A proteína quinase dependente de RNA (PKR) é uma molécula sentinela ativada em situações de estresse celular, incluindo infecções virais. A ativação de PKR por meio de sua fosforilação aciona cascatas de sinalização intracelular envolvidas em respostas inflamatórias e inibição da síntese protéica. Dados prévios do nosso laboratório sugerem que PKR está envolvida na hiperalgesia térmica de origem inflamatória. No presente estudo, foi investigado o papel da PKR na hiperalgesia térmica induzida pelo vírus da herpes simples tipo 1 (HSV1), durante as fases herpética e pós-herpética, combinando métodos comportamentais, genéticos, farmacológicos e moleculares. Camundongos C57bl/6, PKR+/+ e PKR-/- machos foram inoculados com HSV1. Os grupos controle foram inoculados com HSV1 inativo. Alodínia mecânica e hiperalgesia térmica foram monitoradas antes da inoculação do vírus e 8, 14, 21 e 28 dias após a inoculação. A curva dose e temporesposta e o teste da capsaicina foram realizados no 8º e 21º dias após a inoculação do vírus. Também nos períodos herpético e pós-herpético, foi investigado o perfil de expressão de proteínas envolvidas nas vias de sinalização de PKR (PKR, eIF2?, PACT, IKK e PP2A?), assim como o efeito da inibição de PKR pelo monitoramento da fosforilação de PKR, IKK?/?, P38, JNK, ERK1,2 e STAT3, e expressão de CaMKII? e TRPV1 nos GRD (L3-L6) ipsilateralmente à pata inoculada. Alodínia mecânica e hiperalgesia térmica ficaram evidentes até 28 dias após a inoculação. Camundongos PKR-/- desenvolveram alodínia mecânica, mas não hiperalgesia térmica, quando comparados com animais PKR+/+. A inibição sistêmica de PKR reverteu a hiperalgesia térmica de modo tempo- e dose-dependente e preveniu o comportamento nocifensivo induzido por capsaicina, enquanto PKR-/- apresentaram resposta nocifensiva praticamente ausente em ambas as fases herpética e pósherpética. Houve aumento da expressão de PP2A? e da fosforilação de PKR, IKK?/? e eIF2?, durante os períodos herpético e pós-herpético, e de PACT na fase pósherpética. A inibição de PKR promoveu o aumento da fosforilação de P38 em ambas as fases, e redução da fosforilação de PLC?1 acompanhada do retorno da fosforilação de Akt e STAT3 ao nível do grupo controle e o aumento da expressão de Ca-MKII? na fase herpética. Já na fase pós-herpética, reduziu a fosforilação de JNK e Akt e a expressão de Ca-MKII?, retornou a fosforilação de ERK1,2, PLC?1 e STAT3 ao nível do grupo controle e aumentou a expressão de TRPV1. Nossos resultados indicam que a atividade de PKR desempenha papel essencial na hiperalgesia térmica induzida por infecção pelo HSV1 / Double stranded RNA-activated protein kinase (PKR) is a sentinel molecule activated by cellular stress conditions, including viral infections. PKR activation by phosphorylation triggers cascades involved in inflammatory response and protein synthesis suppression. Our previous data suggest that PKR is involved in the inflammatory thermal hyperalgesia. Here we investigated the role played by PKR on thermal hyperalgesia induced by herpes simplex virus type-1 (HSV-1), during herpetic and post-herpetic phases, by combining behavioral, genetic, pharmacological, and molecular methods. Adult male C57bl/6, PKR+/+ and PKR-/- mice were inoculated with HSV-1. Control groups were inoculated with inactive (mock) HSV1. Mechanical allodynia and thermal hyperalgesia were monitored before virus inoculation and 8, 14, 21, and 28 days post-inoculation. The dose- and timeresponse curve and the capsaicin test were performed at 8th and 21st days post virus inoculation. Also in the herpetic and post-herpetic periods, was investigated the expression profile of proteins involved in the PKR signaling pathways (PKR, eIF2?, PACT, IKK and PP2A?), and the effect of PKR inhibition by monitoring PKR, IKK?/?, P38, JNK, ERK1,2, and STAT3 phosphorylation, and Ca-MKII? and TRPV1 expression in the dorsal root ganglia (L3-L6) ipsilaterally to the inoculated paw. Mechanical allodynia and thermal hyperalgesia became evident until 28 days postinnoculation. PKR-/- mice developed mechanical allodynia but not thermal hyperalgesia, when compared with PKR+/+ mice. Systemic PKR inhibition reversed thermal hyperalgesia in a dose and time-dependent manner, and prevented the capsaicin-induced nocifensive behavior, whereas PKR-/- showed no nocifensive behavior almost absent in both herpetic and post-herpetic phases. There was increased expression of PP2A? and the phosphorylation of PKR, IKK?/?, and eIF2?, during herpetic and post-herpetic periods, and PACT in the post-herpetic phase. PKR inhibition increased P38 phosphorylation in both phases, and reduction of PLC?1 phosphorylation together with the return of the Akt and STAT3 phosphorylation to the control group level, and enhanced Ca-MKII? expression in the herpetic phase. At the post-herpetic phase, suppressed JNK and Akt, and Ca-MKII? expression returned ERK1,2, PLC?1 and STAT3 phosphorylation to control group level and increased TRPV1 expression. The data indicate that PKR activity plays an essential role in the HSV-1 infection-induced thermal hyperalgesia

Introdução: A asma e a DPOC são doenças crônicas inflamatórias que afetam a qualidade de vida dos pacientes. O tratamento medicamentoso é feito, em sua maioria, por via inalatória utilizando para isso os dispositivos inalatórios. O uso incorreto dos dispositivos inalatórios diminui a eficácia dos medicamentos, o que pode ocasionar a não aderência dos pacientes ao tratamento. Vários tipos de programas educativos para asma e DPOC têm sido desenvolvidos, diferenciando-se quanto à forma de abordagem, à situação em que a doença é atendida e aos desfechos considerados. O farmacêutico por meio de um programa educacional pode orientar os pacientes sobre a técnica correta dos dispositivos inalatórios e auxiliar este paciente na adesão ao tratamento. Objetivos: Realizar a compilação e sistematização dos resultados dos trabalhos apresentados pelo programa de atenção farmacêutica aos pacientes asmáticos e portadores de DPOC do ICHC FMUSP e do programa de pós-graduação de Fisiopatologia Experimental. Método: estudo retrospectivo e descritivo dos trabalhos de conclusão dos alunos do Curso de Aprimoramento Profissional em Farmácia Hospitalar e Introdução a Farmácia Clínica da Divisão de Farmácia do ICHC FMUSP e do programa de pós-graduação de Fisiopatologia Experimental da Faculdade de Medicina da USP. Estes estudos desenvolveram a temática da atenção farmacêutica e educação em asma e em DPOC, apresentados entre os anos de 2004 a 2012 que não tiveram artigos ou capítulos de livros publicados. Resultados: Foram enviados três capítulos para publicação no livro Atenção Farmacêutica - Gestão e Prática do HCFMUSP e um artigo será publicado no Jornal Brasileiro de Pneumologia. Conclusão: Publicações acadêmicas com o tema atenção farmacêutica ao paciente portador de doenças respiratórias crônicas demonstram a importânica da orientação/ educação desses pacientes quanto ao tratamento de suas doenças respiratórias / Introduction: Asthma and COPD are chronic inflammatory diseases that affect the quality of life of patients. Drug treatment is done mostly by inhalation, using for it inhalation devices. Incorrect use of inhalers decreases the effectiveness of medications which can cause non-adherence of patients to treatment. Various types of educational programs for asthma and COPD have been developed, differing on the mode the approach, the situation in which the disease is answered and the outcomes considered. The pharmacist through an educational program can educate patients about the proper technique of inhalation devices and assisting the patient to adhere to treatment. Objectives: Perform the compilation and systematization from studies data submitted by the pharmaceutical care program for patients with asthma and COPD developed by pharmacists from course of improvement of the Division of Pharmacy ICHC USP and also by the program of graduate Experimental Pathophysiology, Faculty of Medicine, USP. Method: A retrospective, descriptive study with the outcomes of studies of the students that completed the course in Professional Development Course in Hospital Pharmacy and Introduction to Clinical Pharmacy, of Division of Pharmacy of ICHC USP and the program graduate in Experimental Pathophysiology, Faculty of Medicine of USP. The studies show the theme of pharmaceutical care and asthma education and COPD, submitted between the years 2004 to 2012 and who had no articles or book chapters related books published. Results: three book chapters were sent for publication in the book Pharmaceutical Care - Management and Practice HC FMUSP and one article will be published in the Brazilian Journal of Pulmonology. Conclusion: academic publications on the theme pharmaceutical care to patients with chronic respiratory diseases shows the importance orientation/education of patients regarding the treatment of their respiratory diseases

INTRODUÇÃO: A dor vertebral apresenta significativo impacto econômico e social. Estimativas mais recentes do Global Burden of Diseases relatam que as algias vertebrais crônicas (AC) são a principal causa de anos vividos com incapacidade no mundo. A prevalência de algias vertebrais ao longo da vida varia entre 54% e 80%. OBJETIVOS: Estimar a prevalência de algias vertebrais crônicas e identificar fatores associados em uma amostra de pessoas com 15 anos ou mais de idade em um segmento da população da cidade de São Paulo, Brasil. MÉTODO: Foi realizado um estudo de corte transversal. Um total de 826 participantes foi selecionado para entrevistas domiciliares entre dezembro de 2011 e fevereiro de 2012. Foram utilizados a Escala Hospitalar de Ansiedade e Depressão (HADS), o Teste de Fagerström para Dependência de Nicotina (FTND), o Teste para Identificação de Problemas Relacionados ao uso de Álcool (AUDIT), a Escala EuroQol-5D e o Critério de Classificação Econômica Brasil (CCEB). RESULTADOS: A prevalência de AC foi estimada em 22% (IC 95%, 19,3 - 25,0). Os seguintes fatores foram considerados independentemente associados a AC: sexo feminino, 30 ou mais anos de idade, quatro anos ou menos de escolaridade, sintomas compatíveis com ansiedade e esforço físico intenso durante a ocupação principal. Adicionalmente, pacientes com AC apresentaram qualidade de vida e autoavaliação de saúde significativamente piores, comparativamente àqueles sem AC. CONCLUSÕES: Observou-se uma prevalência de 22% de algias vertebrais crônicas em um segmento da população da cidade de São Paulo. Fatores demográficos, socioeconômicos, psicológicos e físicos foram independentemente associados a essa condição. Observou-se também uma associação entre algias vertebrais crônicas e pior qualidade de vida / Introduction: Spinal pain is associated with significant economic and societal impact and is an important health issue. It has recently been listed as the first cause of -years lived with disability worldwide and one of the most common reasons for which people seek medical care. Estimates of lifetime prevalence of spinal pain vary between 54% and 80%. Objectives: To estimate the prevalence of chronic spinal pain (CSP) and to identify associated factors in a sample of persons aged 15 or older from a segment of the population of Sao Paulo City, Brazil. Methods: A cross-sectional epidemiologic survey was performed to determine the prevalence of chronic spinal pain and to identify associated factors in a random sample of persons 15 years or older from a segment of the population of São Paulo City, Brazil. Face-to-face interviews were performed with 826 individuals between December 2011 and February 2012. Participants responded the following instruments: Hospital Anxiety and Depression Scale, EuroQol 5D, Alcohol Use Disorders Identification Test (AUDIT), Fargerström Test for Nicotine Dependence (FTND), and Brazil Economic Classification Criteria (CCEB). Results: A prevalence of 22% (95% CI, 19.3 - 25.0) was observed for chronic spinal pain. The following factors were independently associated with chronic spinal pain: female gender, 30 years of age or older, four or less years of formal education, symptoms consistent with anxiety and intense physical strain for the main occupation. Quality of life and self-rated health were significantly worse among CSP individuals. Conclusions: This study found a prevalence of 22% for chronic spinal pain in a segment of the population of São Paulo city. Demographic, socioeconomic, psychological and physical factors were independently associated with this condition. Quality of life and self-rated health were significantly worse among CSP individuals

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-13T19:49:00Z No. of bitstreams: 1 lucianoambrosioferreira.pdf: 3321721 bytes, checksum: 8aa6e24d8b24fa74ffa52a7b23803d30 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-07-14T10:37:04Z (GMT) No. of bitstreams: 1 lucianoambrosioferreira.pdf: 3321721 bytes, checksum: 8aa6e24d8b24fa74ffa52a7b23803d30 (MD5) / Made available in DSpace on 2016-07-14T10:37:04Z (GMT). No. of bitstreams: 1 lucianoambrosioferreira.pdf: 3321721 bytes, checksum: 8aa6e24d8b24fa74ffa52a7b23803d30 (MD5) Previous issue date: 2011-03-25 / A desordem temporomandibular de sintomatologia crônica é acompanhada por uma diversidade de manifestações clínicas e emocionais que interagem de maneira desfavorável na percepção dolorosa dos pacientes. Considerando tal interação, o presente ensaio clínico propôs verificar a eficácia da terapia adjuvante de laser-acupuntura no controle sintomatológico destes pacientes através de uma avaliação duplo-cega controlada por placebo. O estudo foi conduzido em uma amostra de 40 indivíduos do gênero feminino, situados entre as idades de 20 e 40 anos, com diagnóstico de dor miofascial e artralgia crônicas, determinadas pelos Critérios de Diagnóstico para Pesquisas das Desordens Temporomandibulares (RDC/DTM). Os indivíduos foram aleatoriamente divididos em dois grupos: o experimental, que recebeu a terapia de laser-acupuntura adjuvante à intervenção oclusal por placa neuromiorrelaxante (PNMR); enquanto o grupo controle recebeu laser placebo associado à PNMR. Ambas as abordagens foram instituídas por um período de três meses, conduzidas por um mesmo terapeuta, cirurgião-dentista e acupunturista. A terapia de laser-acupuntura aconteceu uma vez por semana, por doze sessões e seguiu os seguintes parâmetros: radiação infravermelha com potência de 50mW, direcionada continuamente por 90 segundos aos pontos de acupuntura: ST6, SI19, GB20, GB43, LI4, LR3, TE3 e EX-HN3, definindo uma energia de 4,5J, uma densidade por ponto de 1250W/cm2 e uma densidade total de 112,5J/cm2. O desfecho principal incluiu a avaliação da evolução da sintomatologia física por meio da verificação mensal da intensidade da dor espontânea e da palpação muscular e articular, indicadas em uma escala visual analógica (EVA). Avaliou-se também a intensidade de sintomas de depressão e somatização por meio do RDC/DTM eixo II, aplicado antes e após a instituição terapêutica. Todas as avaliações foram conduzidas por um avaliador cego. Os resultados revelaram que a partir do primeiro mês das intervenções o grupo experimental exibiu valores de intensidade de dor expressivamente menores (p≤0,05) que o grupo controle, para todas as estruturas examinadas. Ao final das intervenções observou-se a remissão da sintomatologia dolorosa (EVA= 0) no grupo experimental e uma redução dos sintomas no grupo controle (EVA entre 2 e 4). Em relação aos aspectos psicossociais, os níveis de sintomas de somatização e depressão foram modificados com as intervenções 7 adotadas nos dois grupos, no entanto, o grupo experimental apresentou uma significativa diminuição frente ao grupo controle (p ≤ 0,05). A laser-acupuntura adjuvante à terapia oclusal reversível foi eficaz na remissão da sintomatologia física de desordem temporomandibular, além de atuar reduzindo os sintomas físicos inespecíficos e de depressão associados ao estresse e à dor crônica. / The temporomandibular chronic symptoms are accompanied by various clinical and emotional expressions that interact unfavorably on patients’ pain perception. Considering the statement, this clinical trial proposed to verify laser-acupuncture therapy efficacy to the patients’ symptoms through a double-blind evaluation controlled by placebo. The study was conducted on a sample of 40 female subjects, located between the ages of 20 and 40 years, with chronic myofascial pain and arthralgia diagnose, as determined by Research to Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Subjects were randomly divided into two groups: the experimental group that received the laser acupuncture therapy adjunct to reversible occlusal splint therapy (ROST), while the control group received placebo laser associated with ROST. Both approaches have been imposed for three months, driven by the same therapist, dentist and acupuncturist. Laser acupuncture therapy was applied once a week, for twelve sessions, defined by the parameters: infrared laser radiation, 50mW power output, directed punctuality for 90 seconds to acupuncture points: ST6, SI19, GB20, GB43, LI4, LR3, NT3 and EX-HN3, defining 4.5J energy, 1250W/cm2 density point and 112.5 J/cm2 total density. The primary outcome measure included an assessment of the physical symptoms evolution through the monthly check of the intensity of spontaneous and palpation pain, indicated on a visual analogue scale (VAS). The symptoms intensity of depression and somatization was evaluated by the RDC / TMD axis II, administered before and after therapy institution. All evaluations were conducted by a blind assessor. The result shows values of pain intensity significantly lower in experimental group (p ≤ 0.05) since the first month intervention for all structures examined. At the end of the interventions was observed remission of painful symptoms (VAS = 0) in the experimental group and a partial reduction of symptoms in the control group (VAS between 2 and 4). Regarding psychosocial factors, levels of somatization and depression symptoms were modified with the interventions taken in both groups, however, the experimental group showed a significant decrease (p ≤ 0,05) compared to the control group. The laser acupuncture as an adjunct therapy to reversible occlusal splint was effective in remission of temporomandibular disorder physics symptoms, also reducing nonspecific physical 9 symptoms and depression associated with stress and chronic pain.

Alzheimer’s disease (AD) is a neurodegenerative disease and the major cause of dementia, affecting more than 50 million people worldwide. Chronic pain is long-lasting, persistent pain that affects more than 1.5 billion of the world population. Overlapping and heterogenous symptoms of AD and chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. To characterize disease pathology of AD, we measured the protein changes in the temporal neocortex region of the brain of AD subjects using mass spectrometry (MS). We found proteins involved in exo-endocytic and extracellular vesicle functions displaying altered levels in the AD brain, potentially resulting in neuronal dysfunction and cell death in AD. To detect novel biomarkers for AD, we used MS to analyze cerebrospinal fluid (CSF) of AD patients and found decreased levels of eight proteins compared to controls, potentially indicating abnormal activity of complement system in AD. By integrating new proteomics markers with absolute levels of Aβ42, total tau (t-tau) and p-tau in CSF, we improved the prediction accuracy from 83% to 92% of early diagnosis of AD. We found increased levels of chitinase-3-like protein 1 (CH3L1) and decreased levels of neurosecretory protein VGF (VGF) in AD compared to controls. By exploring the CSF proteome of neuropathic pain patients before and after successful spinal cord stimulation (SCS) treatment, we found altered levels of twelve proteins, involved in neuroprotection, synaptic plasticity, nociceptive signaling and immune regulation. To detect biomarkers for diagnosing a chronic pain state known as fibromyalgia (FM), we analyzed the CSF of FM patients using MS. We found altered levels of four proteins, representing novel biomarkers for diagnosing FM. These proteins are involved in inflammatory mechanisms, energy metabolism and neuropeptide signaling. Finally, to facilitate fast and robust large-scale omics data handling, we developed an e-infrastructure. We demonstrated that the e-infrastructure provides high scalability, flexibility and it can be applied in virtually any fields including proteomics. This thesis demonstrates that proteomics is a promising approach for gaining deeper insight into mechanisms of nervous system disorders and find biomarkers for diagnosis of such diseases.

La douleur chronique est l’un des problèmes les plus complexes auxquels sont confrontées la médecine et les neurosciences. Au fil des siècles, il a été un casse-tête et reste encore un défi pour la recherche étant donné la complexité de sa nature. Parmi la quantité considérable de douleurs chroniques existantes, la douleur du membre fantôme est l’une de plus difficiles à traiter. Les études récentes montrent que les changements corticaux majeurs qui apparaissent après une amputation sont la conséquence de la douleur chronique fantôme. Je soutiens que la cause principale de la douleur fantôme est la non-acceptation de la perte d’une partie du corps, autrement dit, que la douleur mentale provoquée par la transformation de l’image de soi devient une douleur chronique physique, et que c’est l’esprit qui contrôle les réseaux cérébraux : bien qu’il émerge du cerveau, l’esprit arrive à le modifier du fait d’influences exogènes. L’analyse des études que j’ai réalisée pour tester mon hypothèse, m’a permis de constater que la perception douloureuse dépend de diverses influences externes qui sont indépendantes de l'entrée (signal) nociceptive. Je conclus que la plasticité corticale mise en évidence lors de l'expérience douloureuse chronique ne dépend pas seulement de l'action et de l'interaction entre les réseaux neuronaux dynamiques, mais aussi de la communication entre ces réseaux neuronaux (système endogène) et les réseaux environnementaux (système exogène), ces derniers étant capables de moduler la perception de la douleur. Je souligne donc l’importance de la reconnaissance du caractère mental de la douleur chronique et le besoin d’analyser sa dimension émotionnelle afin de la moduler. / Chronic pain is one of the most complex problems facing medicine and neuroscience. Over the centuries, it has been a puzzle and remains a research challenge given the complexity of its nature. Among the large number of existing different kinds of chronic pain, phantom limb pain is one of the most difficult to treat. Recent studies show that major cortical changes that appear after amputation are the result of chronic phantom limb pain. I argue that the main cause of phantom limb pain is the non-acceptance of the loss of a part of the body, that is to say, that the mental pain caused by the transformation of the self-image becomes a chronic physical pain. It is the mind that controls the cérébral networks : even if it emerges from the brain, the mind manages to modify it as a consequence of external influences. The analysis of the studies I performed to test my hypothesis, allowed me to confirm that the perception of pain depends on various external influences that are independent of the nociceptive signals. I conclude that the cortical plasticity highlighted during chronic painful experience does not only depend on the action and interaction between dynamic neural networks, but also on the communication between these neural networks (endogenous system) and environmental networks (exogenous system). These latter networks are capable of modulating the perception of pain. I therefore emphasize the importance of recognizing the mental nature of chronic pain and the need to analyze the emotional dimensions which modulate it.

No description available.

Contexte : La chronicité de la maladie est difficile, autant pour le soigné que pour le soignant. Malgré de nombreux travaux et recherches (réalisés principalement chez le soigné), la douleur chronique reste un fléau. Il est suggéré qu’une approche centrée sur la personne soit la meilleure pour aider ces patients. Il serait donc possible que la façon dont le médecin adapte sa clinique face au patient ait une influence. En regard de la douleur chronique, sa prise en charge difficile peut mener le soignant à ressentir de l’impuissance. Quelles stratégies utilise le soignant lorsque la pharmacopée est insuffisante ? S’il est répandu que les engagements spirituels des patients permettent d’attribuer un sens aux expériences de la douleur, peu de choses sont connues du côté des médecins. But : La présente étude explore les facteurs influençant la prise en charge par les médecins du patient douloureux chronique afin de comprendre comment leurs caractéristiques identitaires, spirituelles et relationnelles orientent leur approche de soins. Méthodes : Un dispositif de théorisation ancrée en recherche qualitative a été retenu. Le cadre conceptuel élaboré repose sur deux concepts clés : celui de l’identité narrative selon Ricœur et celui du temps selon Tillich. Les participants furent recrutés selon un échantillonnage de convenance. Des entrevues individuelles semi-structurées ont été conduites auprès de sept médecins de diverses spécialités, confrontés aux difficultés de prise en charge en contexte de douleur chronique. La moitié des participants ont été interviewés une seconde fois afin d’approfondir le thème de l’identité, et ce, jusqu’à saturation des données. Les transcriptions sont analysées selon la méthode de codification Strauss et Corbin. Résultats : Si le facteur temps était théoriquement connu de par la littérature sur la maladie douloureuse chronique, la collecte et l’analyse des données en a favorisé son émergence en tant que concept, révélant ainsi son importance implicite cruciale au sein de la relation thérapeutique. Notre approche, cadre à la fois théologique et inspirée de l’anthropologie philosophique, a permis d’identifier la reconnaissance en tant que processus émergent des données pour expliquer le cheminement de l’identité du médecin – professionnelle et personnelle – en contexte clinique de douleur chronique. Bien que non recherchée de façon explicite, la reconnaissance par le médecin (et indirectement par le douloureux chronique) apparaît comme source de motivation et d’énergie insoupçonnée afin d’entretenir une relation de qualité. La particularité du mot reconnaissance de se décliner en différents termes polysémiques a permis d’élaborer le processus de la re-connaissance vers la re-co-naissance mutuelle qui est ici proposé comme cadre explicatif de l’évolution de l’identité du médecin en contexte clinique relationnel de prise en charge du douloureux chronique. Le médecin doit ainsi se définir à nouveau en tant que thérapeute en vue de ne pas vivre l’échec. Conclusion : La compétence relationnelle acquise, ajoutée à sa compétence professionnelle, permet au médecin d’enrichir ses connaissances (savoir et expérience), mais aussi de cheminer, au fil du temps, avec son patient douloureux chronique, passant d’une re-connaissance (identitaire et spirituelle) à une re-co-Naissance mutuelle et dynamique dans la relation en contexte de douleur chronique. Les différentes perspectives pour les cliniciens et soignants s’occupant de ces patients sont discutées. / Abstract : Background: Chronic pain is difficult, both for the patient and the caregiver. Even though many studies and researches have been conducted (mostly with patients), chronic pain remains. It is suggested that a person-centered approach is the best way to help these patients. However, little is known about how physicians adapt their practice to their powerlessness when faced with chronic pain patient. Which strategies are to be used when the pharmacopoeia is insufficient? Though it is known that religious and spiritual commitments may allow patients to give meaning to their pain, little is known about how physicians deal with these commitments. Purpose: This study explores the factors influencing how physicians take charge of chronic pain patients to understand how their identity, their spirituality and their relationship shape their care approach. Methods: Within a qualitative research design in grounded theory, the conceptual framework developed is based on the two key concepts: the narrative identity by Ricœur and the concept of time by Tillich. Participants were recruited using a convenience sampling. Semi-structured individual interviews were conducted with seven physicians in various specialties dealing with the difficulties of chronic pain management. Four of them were interviewed a second time to further investigate the subjet, until data saturation. The transcripts were analyzed by Strauss and Corbin’s method of codification. Results: If the time factor was theoretically known from the literature on chronic pain, continuous and simultaneous data collecting and analyzing has brought its emergence as concept (axial coding), revealing thereby its implicit crucial importance within the therapeutic relationship. Our approach, inspired from both theological and philosophical anthropology‘s frames, have allowed us to identify “recognition” as an emerging process to explain the flow scheme of the physician’s professional and personal identity when faced with chronic pain. Although not researched explicitly, mutual recognition between patient and physician is a source of motivation to improve the quality of the relationship. The process of recognition to mutual re-co-birth (“re-co-naissance” in French) is proposed here as an explanatory framework for the development of the physician’s identity in the clinical context of chronic pain patient care. The French word “reconnaissance” (recognition) thus can be broken down into “re-co-naissance” (re-co-birth), the co-rebirth of a relationship to define oneself anew as a therapist and to not experience failure. Conclusions: The new acquired confidence and competence between physician and the patient, in addition to actual professional skills, enables the concerned physician not only to enrich his knowledge but also to make progress in time, along with his chronic pain patients, moving from professional identity to spiritual recognition and to a dynamic relationship of mutal re-birth and re-acknowledge (“re-co-naissance”), so that he no longer experiences medical failure. Various perspectives for clinicians and caregivers will be further discussed.

Background: Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Methods: Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. results: Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. conclusion: Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.

Background: Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Methods: Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. results: Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. conclusion: Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.