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.

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)

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.

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.

Avaliação do impacto da exposição a agrotóxicos sobre a saúde de população rural: Vale do Taquari (RS, Brasil) / Evaluation of the impact of exposure to pesticides on the health of the rural population: Vale do Taquari, State of Rio Grande do Sul (Brazil)

Este estudo transversal teve o objetivo de avaliar possível associação entre contato com agrotóxicos e prevalência de doenças crônicas em população rural do Sul do Brasil. Três municípios foram aleatoriamente escolhidos. A amostra selecionada por conveniência foi recrutada durante três meses (2005) e se compôs de 298 sujeitos de ambos os sexos, com idade entre 18 e 65 anos e que procuravam farmácia pública ou privada para a compra de medicamentos. Os dados obtidos, mediante entrevistas estruturadas, demonstraram que 68,4 por cento dos entrevistados exerciam atividade rural, dos quais 74,8 por cento eram membros de famílias de agricultores e tinham contato com agrotóxicos. A média de idade foi 51±16,5 anos para os entrevistados com contato com agrotóxicos e 50±17,9 anos para os sem contato. A amostra foi constituída de 36,2 por cento por homens e 57,7 por cento dos indivíduos que apresentavam mais de quatro anos de estudo. O contato direto ou indireto com agrotóxicos associou-se ao relato de várias doenças, sendo as neurológicas e as orais as mais prevalentes. Houve associação com relato de condições dolorosas, de modo que indivíduos com contato com agrotóxicos apresentaram em torno de duas vezes mais chances de as referirem. Os dados corroboram os da literatura e indicam a necessidade de promoção de medidas de proteção e prevenção da saúde da população rural.

The scope of this cross-sectional study was to assess a possible link between contact with pesticides and the prevalence of chronic disease in the rural population in the south of Brazil. Three municipalities were randomly chosen. The sample selected was recruited over three months (2005) and was composed of 298 subjects of both sexes, between 18 and 65 years of age, who frequented public or private pharmacies for the purchase of medication. Data obtained by means of structured interviews revealed that 68.4 percent of those interviewed worked in rural activities, and 74.8 percent of these were members of families working in agriculture with contact with pesticides. The average age was 51+16.5 years of age for the interviewees with contact with pesticides and 50+17.9 years for those without contact. The sample was composed of 36.2 percent of men, and 57.7 percent of the individuals had more than four years of education. Direct or indirect contact with pesticides was associated with the report of several diseases, with neurological and oral diseases being the most prevalent. There was a link with painful conditions and individuals with contact with pesticides reported twice as many diseases. The data corroborate the literature and draw attention to the need for promoting measures to protect the health of the rural population.

Avaliação de fatores associados ao diagnóstico de queimação bucal: um estudo preliminar / Evaluation of factors associated to diagnosis of burning mouth: a preliminary study

Objetivo: avaliar fatores associados ao diagnóstico de ardência bucal como xerostomia, hipossalivação, sintomas depressivos, ansiedade, transtornos de sono, doenças sistêmicas e uso contínuo de medicamentos. Métodos: foram avaliados 22 pacientes atendidos em nível ambulatorial através de escalas validadas e questionário sociodemográfico, seguido de medidas de fluxo salivar espontâneo e estimulado através do método de expectoração salivar. Na análise estatística descritiva foi utilizado SPSS 16.0. Resultados: a amostra foi composta por 4 homens e 18 mulheres com idade média de 61,6+2,83 anos. As médias de fluxo salivar espontâneo e estimulado foram 0,27+0,06 ml/min e 0,84+0,08 ml/min, respectivamente. A hipossalivação esteve presente em 54,5% dos casos, sendo que a xerostomia foi referida por 31,3% dos pacientes. Sintomas depressivos leves foram observados em 22,7% da amostra. Na avaliação de ansiedade-traço 31,8% apresentaram sintomas de ansiedade moderada, 63,6%, sintomas de ansiedade elevada e 4,5%, ansiedade muito elevada. Quanto à avaliação de ansiedade-estado 27,3% apresentaram sintomas de ansiedade moderada e 72,7% sintomas de ansiedade elevada. Setenta e sete por cento apresentaram alterações de sono. Os exames sorológicos não apresentaram alterações significativas. Conclusão: estes resultados sugerem associação entre os parâmetros comportamentais avaliados e os sintomas bucais, sendo necessário o aumento da amostra para que possamos confirmar estatisticamente essa tendência.

Aim: to evaluate factors associated with the diagnosis of burning mouth, such as dry mouth, hyposalivation, depressive symptoms, anxiety, sleep disorders, systemic diseases, and continuous use of medications. Methods: twenty-two patients recruited from outpatient clinics were assessed using validated scales and a sociodemographic questionnaire. Patients’ spontaneous and stimulated salivary flow rates were also measured using saliva expectoration. SPSS 16.0 was used in the descriptive statistical analysis. Results: the sample consisted of 4 men and 18 women whose mean age was 61.6±2.83 years. The mean of spontaneous and stimulated salivary flow rates were 0.27+0.06 mL/min and 0.84+0.08 mL/min, respectively. Hyposalivation was present in 54.5% of cases, and dry mouth was reported by 31.3% of patients. Mild depressive symptoms were observed in 22.7% of the sample. When assessing anxiety-trait, we found that 31.8% had moderate symptoms of anxiety, 63.6% had symptoms of high anxiety, and 4.5% had very high anxiety. The assessment of anxiety-status showed that 27.3% and 72.7% had moderate and elevated anxiety symptoms, respectively. Seventy-seven percent had sleep disorders. Serological tests showed no significant changes. Conclusion: Our findings suggest an association between the behavioral parameters evaluated and the oral symptoms, indicating the need for a larger sample to confirm this trend using statistical analysis.