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Maria da Graca-Tarragó,1,2 Mateus Lech,2 Letícia Dal Moro Angoleri,2 Daniela Silva Santos,2 Alícia Deitos,1,2 Aline Patrícia Brietzke,1,2 Iraci LS Torres,1,3 Felipe Fregni,4 Wolnei Caumo1,2,5,6 1Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 2Laboratory of Pain and Neuromodulation, HCPA, Porto Alegre, Brazil; 3Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 4Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA; 5Surgery Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 6Pain and Palliative Care Service, HCPA, Porto Alegre, Brazil Background: Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS). Objectives: We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes. Registration: The trial is registered in Clinical trials.gov: NCT01747070. Methods: Sixty women with KOA, aged 50–75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1–S2. Results: A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P

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

To study the characteristics of temporal summation (TS) and conditioned pain modulation (CPM) in fibromyalgia (FM) patients, we systematically searched Pubmed and EMBASE for studies using TS or CPM comparing FM patients with healthy controls. We computed Hedges' g, risk of bias, sensitivity analysis, and meta-regression tests with 10,000 Monte-Carlo permutations. Twenty-three studies (625 female and 23 male FM patients and 591 female and 81 male healthy controls) were included. The meta-analyses showed an effect size of .53 for TS (P .001; 95% confidence interval = .23-.83), which is a 68% relative difference between patients and controls, and of .57 for CPM (P .001; 95% confidence interval = -.88 to -.26), representing a 65% relative difference between the groups. The qualitative analyses revealed large heterogeneity between study protocols. Although studies were of low risk of bias, lack of blinding was substantial. Sensitivity analysis and meta-regression identified type and site of stimulation, age, lab, sample size, and medication control as important sources of between-study variability. We showed a significant alteration of pain modulation mechanisms in FM patients.This novel meta-analysis provides evidence for defective endogenous pain modulation in FM patients. We explored the effect of covariates on between-study variability in these paradigms. These biomarkers may aid in diagnosis, and treatment of patients. However, validation requires further investigation under strict methodological settings, and into individual patient covariates.

Chronic myofascial pain syndrome has been related to defective descending inhibitory systems. Twenty-four females aged 19 to 65 years with chronic myofascial pain syndrome were randomized to receive 10 sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). We tested if pain (quantitative sensory testing), descending inhibitory systems (conditioned pain modulation [quantitative sensory testing + conditioned pain modulation]), cortical excitability (TMS parameters), and the brain-derived neurotrophic factor (BDNF) would be modified. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analog scale on pain (analysis of variance, P.01). Post hoc analysis showed that compared with placebo-sham, the treatment reduced daily pain scores by -30.21% (95% confidence interval = -39.23 to -21.20) and analgesic use by -44.56 (-57.46 to -31.67). Compared to sham, rTMS enhanced the corticospinal inhibitory system (41.74% reduction in quantitative sensory testing + conditioned pain modulation, P.05), reduced the intracortical facilitation in 23.94% (P = .03), increased the motor evoked potential in 52.02% (P = .02), and presented 12.38 ng/mL higher serum BDNF (95% confidence interval = 2.32-22.38). No adverse events were observed. rTMS analgesic effects in chronic myofascial pain syndrome were mediated by top-down regulation mechanisms, enhancing the corticospinal inhibitory system possibly via BDNF secretion modulation.High-frequency rTMS analgesic effects were mediated by top-down regulation mechanisms enhancing the corticospinal inhibitory, and this effect involved an increase in BDNF secretion.

Background: Fibromyalgia (FM) is conceptualized as a central sensitization (CS) condition, that presents high serum brain-derived neurotrophic factor (BDNF) and neuroglia activation. Although the S100B protein regulates neuroglia functions, it has been traditionally used as a proxy of central nervous system damage. However, neither BDNF nor S100B association with the clinical picture of FM has been elucidated. To explore their association with the pressure-pain threshold (PPT) in FM, we performed a cross-sectional study, including 56 females with confirmed FM aged 18–65 years. Linear regression models were used to adjust for potential confounding factors between serum BDNF, S100B and PPT. Results: Serum BDNF and S100B were correlated (Spearman’s Rho = 0.29). Serum BDNF (log) and S100B (log) were correlated with the PPT (log) (Partial η2 = 0.129, P = 0.012 for the BDNF (log), and Partial η2 = 0.105, P = 0.025 for the S100B (log)). Serum BDNF (log) was inversely associated with PPT (log) (β = −1.01, SE = 0.41), age (β = −0.02, SE = 0.15) and obsessive compulsive disorder (β = −0.36, SE = 0.15), while serum S100B (log) was inversely associated with PPT (log) (β = −1.38, SE = 0.50), only. Conclusions: Both neuroglia key mediators in the CS process were inversely correlated with the PPT. Serum assessment of BDNF and S100B deserve further study to determine its potential as a proxy for the CS spectrum in FM.

Pain catastrophizing regularly occurs in chronic pain patients. It has been suggested that pain catastrophizing is a stable, person-based construct. These findings highlight the importance of investigating catastrophizing in conceptualizing specific approaches for pain management. One important area of investigation is the mechanism underlying pain catastrophizing. Therefore, this study explored the relationship between a neurophysiological marker of cortical excitability, as assessed by transcranial magnetic stimulation, and catastrophizing, as assessed by the Brazilian Portuguese Pain Catastrophizing Scale, in patients with chronic myofascial pain syndrome. The Pain Catastrophizing Scale is a robust questionnaire used to examine rumination, magnification and helplessness that are associated with the experience of pain. We include 24 women with myofascial pain syndrome. The Brazilian Portuguese Pain Catastrophizing Scale and cortical excitability were assessed. Functional and behavioral aspects of pain were evaluated with a version of the Profile of Chronic Pain scale and by multiple pain measurements (eg, pain intensity, pressure pain threshold, and other quantitative sensory measurements). Intracortical facilitation was found to be significantly associated with pain catastrophizing (β = .63, P = .001). Our results did not suggest that these findings were influenced by other factors, such as age or medication use. Furthermore, short intracortical inhibition showed a significant association with pressure pain threshold (β = .44, P = .04). This study elaborates on previous findings indicating a relationship between cortical excitability and catastrophizing. The present findings suggest that glutamatergic activity may be associated with mechanisms underlying pain catastrophizing; thus, the results highlight the need to further investigate the neurophysiological mechanisms associated with pain and catastrophizing. Perspective This study highlights the relationship between cortical excitability and catastrophizing. Cortical measures may illuminate how catastrophizing responses may be related to neurophysiological mechanisms associated with chronic pain.

OBJETIVO: Analisar fatores associados à Hipertensão Arterial Sistêmica (HAS) e sua relação com o estado nutricional de indivíduos hipertensos cadastrados no programa Hiperdia em um município do Rio Grande do Sul. MÉTODOS: Foram avaliados indivíduos hipertensos cadastrados no Hiperdia. Os dados referentes aos fatores associados à hipertensão foram coletados por meio de um questionário semiestruturado composto pelas seguintes variáveis: idade, escolaridade, exercício físico, tabagismo, medicamentos consumidos, herança genética, doenças crônicas, peso, altura e circunferência da cintura. RESULTADOS: Entre os 402 hipertensos estudados, 138 (34,3%) eram adultos e 264 (65,7%) eram idosos, sendo que a maioria era do gênero feminino. A prevalência de excesso de peso foi de 76,8% em adultos enquanto 35% dos idosos apresentaram peso normal. Quando comparadas as faixas etárias, 11% dos idosos estavam significativamente associados ao analfabetismo. Os adultos e idosos apresentaram média de circunferência da cintura e classificação do IMC acima dos níveis desejados. CONCLUSÃO: Neste estudo, a HAS foi associada a níveis pressóricos aumentados com o avanço da idade, excesso de peso, circunferência da cintura elevada, baixa escolaridade, fumo e consumo de bebida alcoólica. O excesso de peso configurou-se como um dos fatores mais agravantes nessa população.

Transcranial pulsed current stimulation (tPCS) and transcranial direct current stimulation (tDCS) are two noninvasive neuromodulatory brain stimulation techniques whose effects on human brain and behavior have been studied individually. In the present study we aimed to quantify the effects of tDCS and tPCS, individually and in combination, on cortical activity, sensitivity and pain-related assessments in healthy individuals in order to understand their neurophysiological mechanisms and potential applications in clinical populations. A total of 48 healthy individuals participated in this randomized double blind sham controlled study. Participants were randomized to receive a single stimulation session of either: active or sham tPCS and active or sham tDCS. Quantitative electroencephalography (qEEG), sensitivity and pain assessments were used before and after each stimulation session. We observed that tPCS had a higher effect on power, as compared to tDCS, in several bandwidths on various cortical regions: the theta band in the parietal region (p = 0.021), the alpha band in the temporal (p=0.009), parietal (p = 0.0063), and occipital (p < 0.0001) regions. We found that the combination of tPCS and tDCS significantly decreased power in the low beta bandwidth of the frontal (p = 0.0006), central (p = 0.0001), and occipital (p = 0.0003) regions, when compared to sham stimulation. Additionally, tDCS significantly increased power in high beta over the temporal (p = 0.0015) and parietal (p = 0.0007) regions, as compared to sham. We found no effect on sensitivity or pain-related assessments. We concluded that tPCS and tDCS have different neurophysiological mechanisms, elicit distinct signatures, and that the combination of the two leads to no effect or a decrease on qEEG power. Further studies are required to examine the effects of these techniques on clinical populations in which EEG signatures have been found altered. (C) 2016 Published by Elsevier Ireland Ltd., This research was supported by Labuschagne Foundation. Dr. Thibaut was founded by the Belgian American Educational Foundation (BAEF) and the Duesberg Foundation. Dr. Morales-Quezada received funding support from an Institutional National Research Service Award from the National Center for Complementary and Integrative Health grant T32AT000051, the Ryoichi Sasakawa Fellowship Fund, and by the Program in Placebo Studies at Beth Israel Deaconess Medical Center. Deitos, A. was founded by the Coordination for the Improvement of Higher Education Personnel - CAPES, International Cooperation General Program - PGCI (no 023/11). Prof. Fregni has been supported by NIH RO1 grant (1R01HD082302-01A1).

Morphine administration in the neonatal period can induce long-term effects in pain circuitry leading to hyperalgesia induced by the opioid in adult life. This study explored a new pharmacological approach for reversing this effect of morphine. We focused on melatonin owing its well-known antinociceptive and anti-inflammatory effects, and its ability to interact with the opioid system. We used the formalin test to assess the medium and long-term effects of melatonin administration on hyperalgesia induced by morphine in early life. Newborn rats were divided into two groups: the control group, which received saline, and the morphine group, which received morphine (5 μg subcutaneously [s.c.]) in the mid-scapular area, once daily for 7 days, from P8 (postnatal day 8) until P14. At postnatal days 30 (P30) and 60 (P60), both groups were divided in two subgroups, which received melatonin or melatonin vehicle 30 min before the formalin test. The nociceptive responses were assessed by analyzing the total time spent biting, flicking, and licking the formalin-injected hind paw; these responses were recorded during the first 5 min (neurogenic/acute phase) and from 15 to 30 min (inflammatory/tonic phase). Initially, animals in the morphine/vehicle group showed increased nociceptive behavior in phase II (inflammatory) of the formalin test at P30, and in the neurogenic and inflammatory phases at P60. These increased nociceptive responses were fully reversed by melatonin administration at either age. These findings show that melatonin administration is a potential means for countering hyperalgesia induced by neonatal morphine exposure in young and adult rats.

Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0–10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use. In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0–10) during CPM-task. A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0–10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index. These findings support the hypothesis that the change in cortical plasticity in KOACP is associated with less intracortical inhibition, as measured by the CSP. These results show that the neural change in the motor cortex in KOACP is associated with pain and disability levels, and also with decreased activation of the endogenous pain-modulating system by a CPM-task.

O objetivo deste estudo foi avaliar o estoque domiciliar de medicamentos em comunidades atendidas pela Estratégia de Saúde da Família (ESF) em município localizado no Sul do Brasil. Foram amostrados 10% dos domicílios de cinco ESF. Os dados foram coletados por Agentes Comunitários de Saúde (ACS) através de questionário adaptado. A idade média dos entrevistados foi de 42 anos e dos moradores foi de 16 anos, destes 51% eram mulheres. Foi observada renda de 1 a 3 salários mínimos (69,1%), e escolaridade de 0 a 4 anos de estudo (42%). Dos domicílios visitados, 98,7% apresentavam pelo menos um medicamento estocado. Dos 533 lugares de guarda averiguados, 43,5% estava exposto ao calor, 39,6% a umidade, 16,5% a luz. Dos 2.717 medicamentos encontrados, 6,9% estavam vencidos, 35,3% não estavam dentro da embalagem secundária, quando esta se aplica, 67,9% não continham a presença de bula. Os fármacos analgésicos foram os mais prevalentes no estoque (21%). Os resultados nos levam a concluir que há necessidade de equipe multiprofissional para a promoção de saúde e a racionalização dos estoques domiciliares de medicamentos, sendo que o ACS é um profissional indispensável para a promoção do uso racional de medicamentos.The scope of this study was to investigate the in-house stock of medication in communities served by the Family Health Strategy (FHS) in a city located in the south of Brazil. A sample of 10% of households in five FHS areas was studied. Data were collected by Community Healthcare Workers using the adapted Fernandes questionnaire (2000). The mean age of the interviewees was 42 years and of the residents was 16 years, 51% of which were female. Low income (1 to 3 minimum wages) was observed (69.1%), and low education levels (0 to 4 years of study) (42%). Of the households visited 98.7% had at least one medication in stock. In 533 of the storage places located, 43.5% of such places were exposed to heat, 39.6% were exposed to humidity and 16.51% to light. Of the 2,717 medicines found, 6.9% were past the validity date, 35.3% were not in the secondary wrapping and 67.9% were without the patient information leaflet. Analgesics were the most common medications in in-house stock (21%). This study revealed the need for a multi-professional team to promote health and the rationalization of in-house stock since the Community Healthcare Worker is an indispensable professional to promote the rational use of medication.

Pharmaceutical assistance concerns actions developed by the pharmacist and other professionals with the purpose of promoting, protecting and restoring health. Medications are an essential tool in this process that focuses on the access to, and the rational use of, drugs. This study is aimed at evaluating the Pharmaceutical Assistance provided by Municipal Health Offices in the Taquari Valley, Rio Grande do Sul. For this purpose, 2,794 users of public pharmacies were interviewed and data was analyzed using descriptive statistics. The users of the public pharmacies were mainly female and individuals with low educational level and income. On average, 2.41 drugs were prescribed per medical prescription and 1.72 of these were procured. Out of the total medicines prescribed, 76.5% were listed in the municipal standard drug list (SDL). Medication was prescribed by its generic name in 81.8% of the prescriptions. Antibiotics and injections were prescribed in 11.9% and 4.0% of the prescriptions, respectively. Users' access to information is partial, which can impair adherence to the treatment. Thus, it is possible to conclude that review of the service is necessary for it to be effective.A Assistência Farmacêutica se preocupa com ações desenvolvidas pelo farmacêutico ou outros profissionais com o propósito de promover, proteger e restaurar a saúde. Medicamentos são ferramentas essenciais nesse processo, que se concentra no acesso e no uso racional de fármacos. Este estudo objetivou a avaliação da Assitência Farmacêutica suprida pela Secretaria Municipal da Saúde no Vale do Taquari, no Rio Grande do Sul. Com esse propósito, 2.794 usuários das farmácias públicas foram entrevistados e analisaram-se os dados usando estatística descritiva. Os usuários das farmácias públicas eram, principalmente, mulheres e indivíduos com baixo nível educacional e financeiro. Na média, 2,41 fármacos eram prescritos por prescrição médica e 1,72 destes foram obtidos. Do total de medicamentos prescritos, 76,5% estava inscritos na lista de medicamentos padrão do município (SDL). A medicação foi prescrita pelo nome genérico em 81,8% dos casos. Antibióticos e injeções foram prescritas em 11,9% e 4,0% das prescrições, respectivamente. O acesso dos usuários à informação é parcial, o que pode prejudicar a adesão ao tratamento. Dessa forma, é possível concluir que a revisão do serviço é necessária para que seja eficaz.

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain. However, its neurobiological mechanisms are not entirely elucidated. Given the complex interaction between the networks involved in pain process, our approach, to providing insights into the neural mechanisms of pain, was to investigate the relationship between neurophysiological, neurochemical and clinical outcomes such as corticospinal excitability. Recent evidence has demonstrated that three neural systems are affected in chronic pain: (i) motor corticospinal system; (ii) internal descending pain modulation system; and (iii) the system regulating neuroplasticity. In this cross-sectional study, we aimed to examine the relationship between these three central systems in patients with chronic MPS of whom do/do not respond to the Conditioned Pain Modulation Task (CPM-task). The CPM-task was to immerse her non-dominant hand in cold water (0-1°C) to produce a heterotopic nociceptive stimulus. Corticospinal excitability was the primary outcome; specifically, the motor evoked potential (MEP) and intracortical facilitation (ICF) as assessed by transcranial magnetic stimulation (TMS). Secondary outcomes were the cortical excitability parameters [current silent period (CSP) and short intracortical inhibition (SICI)], serum brain-derived neurotrophic factor (BDNF), heat pain threshold (HPT), and the disability related to pain (DRP). We included 33 women, (18-65 years old). The MANCOVA model using Bonferroni's Multiple Comparison Test revealed that non-responders (n = 10) compared to responders (n = 23) presented increased intracortical facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater motor-evoked potential amplitude (μV) 1.93 (0.54) vs. 1.40 (0.27), as well a higher serum BDNF (pg/Ml) 32.56 (9.95) vs. 25.59 (10.24), (P < 0.05 for all). Also, non-responders presented a higher level of DRP and decreased HPT (P < 0.05 for all). These findings suggest that the loss of net descending pain inhibition was associated with an increase in ICF, serum BDNF levels, and DRP. We propose a framework to explain the relationship and potential directionality of these factors. In this framework we hypothesize that increased central sensitization leads to a loss of descending pain inhibition that triggers compensatory mechanisms as shown by increased motor cortical excitability.

Introduction: Pegylated Interferon Alpha (Peg-IFN) in combination with other drugs is the standard treatment for chronic hepatitis C infection (HCV) and is related to severe painful symptoms. The aim of this study was access the efficacy of transcranial direct current stimulation (tDCS) in controlling the painful symptoms related to Peg-IFN side effects. Materials and Methods: In this phase II double-blind trial, twenty eight (n = 28) HCV subjects were randomized to receive either 5 consecutive days of active tDCS (n = 14) or sham (n = 14) during 5 consecutive days with anodal stimulation over the primary motor cortex region using 2 mA for 20 min. The primary outcomes were visual analogue scale (VAS) pain and brain-derived neurotrophic factor (BDNF) serum levels. Secondary outcomes were the pressure-pain threshold (PPT), the Brazilian Profile of Chronic Pain: Screen (B-PCP:S), and drug analgesics use. Results: tDCS reduced the VAS scores (P < 0.003), with a mean pain drop of 56% (p < 0.001). Furthermore, tDCS was able to enhance BDNF levels (p < 0.01). The mean increase was 37.48% in the active group. Finally, tDCS raised PPT (p < 0.001) and reduced the B-PCP:S scores and analgesic use (p < 0.05). Conclusions: Five sessions of tDCS were effective in reducing the painful symptoms in HCV patients undergoing Peg-IFN treatment. These findings support the efficacy of tDCS as a promising therapeutic tool to improve the tolerance of the side effects related to the use of Peg-IFN. Future larger studies (phase III and IV trials) are needed to confirm the clinical use of the therapeutic effects of tDCS in such condition. Trial registration: Brazilian Human Health Regulator for Research with the approval number CAAE 07802012.0.0000.5327.

Objective. To determine if in knee osteoarthritis (KOA), one session of active electrical intramuscular stimulation (a-EIMS) compared with sham causes an effect on the motor cortex excitability parameters [motor evoked potential (MEP; the primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP)] and pain measurements [pain pressure threshold (PPT); visual analog scale (VAS) and change in numerical pain scale (NPS0-10) during the conditioned pain modulation (CPM)-task]. This study also set out to determine if serum brain-derived neurotrophic factor (BDNF) mediates the effect of treatment on the cortical spinal system as assessed by MEP and PPT. Design. Randomized clinical trial. Subjects and methods. Women with KOA, 50–75-years old received a 30-min session of either sham (n = 13) or a-EIMS (n = 13) with 2 Hz. The pain measures and excitability parameters were measured before and immediately after a-EIMS or sham. Results. The a-EIMS group compared with sham decreased the MEP by 31,67% [confidence interval (CI) 95%, 2.34–60.98]. For the secondary outcomes, the a-EIMS reduced the ICF and increased the CSP but not changed the SICI. The a-EIMS improved the pain reported on VAS, the PPT, and the score of the NPS (0–10) during the CPM-task The BDNF was negatively correlated with the PPT ( r = −0.56). Conclusions. The serum BDNF revealed an inverse relationship with PPT independent of the treatment group. These results suggest that a-EIMS enhanced the corticospinal inhibitory systems in cortical and infracortical pain processing sites most likely by bottom-up regulation mechanisms.

Objective. The aim was to assess the neuromodulation techniques effects (repetitive transcranial magnetic stimulation [rTMS] and deep intramuscular stimulation therapy [DIMST]) on pain intensity, peripheral, and neurophysiological biomarkers chronic myofascial pain syndrome (MPS) patients. Design. Randomized, double blind, factorial design, and controlled placebo-sham clinical trial. Setting. Clinical trial in the Laboratory of Pain and Neuromodulation at Hospital de Clinicas de Porto Alegre ([NCT02381171][1]). Subjects. We recruited women aged between 19- and 75-year old, with MPS diagnosis. Methods. Patients were randomized into four groups: rTMS + DIMST, rTMS + sham-DIMST, sham-rTMS + DIMST, sham-rTMS + sham-DIMST; and received 10 sessions for 20 minutes each one (rTMS and DIMST). Pain was assessed by visual analogue scale (VAS); neurophysiological parameters were assessed by transcranial magnetic stimulation; biochemical parameters were: BDNF, S100β, lactate dehydrogenase, inflammatory (TNF-α, IL6, and IL10), and oxidative stress parameters. Results. We observed the pain relief assessed by VAS immediately assessed before and after the intervention ( P 0.05). Conclusion. Our findings add additional evidence about rTMS and DIMST in relieving pain in MPS patients without synergistic effect. No peripheral biomarkers reflected the analgesic effect of both techniques; including those related to cellular damage. Additionally, one neurophysiological parameter (increased MEP amplitude) needs to be investigated. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02381171&atom=%2Fpainmedicine%2F17%2F1%2F122.atom

Background: Chronic tension-type headache (CTTH) is characterized by almost daily headaches and central sensitization, for which electroacupuncture (EA) might be effective. The central nervous system (CNS) plasticity can be tracked in serum using the brain-derived neurotrophic factor (BDNF), a neuroplasticity mediator. Thus, we tested the hypothesis that EA analgesia in CTTH is related to neuroplasticity indexed by serum BDNF. Methods: We enrolled females aged 18–60 years with CTTH in a randomized, blinded, placebo-controlled crossover trial, comparing ten EA sessions applied for 30 minutes (2–10 Hz, intensity by tolerance) in cervical areas twice per week vs. a sham intervention. Treatment periods were separated by two washout weeks. Pain on the 10-cm visual analog scale (VAS) and serum BDNF were assessed as primary outcomes. Results: Thirty-four subjects underwent randomization, and twenty-nine completed the protocol. EA was superior to sham to alleviate pain (VAS scores 2.38 ± 1.77 and 3.02 ± 2.49, respectively, P = 0.005). The VAS scores differed according to the intervention sequence, demonstrating a carryover effect (P < 0.05). Using multiple regression, serum BDNF was adjusted for the Hamilton depression rating scale (HDRS) and the VAS scores (r-squared = 0.07, standard β coefficients = −0.2 and −0.14, respectively, P < 0.001). At the end of the first intervention period, the adjusted BDNF was higher in the EA phase (29.31 ± 3.24, 27.53 ± 2.94 ng/mL, Cohen’s d = 0.55). Conclusion: EA analgesia is related to neuroplasticity indexed by the adjusted BDNF. EA modulation of pain and BDNF occurs according to the CNS situation at the moment of its administration, as it was related to depression and the timing of its administration.

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.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).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 was5 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%).Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Background: Central disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality. Methods: Sixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment. Results: Melatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P < 0.01). The delta values on the VAS scores were-12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin and melatonin+amitriptyline groups, respectively. Melatonin alone and in combination increased the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,-2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin + amitriptyline treated displayed better results than melatonin and amitriptyline alone in terms of FIQ and PPT improvement (P < 0.05, fort both). Conclusion: Melatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT. Trial registration: Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014.

Endometriosis-associated chronic pelvic pain (EACPP) presents with an intense inflammatory reaction. Melatonin has emerged as an important analgesic, antioxidant, and antiinflammatory agent. This trial investigates the effects of melatonin compared with a placebo on EACPP, brain-derived neurotrophic factor (BDNF) level, and sleep quality. Forty females, aged 18 to 45 years, were randomized into the placebo (n = 20) or melatonin (10 mg) (n = 20) treatment groups for a period of 8 weeks. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain, dysmenorrhea, dysuria, and dyschezia (analysis of variance, P < 0.01 for all analyses). Post hoc analysis showed that compared with placebo, the treatment reduced daily pain scores by 39.80% (95% confidence interval [CI] 12.88-43.01%) and dysmenorrhea by 38.01% (95% CI 15.96-49.15%). Melatonin improved sleep quality, reduced the risk of using an analgesic by 80%, and reduced BNDF levels independently of its effect on pain. This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin's ability to improve sleep quality. Additionally, the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms.

O objetivo deste estudo foi avaliar o estoque domiciliar de medicamentos em comunidades atendidas pela Estratégia de Saúde da Família (ESF) em município localizado no Sul do Brasil. Foram amostrados 10% dos domicílios de cinco ESF. Os dados foram coletados por Agentes Comunitários de Saúde (ACS) através de questionário adaptado. A idade média dos entrevistados foi de 42 anos e dos moradores foi de 16 anos, destes 51% eram mulheres. Foi observada renda de 1 a 3 salários mínimos (69,1%), e escolaridade de 0 a 4 anos de estudo (42%). Dos domicílios visitados, 98,7% apresentavam pelo menos um medicamento estocado. Dos 533 lugares de guarda averiguados, 43,5% estava exposto ao calor, 39,6% a umidade, 16,5% a luz. Dos 2.717 medicamentos encontrados, 6,9% estavam vencidos, 35,3% não estavam dentro da embalagem secundária, quando esta se aplica, 67,9% não continham a presença de bula. Os fármacos analgésicos foram os mais prevalentes no estoque (21%). Os resultados nos levam a concluir que há necessidade de equipe multiprofissional para a promoção de saúde e a racionalização dos estoques domiciliares de medicamentos, sendo que o ACS é um profissional indispensável para a promoção do uso racional de medicamentos.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that is affordable and easy to operate compared to other neuromodulation techniques. Anodal stimulation increases cortical excitability, while the cathodal stimulation decreases it. Although tDCS is a promising treatment approach for chronic pain as well as for neuropsychiatric diseases and other neurological disorders, several complex neurobiological mechanisms that are not well understood are involved in its effect. The purpose of this systematic review is to summarize the current knowledge regarding the neurobiological mechanisms involved in the effects of tDCS. The initial search resulted in 171 articles. After applying inclusion and exclusion criteria, we screened 32 full-text articles to extract findings about the neurobiology of tDCS effects including investigation of cortical excitability parameters. Overall, these findings show that tDCS involves a cascade of events at the cellular and molecular levels. Moreover, tDCS is associated with glutamatergic, GABAergic, dopaminergic, serotonergic, and cholinergic activity modulation. Though these studies provide important advancements toward the understanding of mechanisms underlying tDCS effects, further studies are needed to integrate these mechanisms as to optimize clinical development of tDCS.

The scope of this study was to investigate the in-house stock of medication in communities served by the Family Health Strategy (FHS) in a city located in the south of Brazil. A sample of 10% of households in five FHS areas was studied. Data were collected by Community Healthcare Workers using the adapted Fernandes questionnaire (2000). The mean age of the interviewees was 42 years and of the residents was 16 years, 51% of which were female. Low income (1 to 3 minimum wages) was observed (69.1%), and low education levels (0 to 4 years of study) (42%). Of the households visited 98.7% had at least one medication in stock. In 533 of the storage places located, 43.5% of such places were exposed to heat, 39.6% were exposed to humidity and 16.51% to light. Of the 2,717 medicines found, 6.9% were past the validity date, 35.3% were not in the secondary wrapping and 67.9% were without the patient information leaflet. Analgesics were the most common medications in in-house stock (21%). This study revealed the need for a multi-professional team to promote health and the rationalization of in-house stock since the Community Healthcare Worker is an indispensable professional to promote the rational use of medication.

Das chronische myofasziale Schmerzsyndrom ist eine haufige Ursache von Schmerzen des Bewegungsapparats und mit einem Defizit absteigender hemmender Leitungsbahnen verbunden. Eine Moglichkeit, die intrakortikalen hemmenden Leitungsbahnen zu stimulieren, ist die repetitive transkranielle Magnet-Stimulation (rTMS).