dor neuropática ocorre pela lesão do sistema nociceptivo, que envolve mudanças moleculares, fisiológicas e anatômicas. Considerando que a infecção por HIV gera custos elevados para o sistema de saúde, e que suas comorbidades elevam ainda mais esses custos, a compreensão dos mecanismos da dor nessa população possibilita uma melhor assistência e uma redução da carga para o sistema. A dor neuropática pode apresentar diferentes possíveis mecanismos fisiopatológicos envolvidos, tornando-se um desafio para o tratamento de pacientes com HIV. A compreensão sobre a neurofisiologia da dor neuropática e o HIV pode promover melhores abordagens aos pacientes e a redução de comorbidades associadas, com impacto na qualidade de vida (AU)

Human immunodeficiency virus (HIV) infection is a major health problem nowadays due to its pandemic character and severity. The use of antiretroviral therapy is associated with the development of different types of pain, and neuropathic pain is one of them. Neuropathic pain is caused by an injury to the nociceptive system, which involves molecular, physiological and anatomical changes. Considering that HIV infection generates high costs for the health system, and that its comorbidities raise such costs even more, understanding the mechanisms of pain in this population can result in better care practices and reduction of burden to the system. Neuropathic pain may present different pathophysiological mechanisms becoming a challenge for HIV treatment. The understanding of the neurophysiology of neuropathic pain and the HIV can promote better patient approaches and the reduction of associated comorbidities with an impact on quality of life (AU)

Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology.

BACKGROUND AND OBJECTIVES: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility. METHODS: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37). RESULTS: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%). CONCLUSION: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

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 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.

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.