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.

Validation of the Brazilian version of the child pain catastrophizing scale and its relationship with a marker of central sensitization

Abstract Objectives The Pain Catastrophizing Scale-Child version (PCS-C) allows to identify children who are prone to catastrophic thinking. We aimed to adapt the Brazilian version of PCS-C (BPCS-C) to examine scale psychometric properties and factorial structure in children with and without chronic pain. Also, we assessed its correlation with salivary levels of Brain-Derived Neurotrophic factor (BDNF). Methods The Brazilian version of PCS-C was modified to adjust it for 7-12 years old children. To assess psychometric properties, 100 children (44 with chronic pain from a tertiary hospital and 56 healthy children from a public school) answered the BPCS-C, the visual analogue pain scale, and questions about pain interference in daily activities. We also collected a salivary sample to measure BDNF. Results We observed good internal consistency (Cronbach's value = 0.81). Parallel analysis retained 2 factors. Confirmatory factor analysis of our 2-factor model revealed consistent goodness-of-fit (IFI = 0.946) when compared to other models. There was no correlation between visual analogue pain scale and the total BPCS-C score; however, there was an association between pain catastrophizing and difficulty in doing physical activities in school (p= 0.01). BPCS-C total scores were not different between groups. We found a marginal association with BPCS-C (r= 0.27, p= 0.01) and salivary BDNF levels. Discussion BPCS-C is a valid instrument with consistent psychometric properties. The revised 2-dimension proposed can be used for this population. Children catastrophism is well correlated with physical limitation, but the absence of BPCS-C score differences between groups highlights the necessity of a better understanding about catastrophic thinking in children.

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

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

Dysfunctional eating behavior in fibromyalgia and its association with serum biomarkers of brain plasticity (BDNF and S100B): an exploratory study

ABSTRACT Objectives: To assess disordered eating, hunger and satiety perceptions in women with fibromyalgia (FM) compared to healthy controls (HC) and their association with biomarkers of brain plasticity (brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B)). Subjects and methods: Cross-sectional exploratory study. The sample included FM (n = 20) and HC (n = 19), matched to age and waist perimeter. Dysfunctional eating was assessed through the Three Factor Eating Questionnaire and Eating Disorders Examination with a questionnaire. Hunger and satiety levels were rated by a Numerical Scale. Serum leptin, S100B and BDNF were analyzed. Results: The MANCOVA analysis showed that the mean of Emotional Eating rates was 30.65% higher in FM compared to HC ( p = 0.015). Eating, shape and weight concerns were 77.77%, 57.14% and 52.22% higher in FM ( p = <0.001) compared to HC, respectively. Moreover, the FM group reported higher scores for feeling of hunger "[5.2 (±2.9) vs. 4.8 (±2.0); p = 0.042] and lower scores for satiety [7.0 (±1.7) vs . 8.3 (±1.0); p = 0.038]. In the FM group, serum BDNF was negatively associated with hunger (r = - 0.52; p = 0.02), while S100B was positively associated with hunger scores (r = 0.463; p = 0.004). Conclusion: The present findings support the hypothesis that the association between FM and obesity can be mediated by a hedonistic pathway. Further research is needed.

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.

The profile of dexamethasone combined with transcranial direct current stimulation in rats submitted to an arthritis model / O perfil da dexametasona combinada com estimulação transcraniana por corrente contínua em ratos submetidos a um modelo de artrite

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund's adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: Para investigar métodos mais seguros e eficazes para o manejo da artrite reumatoide, avaliou-se o efeito do tratamento com dexametasona (DEX, 0,25mg/kg) combinado com estimulação transcraniana por corrente contínua (ETCC) sobre parâmetros comportamentais e bioquímicos de ratos submetidos a um modelo de artrite reumatoide. MÉTODOS: Trinta e seis ratos Wistar foram alocados em 4 grupos: controle+DEX (CTRL+DEX), artrite+DEX (AR+DEX), artrite+DEX+sham-ETCC (AR+DEX+sham-ETCC) e artrite+DEX+ETCC (AR+DEX+ETCC). O modelo de artrite foi induzido pela administração de complete Freund's adjuvant (CFA) na pata. Edema na pata e a alodínia mecânica foram avaliadas por pletismômetro e teste de von Frey, respectivamente. 14 dias após injeção de CFA, ratos foram tratados por 8 dias (DEX e/ou ETCC). Atividade locomotora foi avaliada pelo teste do campo aberto. TNF-alfa (hipocampo e medula espinal) e BDNF (córtex e tronco) foram mensurados por ELISA. RESULTADOS: Nas medições pré-tratamento, ratos com artrite exibiram aumento de o inchaço articular e alodínia mecânica comparados ao grupo controle, confirmando o estabelecimento de modelo de dor crônica. Também se observou discreto efeito antinociceptivo da dexametasona combinada com ETCC no modelo de artrite. O modelo de dor induziu um aumento no comportamento de grooming e reduziu os níveis de TNF-alfa no hipocampo; estes efeitos foram revertidos nos grupos sham- e ETCC ativo. Entretanto, não foram observados efeitos da DEX ou ETCC nos níveis de BDNF no córtex cerebral ou no tronco encefálico. CONCLUSÃO: Apesar dos discretos efeitos observados, não se pode descartar a ETCC como uma abordagem terapêutica não farmacológica para o manejo da dor crônica inflamatória na artrite reumatoide.

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)

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)

Desempenho acadêmico de doutores egressos do Programa de Pós-Graduação em Medicina: Ciências Médicas da Faculdade de Medicina da UFRGS / Academic performance of doctoral graduates from the Graduate Program in Medicine: Medical Sciences at UFRGS School of Medicine

Introdução: embora, no Brasil, muito tenha sido feito para estimular a criação e manutenção de programas de pós-graduação ainda há carência de meios para avaliar e para mensurar a evolução profissional dos egressos. O objetivo é compreender a trajetória dos Doutores formados pelo Programa de Pós-Graduação em Medicina Ciências Médicas (PPGCM), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS) e propor um índice de desempenho acadêmico e de inserção profissional. Métodos: foi realizado um estudo transversal. Foram coletados dados dos Currículos Lattes dos egressos de doutorado do Programa de Pós-Graduação em Medicina: Ciências Médicas (PPGCM), no período de 1987 a 2014. Foram extraídos apenas os dados pertinentes a sua origem, curso de graduação e de mestrado, produção intelectual, inserção acadêmica e a posição profissional. Resultados: foram analisados 324 doutores egressos, 221 eram graduados em Medicina. Foram utilizadas as variáveis: graduação em medicina, vínculo laboral em universidade pública, exerce atividade como orientador em nível de doutorado, exerce atividade como orientador em nível de mestrado, bolsista de produtividade em pesquisa do CNPq e possui registro do índice H no currículo Lattes. O coeficiente de determinação (R2) demonstrou que as variáveis incluídas no modelo explicam 99% do modelo hierárquico. Conclusão: os resultados demonstram que os egressos têm contribuído para a construção de conhecimento qualificado disseminado em jornais de circulação internacional, formação de recursos humanos, interagir e criar parcerias em seu ambiente de trabalho, gerenciar e repassar o conhecimento, bem como para fomentar o conhecimento na área das ciências médicas com relevância regional, nacional e internacional. (AU)

Introduction: Although, in Brazil, much has been done to encourage the creation and maintenance of graduate programs, there remains a lack of means to assess and measure the professional outcomes of graduates. The objective is to understand the trajectory of doctoral graduates from the Graduate Program in Medicine: Medical Sciences (PPGCM), School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), and propose an index for academic performance and professional placement. Methods: A cross-sectional study was conducted. Data available at CV Lattes database of the National Council for Scientific and Technological Development (CNPq) were collected on doctoral graduates from the PPGCM, from 1987 to 2014. Only data pertaining to their origin, undergraduate and master's degrees, intellectual output, academic performance, and professional placement were retrieved. Results: Data on 324 doctoral graduates were analyzed, 221 had graduated in medicine. Undergraduate degree, employment at a public university, working as a doctoral-level advisor, working as a master's-level advisor, CNPq research productivity grantee, and having a recorded h-index in the Lattes curriculum were collected. The coefficient of determination (R 2 ) demonstrated that the variables included in the model explain 99% of the hierarchical model. Conclusion: The results show that the graduates have contributed to developing qualified knowledge disseminated in international newspapers, training human resources, interacting and creating partnerships in the workplace, managing and passing on knowledge, as well as fostering knowledge in the area of medical sciences with regional, national, and international relevance. (AU)

Predictors of in-hospital mortality in patients undergoing elective surgery in a university hospital: a prospective cohort / Preditores de mortalidade intra-hospitalar em pacientes submetidos a cirurgias não eletivas em um hospital universitário: uma coorte prospectiva

Abstract Introduction Morbidity and mortality associated with urgent or emergency surgeries are high compared to elective procedures. Perioperative risk scores identify the non-elective character as an independent factor of complications and death. The present study aims to characterize the population undergoing non-elective surgeries at the Hospital de Clínicas de Porto Alegre and identify the clinical and surgical factors associated with death within 30 days postoperatively. Methodology A prospective cohort study of 187 patients undergoing elective surgeries between April and May 2014 at the Hospital de Clínicas, Porto Alegre. Patient-related data, pre-operative risk situations, and surgical information were evaluated. Death in 30 days was the primary outcome measured. Results The mean age of the sample was 48.5 years, and 84.4% of the subjects had comorbidities. The primary endpoint was observed in 14.4% of the cases, with exploratory laparotomy being the procedure with the highest mortality (47.7%). After multivariate logistic regression, age (odds ratio [OR] 1.0360, p < 0.05), anemia (OR 3.961, p < 0.05), acute or chronic renal insufficiency (OR 6.075, p < 0.05), sepsis (OR 7.027, p < 0.05), and patient-related risk factors for mortality, in addition to the large surgery category (OR 7.502, p < 0.05) were identified. Conclusion The high mortality rate found may reflect the high complexity of the institution's patients. Knowing the profile of the patients assisted helps in the definition of management priorities, suggesting the need to create specific care lines for groups identified as high risk in order to reduce perioperative complications and deaths.

Resumo Introdução Quando comparada a procedimentos eletivos, a morbimortalidade associada às cirurgias de urgência ou emergência é alta. Escores de risco perioperatório identificam o caráter não eletivo como fator independente de complicações e morte. O presente estudo objetiva caracterizar a população submetida a cirurgias não eletivas no Hospital de Clínicas de Porto Alegre e identificar fatores clínicos e cirúrgicos associados à morte em 30 dias no pós-operatório. Metodologia Coorte prospectiva de 187 pacientes submetidos a cirurgias não eletivas entre abril e maio de 2014 no Hospital de Clínicas de Porto Alegre. Avaliaram-se dados relacionados ao paciente, situações de risco pré-operatórias e informações do âmbito cirúrgico. Mensurou-se óbito em 30 dias como desfecho primário. Resultados A média de idade da amostra foi 48,5 anos; 84,4% dos indivíduos apresentavam comorbidades. O desfecho primário foi observado em 14,4% dos casos, laparotomia exploradora foi o procedimento com maior mortalidade (47,7%). Após regressão logística multivariada, identificaram-se idade (odds ratio [OR] 1.0360, p < 0,05), anemia (OR 3.961, p < 0,05), insuficiência renal aguda ou crônica agudizada (OR 6.075, p < 0,05) e sepse (OR 7.027, p < 0,05) como os fatores de risco relacionados ao paciente significativos para mortalidade, além da categoria cirurgia de grande porte (OR 7.502, p < 0,05). Conclusão A elevada taxa de mortalidade encontrada pode refletir a alta complexidade dos pacientes da instituição. O conhecimento do perfil dos pacientes atendidos auxilia na definição de prioridades de gerenciamento, sugere a necessidade de criação de linhas de cuidado específicas para grupos identificados como de alto risco, a fim de reduzir complicações e óbitos no perioperatório.

Distinct aspects of pain catastrophizing according to chronic pain syndromes

Introduction: Catastrophizing is the tendency to magnify the threat value of pain and has been associated with measures of physical and psychological disability among individuals with several pain conditions. The aim of this study was to investigate whether pain catastrophizing is differentially associated with distinct pain syndromes. Methods: This is a cross-sectional study including 158 patients (40 with fibromyalgia, 25 with myofascial pain syndrome, 33 with chronic tensional type headache, 33 with endometriosis, and 27 with knee osteoarthritis) and 93 healthy subjects. The recruitment procedure occurred in concurrence with randomized controlled trials. Participants answered the following instruments: Brazilian Portuguese Pain-Catastrophizing Scale, Beck Depression Inventory II, State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, visual analogue scale for pain, as well as a sociodemographic questionnaire. Results: For the total pain catastrophizing score, patients with endometriosis had significantly more catastrophizing thoughts than knee osteoarthritis (p < 0.05). Healthy participants had lower scores than any clinical group. More interestingly were the dimensions of pain catastrophizing, which showed significant differences in more than two groups, especially magnification scores, since these scores were able to discriminate, in a particular way, the majority of clinical samples from each other. We also observed differences between rumination, magnification and helplessness scores in all groups, suggesting that the characteristics of pain catastrophizing are distinct according to the pain disorder. Conclusions: The results suggest that dimensions of pain catastrophizing differ between pain syndromes. Therefore, it is important that researchers and clinicians focus on cognitive and emotional aspects of pain perception to have more successful interventions.

Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire - Current Short (QUIP-CS) - Translation and validation of content of Portuguese Version / Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire - Current Short (QUIP-CS) - Tradução e validação de conteúdo em português do Questionário para Avaliação de Distúrbios Impulsivo-Compulsivos na Doença de Parkinson

ABSTRACT Objective Parkinson's disease (PD) management is usually successfully reached with proper pharmacological treatment. However, PD patients can manifest neuropsychiatric symptoms secondary to medical therapy, including impulse control disorders (ICD), presenting as pathological gambling, hypersexuality, compulsive buying, drinking or eating disorders. We translated and validated the Portuguese version of the gold-standard questionnaire Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire, or (QUIP) for identifying ICDs in PD patients. Methods Translation, back translation and submission to instrument developer was performed, that approved its new version comparing it to his original, validated version, with no loss of it's original properties. Then, the Portuguese version was administered to 30 PD patients. They also were asked to rate from 1 to 5 the level of comprehensibility of the questions. Results The average level of comprehension was 4.06 ± 0.69 DP, considering 3 or more as acceptable. No patient has answered 1 or 2. Conclusion Our results on Portuguese version of QUIP-CS show that QUIP-CS translated and corrected version was easily understood and easily self-applied.

RESUMO Objetivo O manejo da doença de Parkinson (DP) é usualmente alcançado com sucesso com o tratamento farmacológico apropriado. Entretanto, os pacientes com DP podem manifestar sintomas neuropsiquiátricos secundários à terapêutica, como a síndrome de descontrole dos impulsos (SDI), que se apresenta como o jogar patológico, a hipersexualidade, o comprar, beber ou comer compulsivos. Traduzimos e validamos a versão em português do questionário padrão-ouro para identificação de transtornos impulsivo-compulsivos na DP (QUIP-CS) para identificar nesses pacientes a presença de SDI. Métodos Foram realizadas a tradução, a retrotradução e a submissão do instrumento ao desenvolvedor deste, que aprovou a nova versão comparando esta à sua, que já está validada, sem a perda das suas propriedades originais. Após, a versão em português foi administrada a 30 pacientes com o diagnóstico de DP. Eles também foram solicitados a classificar o nível de compreensibilidade das questões, graduando-as de 1 a 5. Resultados O nível médio de compreensão foi 4,06 ± 0,69 DP, considerando-se 3 ou mais como aceitável. Nenhum paciente respondeu 1 ou 2. Conclusão Os nossos resultados para a versão em português da QUIP-CS mostraram que essa versão, traduzida e corrigida, foi facilmente compreendida e aplicada pelos próprios pacientes.

Cafeteria diet increases liquid intake and serum creatinine levels in rats

Introduction: Important changes in human dietary pattern occurred in recent decades. Increased intake of processed foods leads to obesity, which is related with the development of chronic diseases such as type 2 diabetes mellitus, hypertension, as well as cardiovascular and chronic kidney diseases. The prevalence of hypertension has also dramatically increased in recent years, and high sodium intake contributes to this scenario. In healthy individuals, kidneys are the primary end-organs that regulate sodium homeostasis. This study aims to evaluate renal function parameters and systolic blood pressure measurements in an animal model of obesity. Methods: Sixty-day-old male Wistar rats (n=30) were divided into two groups: standard (SD) and cafeteria diet (CD). Cafeteria diet was altered daily and was composed by crackers, wafers, sausages, chips, condensed milk, and soda. All animals had free access to water and chow and the experiment was carried out for 6 weeks. Weight gain, sodium and liquid intake control, systolic blood pressure measurements, and renal function parameters were evaluated. Results: Animals exposed to cafeteria diet had an increase of 18% in weight compared to the control group. Sodium intake was increased by cafeteria diet and time (F(1,28)=773.666, P=0.001 and F(5,28)=2.859, P=0.02, respectively) and by the interaction of both factors (F(6,28)=2.859, P=0.02). On liquid intake occurred only effect of cafeteria diet and time (F(1,28)=147.04, P=0.001 and F(5,28)=3.996, P=0.003, respectively). Cafeteria diet exposure also induced an increase on creatinine serum levels (P=0.002), however this effect was not observed on creatinine urine levels (P>0.05) nor on systolic pressure measurements (Students' t test, P>0.05). Conclusions: Obesity induced by cafeteria diet exposure increases liquid intake and alters creatinine serum levels, an important renal function marker. Considering the high consumption of hypercaloric food currently in the world, further studies are required to elucidate the modifications on renal function triggered by this diet over time (AU)

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)

Perfil de resiliência em pacientes com dor crônica / Perfil de resiliencia en pacientes con dolor crónico / Resilience profile of patients with chronic pain

Resumo: O objetivo deste estudo foi identificar perfis de resiliência em paciente com dor crônica. Utilizando a Análise de Classes Latentes, em uma amostra de 414 pacientes com dor crônica musculoesquelética, foram identificados três perfis: resiliência primária (40%), composto por indivíduos de até 40 anos, que têm alta escolaridade, buscam os cuidados médicos, não trabalham e não apresentam sintomas de estresse psicológico; resiliência secundária (30%), composto por mulheres com mais de 54 anos, que têm baixo nível de escolaridade, buscam cuidados médicos, não trabalham e apresentam baixa probabilidade de experimentar sintomas de estresse psicológico; resiliência terciária (29%), composto por mulheres com médio nível de escolaridade, idade entre 40 e 54 anos, que trabalham, não buscam cuidados médicos e têm alta probabilidade de experimentar sintomas de estresse psicológico. Os três perfis revelam caminhos distintos de resiliência na dor crônica com relevância para prática clínica, destacando a atuação multidisciplinar nos cuidados ao paciente com dor crônica.

Resumen: El objetivo de este estudio fue identificar perfiles de resiliencia en pacientes con dolor crónico. Utilizando el análisis de clases latentes, en una muestra de 414 pacientes con dolor crónico musculoesquelético, fueron identificados tres perfiles: resiliencia primaria (40%), compuesto por individuos de hasta 40 años, que tienen una alta escolaridad, buscan cuidados médicos, no trabajan y no presentan síntomas de estrés psicológico; resiliencia secundaria (30%), compuesto por mujeres con más de 54 años, que tienen bajo nivel de escolaridad, buscan cuidados médicos, no trabajan y presentan baja probabilidad de experimentar síntomas de estrés psicológico; resiliencia terciaria (29%), compuesto por mujeres con medio nivel de escolaridad, edad entre 40 y 54 años, que trabajan, no buscan cuidados médicos y tienen una alta probabilidad de experimentar síntomas de estrés psicológico. Los tres perfiles revelan caminos distintos de resiliencia en el dolor crónico, con relevancia para la práctica clínica, destacando la actuación multidisciplinaria en los cuidados al paciente con dolor crónico.

Abstract: The aim of this study was to identify resilience profiles of patients with chronic pain. Using latent class analysis in a sample of 414 patients with chronic musculoskeletal pain, three profiles were identified: primary resilience (40%), consisting of individuals 40 years or younger with high education, who seek medical care, are not working, and without symptoms of psychological stress; secondary resilience (30%), consisting of women over 54 years of age with low schooling, who seek medical care, are not working, and with low likelihood of symptoms of psychological stress; tertiary resilience (29%), women with medium schooling, 40 to 54 years old, working, who do not seek medical care, and with a high likelihood of symptoms of psychological stress. The three profiles display different paths of resilience in chronic pain that are relevant to clinical practice, highlighting the importance of multidisciplinary care for patients with chronic pain.

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)

Promising treatments for neuropathic pain / Tratamentos promissores para dor neuropática

In the last few years the understanding of mechanisms and, consequently, the diagnosis of neuropathic pain (NP) has becoming progressively clearer in clinical practice. However, the treatment of such condition remains challenging so far. One of the reasons for such difficulty is the diversity of mechanisms involved in NP generation and its persistency. In the present review we discuss several treatment modalities for NP that are scantily applied in daily clinical practice. For that, we collected positive clinical evidence of unusual and SECS (Safe, Easy, Cheap, and Sensible) approaches for NP. The aim of this review is not to establish the “state of the art” or rigid guidelines for NP treatment. In a different way, we only want bring new possibilities of treatment to the readers and also to motivate investigators to confirm those positive preliminary but promising results for NP reliev.

Nos últimos anos, a compreensão dos mecanismos e consequentemente do diagnóstico da dor neuropática (DN) têm se tornado cada vez mais claros na prática clínica. Entretanto, o tratamento desta condição continua sendo um desafio. Uma das razões para tal dificuldade é diversidade de mecanismos envolvidos na geração e perpetuação da DN. Na presente revisão, os autores discutem várias modalidades de tratamento para DN pouco utilizadas na prática clínica diária. Para isso, selecionamos evidências clínicas positivas de abordagens para DN consideradas não-convencionais e do tipo “SFBR” (Seguro, Fácil, Barato e Racional). O objetivo desta revisão não é estabelecer o “estado da arte” ou diretrizes rígidas para o tratamento da DN. Diferente disso, pretendemos apenas trazer aos leitores novas possibilidades de tratamento assim como motivar pesquisadores a confirmar estes resultados preliminares, mas promissores para o alívio da DN.

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...

One-time Exposure to General Anesthetics Alters Nociceptive Response and Nucleotide Hydrolysis in Infant Rats.

Aims: The objective was to evaluate the single exposure of general anesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30. Place of Study: All experiments were performed at the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The Institutional Committee approved the experimental protocol f (GPPG-HCPA protocol No: 08149). Methodology: Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): the 1st ED – control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR) and the 2nd ED – control (C), fentanyl/S(+)-ketamine (FK) and fentanyl/S(+)- ketamine/surgery (FK-SUR). Nociceptive responses were evaluated using the formalin and tail-flick tests, and the ectonucleotidase activities were evaluated by spinal cord synaptosome. All assessments were performed at P14 and P30. Results: The FK and FK-SUR groups displayed an increased latency at P30. For the ectonucleotidase activity analysis, the following results were observed: (a) in the 1st ED, the ISO group displayed a reduction in ATPase and ADPase, and both ISO and ISOSUR displayed a reduction in AMPase activity at P14; (b) in the 2nd ED, the FK group displayed an increase in AMPase activity at P14 and increased ATPase activity at P30, and both FK and FK-SUR exhibited an increase in AMPase activity at P30. Conclusion: Our results indicate that single administration of general anesthetics at P14 is able to promote changes in the nociceptive response in the intermediate-term, and in the ectonucleotidase activities in the short- and medium-terms.