Methadone in post-herpetic neuralgia: A pilot proof-of-concept study

OBJECTIVE: This research was designed as a pilot proof-of-concept study to evaluate the use of low-dose methadone in post-herpetic neuralgia patients who remained refractory after first and second line post-herpetic neuralgia treatments and had indications for adding an opioid agent to their current drug regimens. METHODS: This cross-over study was double blind and placebo controlled. Ten opioid naïve post-herpetic neuralgia patients received either methadone (5 mg bid) or placebo for three weeks, followed by a 15-day washout period and a second three-week treatment with either methadone or placebo, accordingly. Clinical evaluations were performed four times (before and after each three-week treatment period). The evaluations included the visual analogue scale, verbal category scale, daily activities scale, McGill pain questionnaire, adverse events profile, and evoked pain assessment. All patients provided written informed consent before being included in the study. ClinicalTrials.gov: NCT01752699 RESULTS: Methadone, when compared to placebo, did not significantly affect the intensity of spontaneous pain, as measured by the visual analogue scale. The intensity of spontaneous pain was significantly decreased after the methadone treatment compared to placebo on the category verbal scale (50% improved after the methadone treatment, none after the placebo, p = 0.031). Evoked pain was reduced under methadone compared to placebo (50% improved after the methadone treatment, none after the placebo, p = 0.031). Allodynia reduction correlated with sleep improvement (r = 0.67, p = 0.030) during the methadone treatment. The side effects profile was similar between both treatments. Conclusions: Methadone seems to be safe and efficacious in post-herpetic neuralgia. It should be tried as an adjunctive treatment for post-herpetic neuralgia in larger prospective studies

Dissecting central post-stroke pain:a controlled symptom-psychophysical characterization

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8–41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (ρ = −0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ = −0.4; P = 0.008) and heat pain thresholds (ρ = 0.5; P = 0.003), burning pain with mechanical detection (ρ = −0.4; P = 0.015) and mechanical pain thresholds (ρ = −0.4, P < 0.013), evoked pain with mechanical pain threshold (ρ = −0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials

Neuropathic pain after brachial plexus avulsion - central and peripheral mechanisms

Abstract\ud \ud Review\ud The pain that commonly occurs after brachial plexus avulsion poses an additional burden on the quality of life of patients already impaired by motor, sensory and autonomic deficits. Evidence-based treatments for the pain associated with brachial plexus avulsion are scarce, thus frequently leaving the condition refractory to treatment with the standard methods used to manage neuropathic pain. Unfortunately, little is known about the pathophysiology of brachial plexus avulsion. Available evidence indicates that besides primary nerve root injury, central lesions related to the abrupt disconnection of nerve roots from the spinal cord may play an important role in the genesis of neuropathic pain in these patients and may explain in part its refractoriness to treatment.\ud \ud \ud Conclusions\ud The understanding of both central and peripheral mechanisms that contribute to the development of pain is of major importance in order to propose more effective treatments for brachial plexus avulsion-related pain. This review focuses on the current understanding about the occurrence of neuropathic pain in these patients and the role played by peripheral and central mechanisms that provides insights into its treatment.\ud \ud \ud Summary\ud Pain after brachial plexus avulsion involves both peripheral and central components; thereby it is characterized as a mixed (central and peripheral) neuropathic pain syndrome.Department of Neurology and by the Transcranial Magnetic Stimulation Laboratory of the Psychiatry Institute, University of São Paul

Assessment and treatment of patients with atypical facial pain patients that underwent repetitive transcranial magnetic stimulation

Dor facial atípica (DFA) é uma condição álgica crônica destacada pela etiopatogenia ainda desconhecida e pela característica rebelde aos tratamentos vigentes. O objetivo deste estudo é avaliar o limiar e padrões de excitabilidade cortical de doentes com DFA através de Estimulação Magnética Transcraniana (EMT) e compará-los a controles saudáveis, além de avaliar a eficácia terapêutica da EMT repetitiva (EMTr) ativa em doentes com DFA comparados à EMTr placebo. Durante o período de março de 2010 a dezembro de 2013 foram avaliados 29 doentes com DFA - os quais preencheram os critérios segundo a classificação proposta pela Associação Internacional de Cefaleia (2004) - e 28 controles saudáveis. A avaliação foi iniciada com a investigação da excitabilidade cortical bilateral. Em seguida, os doentes foram aleatorizados em dois grupos (ativo e placebo) para o tratamento com EMTr sobre o córtex motor primário na área de representação da face, esquematizado da seguinte forma: cinco sessões consecutivas para a fase de indução, e uma sessão semanal (pelo período de oito semanas) para a de manutenção; frequência excitatória de 10Hz; 80% do limiar motor de repouso; e 3000 pulsos no total por sessão. Os doentes foram avaliados quanto às características dolorosas no momento basal, no dia sete após a semana de indução, e nos dias 21, 30 e 60 para acompanhamento na fase de manutenção. Em todas as avaliações, utilizou-se os seguintes questionários validados para a língua portuguesa: Inventário Breve de Dor; DN4, Inventário de Sintomas de Dor Neuropática, Questionário de descritores breve de dor McGill e Questionário de qualidade de vida SF-36. Os doentes do grupo ativo e placebo apresentaram excitabilidade cortical inicial diferenciada em relação aos controles nos padrões de inibição e facilitação intracortical (p < 0,001). Ao final da última avaliação, os doentes do grupo ativo apresentavam padrões de excitabilidade cortical mais próximos dos controles do que os doentes do grupo placebo, embora sem significância estatística. Não houve diferença entre os grupos ativo e placebo em todas as avaliações quanto às características de dor e de qualidade de vida, sendo que ambos apresentaram melhora da dor. Conclui-se que há diferenças neurofisiológicas entre os doentes com DFA e os controles, e que isso pode ser modificado através do EMTr. A ausência de efeito terapêutico da EMTr neste estudo indica que mais estudos utilizando-se outros parâmetros para a verificação da eficácia da EMTr na DFA são necessáriosAtypical facial pain (AFP) is a chronic condition with unknown physiopathology and refractory characteristics to the gold standard treatment. The aim this study was to compare the patterns of cortical excitability between AFP and health subjects (HS), and to assess the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in AFP patients. Twenty-eight HS and 29 patients with AFP were included according to the IHS criteria (2004). Participants underwent a cortical excitability battery bilaterally in the primary motor cortex (M1) representation of the masseter muscle. They were then randomized into active and sham rTMS groups. rTMS was performed over the contralateral motor cortex in the representation area of the face daily for a week and weekly for eight weeks in a total of 13 sessions (5 induction and 8 maintenance sessions). All participants received 10 Hz rTMS, at 80% of the rest motor threshold (total of 3000 pulses per session). Sham rTMS was performed with an identical sham coil that emitted a similar sound to the active one. Patients were clinically assessed at baseline, after the induction phase (one week) and after 21, 30 and 60 days after the beginning of the study. Evaluations included the following validated questionnaires to the Brazilian Portuguese language: brief pain inventory; DN-4; Neuropathic pain symptoms inventory, McGill pain questionnaire brief version and quality of life questionnaire SF-36. At the baseline assessment, patients with AFP showed defective intracortical excitability inhibition and facilitation (p < 0.001) compared to HS. After the final evaluation, the patients from the active group had cortical excitability patterns closer to HS than the patients from the sham group, although there was no significant difference. There was no difference between patients that underwent active and sham rTMS about their pain characteristics and quality of life; both had pain improvement. In conclusion, there are neurophysiological differences between patients with AFP and HS, which could be modified with rTMS. The absence of a therapeutic effect of rTMS on pain in this study indicates the need of more research with other TMS parameters to check the efficacy of rTMS in AF

Envelhecimento bem-sucedido e vulnerabilidade em saúde : aproximações e perspectivas.

Tomando como referência a natureza multidimensional e dinâmica do conceito de vulnerabilidade em saúde, o objetivo deste artigo foi promover uma discussão sobre o que vem a ser envelhecer de forma bem-sucedida mesmo na presença de vulnerabilidades. Foram selecionados estudos que discutiram dimensões da vulnerabilidade no contexto da velhice, problematizando os recursos pessoais, sociais, programáticos e comunitários que poderiam tornar as pessoas idosas menos vulneráveis em face das situações de dependência e capacidade funcional reduzida. Embora pouco aplicada no campo da Gerontologia, a articulação entre o conceito de vulnerabilidade em saúde e o envelhecimento saudável e bem-sucedido parece ser produtiva e precisa ser melhor explorada.Considering the multidimensional and dynamic nature of the concept of health vulnerability, this article aimed to promote a discussion about the meaning of aging successfully even in the presence of vulnerabilities. We have selected studies which discussed dimensions of vulnerability in the context of old age, exploring personal, social, programmatic and community resources that could make older adults be less vulnerable in situations of dependence and reduced functional capacity. The articulation of the concept of health vulnerability and successful and healthy aging seems to be productive and should be further explored

Envejecimiento feliz y vulnerabilidad en salud: aproximaciones y perspectivas

Tomando como referência a natureza multidimensional e dinâmica do conceito de vulnerabilidade em saúde, o objetivo deste artigo foi promover uma discussão sobre o que vem a ser envelhecer de forma bem-sucedida mesmo na presença de vulnerabilidades. Foram selecionados estudos que discutiram dimensões da vulnerabilidade no contexto da velhice, problematizando os recursos pessoais, sociais, programáticos e comunitários que poderiam tornar as pessoas idosas menos vulneráveis em face das situações de dependência e capacidade funcional reduzida. Embora pouco aplicada no campo da Gerontologia, a articulação entre o conceito de vulnerabilidade em saúde e o envelhecimento saudável e bem-sucedido parece ser produtiva e precisa ser melhor explorada.Considering the multidimensional and dynamic nature of the concept of health vulnerability, this article aimed to promote a discussion about the meaning of aging successfully even in the presence of vulnerabilities. We have selected studies which discussed dimensions of vulnerability in the context of old age, exploring personal, social, programmatic and community resources that could make older adults be less vulnerable in situations of dependence and reduced functional capacity. The articulation of the concept of health vulnerability and successful and healthy aging seems to be productive and should be further explored.Tomando como referencia la naturaleza multi-dimensional y dinámica del concepto de vulnerabilidad en salud, el objetivo de este artículo es el promover una discusión sobre lo que viene a ser envejecer con éxito incluso en presencia de vulnerabilidades. Se han seleccionado estudios que discuten dimensiones de vulnerabilidad en el contexto de la vejez, encarando la problemática de los recursos personales, sociales, programáticos y comunitarios que podrían tornar a las personas ancianas menos vulnerables ante situaciones de dependencia y capacidad funcional reducida. Aunque poco aplicada en el campo de la Gerontología, la articulación del concepto de vulnerabilidad en salud y el envejecimiento saludable y feliz parece ser productiva y ha de ser mejor utilizada

Envejecimiento exitoso: trayectorias de un constructo y nuevas fronteras

Este artigo enfoca diferentes concepções de envelhecimento bem-sucedido, enfatizando o processo de envelhecimento como uma experiência heterogênea, que implica diferentes estratégias para a obtenção de bem-estar e qualidade de vida. Foram selecionados estudos que valorizam o processo de envelhecimento como parte do curso de vida humano, o papel da subjetividade e a auto-avaliação em saúde, como conceitos-chave para compreender o bem-estar e saúde na velhice. Os dados da literatura sugerem que a experiência do envelhecimento bem-sucedido valoriza a percepção dos próprios idosos, protagonistas de intervenções e dotados de julgamentos sobre bem-estar e qualidade de vida. Mesmo na presença de co-morbidades e diminuição da funcionalidade é possível identificar idosos que referem altos níveis de satisfação e boa qualidade de vida. Propomos questões que buscam aprimorar investigações e a elaboração deste constructo em gerontologia, tendo em vista a amplitude e complexidade do tema.This article focuses on different conceptions of successful aging, emphasizing the process of aging as a heterogeneous experience that implies different strategies for achieving wellbeing and quality of life. Studies valuing the aging process as part of the course of human life and the role of subjectivity and health self-perception, as key concepts for understanding wellbeing and health in old age, were selected. Data in the literature suggest that the experience of successful aging values elderly people's own perceptions: they are the protagonists of interventions and possess judgment about wellbeing and quality of life. Even in the presence of comorbidities and diminished functional ability, it is possible to identify elderly people who report high levels of satisfaction and good quality of life. We propose questions that seek to improve investigations and elaborate this construct within gerontology, bearing in mind the size and complexity of this topic.Este artículo aborda diferentes concepciones de envejecimiento bien llevado, enfatizando el proceso como una experiencia heterogénea que implica diferentes estrategias para la obtención del bienestar y calidad de vida; seleccionando estudios que evalúan el proceso de envejecimiento como parte del curso de vida humana, el papel de la subjetividad y la auto-evaluación en salud como conceptos clave para abarcar el bienestar y la salud en la vejez. Los datos obtenidos sugieren que este proceso resalta la percepción de los ancianos protagonistas de intervenciones. Proponemos cuestiones que tratan de perfeccionar investigaciones y la elaboración de este constructo en Gerontología