Brain-Derived Neurotrophic Factor Modulates the Effect of Sex on the Descending Pain Modulatory System in Healthy Volunteers.

OBJECTIVES: We investigated sex differences and the influence of brain-derived neurotrophic factor (BDNF) in the descending pain modulatory system (DPMS), as measured by change on the numerical pain scale (NPS; 0-10) during conditioned pain modulation (CPM task; primary outcome) and by function of the corticospinal motor pathway and heat pain thresholds (HPTs; secondary outcomes). METHODS: This cross-sectional study included healthy volunteers ranging in age from 18 to 45 years (32 male and 24 female). Assessment included serum BDNF, HPT, change on the NPS (0-10) during the CPM task, and motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). RESULTS: The MEP (Mv) amplitude was larger in male participants compared with female participants (mean [SE] = 1.55 [0.34] vs mean [SE] = 1.27 [0.27], respectively, P = 0.001). The mean NPS (0-10) during CPM task changed more substantially for female compared with male participants (mean [SE] = -3.25 [2.01] vs mean [SE] = -2.29 [1.34], respectively, P = 0.040). In addition, a higher serum BDNF (adjusted index for age) was associated with a larger decrease of the NPS during CPM task (P = 0.003), although further regression analyses by sex showed that this was only significant for females (P = 0.010). CONCLUSIONS: Significant sex differences were identified in DPMS function and corticospinal motor pathway integrity. Nevertheless, BDNF was associated with the function of the DPMS in female but not male participants, indicating that sex and neuroplasticity state are crucial factors for pain perception in healthy subjects.

The brief measure of preoperative emotional stress screens preoperative maladaptive psychological features and predicts postoperative opioid use: an observational study.

BACKGROUND: The Brief Measure of Preoperative Emotional Stress (B-MEPS) is a suitable screening tool for Preoperative Emotional Stress (PES). However, personalized decision-making demands practical interpretation of the refined version of B-MEPS. Thus, we propose and validate cut-off points on the B-MEPS to classify PES. Also, we assessed if the cut-off points screened preoperative maladaptive psychological features and predicted postoperative opioid use. METHODS: This observational study comprises samples of two other primary studies, with 1009 and 233 individuals, respectively. The latent class analysis derived emotional stress subgroups using B-MEPS items. We compared membership with the B-MEPS score through the Youden index. Concurrent criterion validity of the cut-off points was performed with the severity of preoperative depressive symptoms, pain catastrophizing, central sensitization, and sleep quality. Predictive criterion validity was performed with opioid use after surgery. RESULTS: We chose a model with three classes labeled mild, moderate, and severe. The Youden index points -0.1663 and 0.7614 of the B-MEPS score classify individuals, in the severe class, with a sensitivity of 85.7% (80.1%-90.3%) and specificity of 93.5% (91.5-95.1%). The cut-off points of the B-MEPS score have satisfactory concurrent and predictive criterion validity. CONCLUSIONS: These findings showed that the preoperative emotional stress index on the B-MEPS offers suitable sensitivity and specificity for discriminating the severity of preoperative psychological stress. They provide a simple tool to identify patients prone to severe PES related to maladaptive psychological features, which might influence the perception of pain and analgesic opioid use in the postoperative period.

Pain catastrophizing is associated with the Val66Met polymorphism of the brain-derived neurotrophic factor in fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient's daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM. METHODS: In a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory - STAI), depression (Beck Depression Inventory II - BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire - FIQ; Central Sensitization Inventory validated and adapted for Brazilian population - CSI-BP; Pittsburgh Sleep Quality Index - PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism. RESULTS: Val allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups. CONCLUSIONS: The findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.

The brief measure of preoperative emotional stress screens preoperative maladaptive psychological features and predicts postoperative opioid use: an observational study

Abstract Background: The Brief Measure of Preoperative Emotional Stress (B-MEPS) is a suitable screening tool for Preoperative Emotional Stress (PES). However, personalized decision-making demands practical interpretation of the refined version of B-MEPS. Thus, we propose and validate cut-off points on the B-MEPS to classify PES. Also, we assessed if the cut-off points screened preoperative maladaptive psychological features and predicted postoperative opioid use. Methods: This observational study comprises samples of two other primary studies, with 1009 and 233 individuals, respectively. The latent class analysis derived emotional stress subgroups using B-MEPS items. We compared membership with the B-MEPS score through the Youden index. Concurrent criterion validity of the cut-off points was performed with the severity of preoperative depressive symptoms, pain catastrophizing, central sensitization, and sleep quality. Predictive criterion validity was performed with opioid use after surgery. Results: We chose a model with three classes labeled mild, moderate, and severe. The Youden index points −0.1663 and 0.7614 of the B-MEPS score classify individuals, in the severe class, with a sensitivity of 85.7% (80.1%-90.3%) and specificity of 93.5% (91.5-95.1%). The cut-off points of the B-MEPS score have satisfactory concurrent and predictive criterion validity. Conclusions: These findings showed that the preoperative emotional stress index on the B-MEPS offers suitable sensitivity and specificity for discriminating the severity of preoperative psychological stress. They provide a simple tool to identify patients prone to severe PES related to maladaptive psychological features, which might influence the perception of pain and analgesic opioid use in the postoperative period.

The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0-10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin's effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0-10) during the CPM-task in the placebo group was -1.91 [-1.81 (1.67) vs. -0.1 (1.61)], and in the melatonin group was -3.5 [-0.94 (1.61) vs. -2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin's effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. -20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. -0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = -8.27[(2.89 (11.18) vs. -11.16 (9.75); 95% CI = -15.38 to -1.16)]. However, melatonin's effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03205033.

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.

Pain catastrophizing is associated with the Val66Met polymorphism of the brain-derived neurotrophic factor in fibromyalgia

Abstract Background: Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient's daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM. Methods: In a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory - STAI), depression (Beck Depression Inventory II -BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire - FIQ; Central Sensitization Inventory validated and adapted for Brazilian population - CSI-BP; Pittsburgh Sleep Quality Index - PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism. Results: Val allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups. Conclusions: The findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.(AU)

Sociodemographic and obstetric factors related to low birth weight in the context of early pregnancy / Fatores sociodemográficos e obstétricos relacionados ao baixo peso em recém-nascidos no contexto da gravidez precoce

Abstract Objectives: to analyze sociodemographic and obstetric factors that may influence the occurrence of low birth weight in the context of early pregnancy. Methods: the sample consisted of 232 pregnant teenagers, aged 10-19 years old, were assisted at a public maternity hospital in Aracaju-SE during the period of August 2012 to July 2016. The data collection was conducted through a structured questionnaire. Results: low birth weight was observed in 41.38% of the newborns and there was a statistical association between the educational level and the marital status with the occurrence of low birth weight in newborns among teenage mothers, with p=0.0286 and p=0.0247, respectively. Conclusions: the socioeconomic factors may contribute to the occurrence of low birth weight in newborns of teenage mothers and teenage pregnancy at this age represents a serious public health problem.

Resumo Objetivos: analisar os fatores sociodemográficos e obstétricos que podem influenciar na ocorrência do baixo peso ao nascer no contexto da gravidez precoce. Métodos: amostra constou de 232 adolescentes grávidas, na faixa etária de 10 a 19 anos, atendidas em uma maternidade pública de Aracaju-SE, Brasil, durante o período de agosto de 2012 a julho de 2016. A coleta de dados foi realizada através de um questionário estruturado. Resultados: observou-se baixo peso em 41,38% dos recém-nascidos e que o nível de escolaridade e o tipo de vínculo com o parceiro tiveram relevância estatística para a ocorrência do baixo peso em recém-nascidos de mães adolescentes, com p=0,0286 e p=0,0247, respectivamente. Conclusões: os fatores socioeconômicos podem contribuir para a ocorrência de baixo peso em recém-nascidos de mães adolescentese que a gravidez nesta faixa etária constitui grave problema de saúde pública de natureza multifatorial.

Morphine treatment alters nucleotidase activities in rat blood serum.

Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 µg per day alters NTPDase and 5'-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5'-diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5'-triphosphate hydrolysis activity was lower at P16, and adenosine 5'-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period.

A vulnerabilidade ao HIV em adolescentes: estudo retrospectivo em um centro de testagem e aconselhamento / Vulnerability to HIV in adolescents: a retrospective study at a counseling and testing center

O presente estudo objetivou identificar o perfil de vulnerabilidade e a sua relação com a escolaridade de adolescentes com sorologia positiva para o vírus da imunodeficiência humana (HIV) de um Centro de Testagem e Aconselhamento (CTA). O delineamento caracterizou-se como transversal retrospectivo. A amostra foi de 100 indivíduos de ambos os sexos, entre 13 e 19 anos de idade, com sorologia positiva para HIV, no período de 2002 a 2010, em um CTA da região Sul do Brasil. A média de idade foi de 17,7 anos, com sexo feminino perfazendo 65% da amostra e com prevalência em escolaridade (oito a 11 anos de estudo). Não houve diferença significativa entre as variáveis categóricas que compõem vulnerabilidade e sexo. O perfil de vulnerabilidade evidenciado foi feminização, associação de baixa escolaridade com “motivo de não usar preservativo com parceiro fixo”, “uso de drogas no último ano”, “doença sexualmente transmissível no último ano” e relação sexual como “tipo de exposição”. Salienta-se a necessidade de desenvolvimento de intervenções educativas para a prevenção do HIV/AIDS em adolescentes.

El presente estudio tuvo como objetivo identificar la relación entre el perfil de vulnerabilidad para el virus de la inmunodeficiencia humana (VIH) y el nivel de instrucción de adolescentes seropositivos de un Centro de Consejería y Pruebas (CTA). El diseño se caracteriza por ser transversal retrospectivo. La muestra consistió en 100 individuos de ambos sexos, entre 13 y 19 años de edad, con serología VIH positiva, en el período 2002-2010, a un CTA del sur de Brasil. La edad promedio fue de 17,7 años, con las mujeres que componen el 65% de la muestra y su prevalencia en la educación (8-11 años de escolaridad). No hay diferencias significativas entre las variables categóricas que componen vulnerabilidad y sexo. El perfil de vulnerabilidad evidenció la feminización, la asociación entre bajo nivel educativo y "razón para no usar preservativos con una pareja estable", "consumo de drogas en el último año "," enfermedad de transmisión sexual en el último año"y la relación sexual como "una especie de la exposición". Hacemos hincapié en la necesidad de llevar a cabo medidas educativas para la prevención del VIH / SIDA en adolescentes.

The present study aimed to identify the vulnerability profile of HIV-positive adolescents at a Counseling and Testing Center (CTA) and its relationship with the individuals' level of education. It is a retrospective cross-sectional study carried out from 2002 to 2010 at a CTA in Southern Brazil. Sample consisted of 100 HIV-positive subjects of both sexes, aged between 13 and 19 years. The average age was 17.7 years; female subjects made up 65 % of the sample and had the highest educational attainment (8 to 11 years of schooling). There were no significant differences between the categorical variables that comprise vulnerability and sex. Vulnerability profile highlighted feminization, an association between low level of education and the following variables: "reason not to use condoms with a stable partner"; "drug use in the last year"; "sexually transmitted diseases in the last year"; and sexual intercourse as a " type of exposure". The researchers emphasize the need to implement educational programs for the prevention of HIV/AIDS in adolescents.

Oficinas educativas sobre HIV/Aids: uma proposta de intervencao para idosos / Educative workshops on HIV/Aids: proposing interventions for elderly

O objetivo do estudo foi avaliar a eficácia de uma oficina educativa sobre HIV/aids em um grupo de idosos. A população incluiu 471 indivíduos entre 60 e 91 anos composta principalmente por mulheres (83,1%). Procedeu-se a aplicação e reaplicação de um questionário organizado em cinco domínios, antes e após as oficinas. O teste de McNemar foi utilizado para comparar as respostas pré e pós-oficina (p<0,05) no programa estatístico STATA 12. Dentre os domínios, a maior variação (202,72%) ocorreu no domínio "conceito" sobre a fase assintomática da infecção. No domínio "transmissão", a variação foi de 168,53% para a transmissão do HIV por picada de mosquito. No domínio "prevenção", na questão sobre existência do preservativo feminino, a variação foi de 44%. O domínio "vulnerabilidade" indicou 34,93% na questão da aids relacionada a grupos específicos. No domínio "tratamento", a abordagem da cura para a aids obteve 50,85% de variação. A realização das oficinas demonstrou ser uma intervenção eficaz nos domínios "conceito", "transmissão", "prevenção", "vulnerabilidade" e "tratamento" nos idosos participantes da pesquisa.

This study aimed to evaluate the effectiveness of educational workshops instructing about HIV/Aids in a group of elderly. The population included 471 individuals between 60 and 91 years old, mostly women (83.1%). A questionnaire comprising five domains was answered by participants before and after taking the educational workshops. McNemar test was used to assess differences between pre-and post-workshop, through thr software STATA 12 (p<0.05). The greatest variation (202.72%) was observed in the "concept" domain related to the asymptomatic infection phase. Regarding "HIV transmission", the variation was 168.53%. The domain "prevention" had variation of 44% concerning the existence of female condom. The "vulnerability" domain inquired about Aids association in specific groups, and a difference of 34.93% was observed. In the "treatment" domain, when inquiring about Aids cure, 50.85% variation was observed. The educational workshops were effective for the domains "concept", "transmission", "prevention", "vulnerability" and "treatment" in a group of elderly.