Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms / 神经科学通报·英文版

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Efeitos da estimulação transcraniana por corrente contínua sobre a dor e capacidade funcional em mulheres acometidas por chukungunya: um ensaio clínico randomizado / Effects of transcranial direct current stimulation on pain and functional capacity in women affected by chukungunya: a randomized clinical trial

A Chikungunya é uma afecção que tem atingido milhares de brasileiros, com números alarmantes de casos graves e incapacitantes em todo território nacional. É transmitida pelo mosquito Aedes Aegypti e causa febre de início agudo, dores articulares e musculares. A persistência dos sintomas de dor articular contínua e incapacitante tem sido considerada uma forte preocupação para a saúde pública, em virtude do comprometimento funcional e laboral que tem causado a população. Ainda não existe um tratamento específico para os casos de dor crônica causada pela Chikungunya e os mecanismos responsáveis pela cronificação das dores podem estar envolvidos com mecanismos centrais de controle da dor. Técnicas de neuromodulação poderiam atuar sobre esses efeitos e dentre elas existe a Estimulação Transcraniana por Corrente Continua (ETCC), que é uma técnica de aplicação de correntes de baixa intensidade sobre o escalpo com o intuito de modular a excitabilidade de áreas corticais envolvidas no processamento da dor crônica e tem se mostrado eficiente no tratamento desses casos. O objetivo desse estudo foi analisar o efeito da ETCC sobre as dores crônicas e capacidade funcional em mulheres acometidas por Chikungunya. Realizouse um estudo do tipo ensaio clínico randomizado, composto por mulheres com idade entre 28 e 70 anos, divididas em dois grupos experimental (ETCC) e placebo (SHAM). Foram avaliadas as características sociodemográficas e clínicas dos participantes, bem como o nível de capacidade funcional e sintomatologia dolorosa antes e após serem submetidos a seis sessões de ETCC em dias não consecutivos. Participaram do estudo 59 mulheres, com média de idade de 52,85 ±10,76 anos e o tempo de acometimento da doença apresentou uma média de 21,54 ±3,53 meses. Pode-se concluir com esse estudo que a ETCC foi efetiva para a redução das dores crônicas provenientes de indivíduos acometidos por Chikungunya (p< 0,007) a curto prazo, porém não foi capaz de alterar a capacidade funcional e interferência das dores no seu dia-a-dia. Sugere-se que outros estudos dessa natureza possam contemplar um tempo maior de acompanhamento do comportamento das dores crônicas nesse público e associar a ETCC a outros recursos terapêuticos para observar seus efeitos isolados e combinados (AU).

Chikungunya is a condition that has reached thousands of Brazilians, with alarming numbers of serious and incapacitating cases throughout the country. It is transmitted by the Aedes Aegypti mosquito and causes acute onset fever, joint and muscle pain. The persistence of symptoms of continuous and disabling joint pain has been considered a strong concern for public health, due to the functional and labor compromise that has caused the population. There is still no specific treatment for cases of chronic pain caused by Chikungunya and the mechanisms responsible for chronic pain can be involved with central mechanisms of pain control. Neuromodulation techniques could act on these effects and among them there is Transcranial Direct Current Stimulation (TDCS), which is a technique of applying currents of low intensity on the scalp in order to modulate the excitability of cortical areas involved in the processing of chronic pain and has been shown to be efficient in the treatment of these cases. The objective of this study was to analyze the effect of TDCS on chronic pain and functional capacity in women affected by Chikungunya. A randomized clinical trial, consisting of women aged 28 to 70 years, divided into two experimental groups (GTDCS) and placebo (GSHAM) was performed. The sociodemographic and clinical characteristics of the participants were evaluated, as well as the level of functional capacity and pain symptomatology before and after being submitted to six sessions of TDCS on non-consecutive days. A total of 59 women participated in the study, with a mean age of 52.85 ± 10.76 years and the time of disease involvement presented a mean of 21.54 ± 3.53 months. It can be concluded from this study that the ETCC was effective for the reduction of chronic pain from individuals affected by Chikungunya (p <0.007) in the short term, but it was not able to change the functional capacity and interference of the pains in their day- to-day. It is suggested that other studies of this nature may contemplate a greater time of monitoring the behavior of chronic pain in this public and associate CTEF with other therapeutic resources to observe its isolated and combined effects (AU).

Importancia de las co-morbilidades en la insuficiencia cardiaca / Importance of the co morbidities in the heart failure

La insuficiencia cardíaca afecta aproximadamente a 5.1 millones de adultos en los Estados Unidos de América, con expectativas de alcanzar a casi 8 millones de adultos para 2030. Los pacientes portadores de insuficiencia cardiaca están en mayor riesgo de sufrir una mayor morbilidad y mortalidad que la población en general; además, existen co-morbilidades que pueden complicar el cuidado de estos pacientes. La diabetes mellitus, el dolor crónico y la depresión son diagnósticos que muy a menudo coexisten con la insuficiencia cardiaca. Los medicamentos con que normalmente se tratan estas co-morbilidades pueden inducir o empeorar los síntomas de la insuficiencia cardiaca, así que determinar la terapia apropiada es de vital importancia. Los médicos deben entender la relación que existe entre estas medicaciones y la insuficiencia cardiaca para mejorar la asistencia, aumentar la seguridad del paciente y reducir la morbilidad y mortalidad. Este trabajo analiza la asociación entre ciertos medicamentos usados para el tratamiento de estas co-morbilidades y su relación con la insuficiencia cardiaca. El propósito de este artículo es proporcionar una orientación farmacológica donde las opciones de tratamiento tengan especial consideración con un aumento de la supervisión médica, para evitar la descompensación o aparición de la insuficiencia cardiaca en los pacientes portadores de diabetes mellitus, dolor crónico y depresión (AU).

Heart failure affects approximately 5.1 million adults in the USA, with expectations of a rise to nearly 8 million adults by 2030. Patients with heart failure are at increased risk for morbidity/mortality, and co-morbidities can further complicate care for these patients. Diabetes mellitus, chronic pain, and depression are diagnoses that often coexist with heart failure. Medications commonly used to treat these co-morbidities may induce or worsen heart failure symptoms, so determining appropriate drug therapy is important. Healthcare providers must understand the relationship between these medications and heart failure in order to improve prescribing practices to increase patient safety and reduce morbidity and mortality. This manuscript discusses the association between certain medications used to treat the aforementioned diagnoses and their relationship to heart failure. The purpose of this article is to provide guidance on which pharmacologic options require special consideration, increased monitoring, or complete avoidance in heart failure patients with diabetes mellitus, chronic pain, and/or depression (AU).

Síndrome do impacto do tornozelo na ressonância magnética: ensaio iconográfico / Magnetic resonance imaging of ankle impingement syndrome: iconographic essay

A síndrome do impacto do tornozelo é uma condição dolorosa causada por atrito de tecidos articulares, que é tanto causa quanto consequência de uma biomecânica alterada desta articulação. A sua principal causa são as lesões pós-traumáticas, principalmente lesões ligamentares, resultando em dor crônica no tornozelo. Do ponto de vista anatômico e clínico, estas síndromes são classificadas em: ântero-lateral, anterior, ântero-medial, póstero-medial e posterior. A ressonância magnética é um ótimo método diagnóstico para demonstrar as alterações ósseas e as partes moles dos vários tipos de impacto do tornozelo, fornecendo dados que auxiliam não só na comprovação desse diagnóstico, como na diferenciação com outras causas de dor articular. Os autores objetivam ilustrar os principais achados de ressonância magnética na síndrome do impacto do tornozelo.

Ankle impingement syndrome is a painful condition resulting from friction of joint tissues that is both cause and effect of an altered joint biomechanics. The leading causes of such condition are post-traumatic lesions, particularly the ligamentous ones, resulting in chronic ankle pain. From an anatomic and clinical point of view, these syndromes may be classified as anterolateral, anterior, anteromedial, posteromedial, and posterior. Magnetic resonance imaging is an excellent diagnostic method for demonstrating bone and soft tissue abnormalities resulting from different types of ankle impingement, providing useful data to confirm the diagnosis as well as to rule out other possible causes of joint pain. The present essay is aimed at illustrating the main magnetic resonance imaging findings in ankle impingement syndrome.