The profile of dexamethasone combined with transcranial direct current stimulation in rats submitted to an arthritis model / O perfil da dexametasona combinada com estimulação transcraniana por corrente contínua em ratos submetidos a um modelo de artrite

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund's adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: Para investigar métodos mais seguros e eficazes para o manejo da artrite reumatoide, avaliou-se o efeito do tratamento com dexametasona (DEX, 0,25mg/kg) combinado com estimulação transcraniana por corrente contínua (ETCC) sobre parâmetros comportamentais e bioquímicos de ratos submetidos a um modelo de artrite reumatoide. MÉTODOS: Trinta e seis ratos Wistar foram alocados em 4 grupos: controle+DEX (CTRL+DEX), artrite+DEX (AR+DEX), artrite+DEX+sham-ETCC (AR+DEX+sham-ETCC) e artrite+DEX+ETCC (AR+DEX+ETCC). O modelo de artrite foi induzido pela administração de complete Freund's adjuvant (CFA) na pata. Edema na pata e a alodínia mecânica foram avaliadas por pletismômetro e teste de von Frey, respectivamente. 14 dias após injeção de CFA, ratos foram tratados por 8 dias (DEX e/ou ETCC). Atividade locomotora foi avaliada pelo teste do campo aberto. TNF-alfa (hipocampo e medula espinal) e BDNF (córtex e tronco) foram mensurados por ELISA. RESULTADOS: Nas medições pré-tratamento, ratos com artrite exibiram aumento de o inchaço articular e alodínia mecânica comparados ao grupo controle, confirmando o estabelecimento de modelo de dor crônica. Também se observou discreto efeito antinociceptivo da dexametasona combinada com ETCC no modelo de artrite. O modelo de dor induziu um aumento no comportamento de grooming e reduziu os níveis de TNF-alfa no hipocampo; estes efeitos foram revertidos nos grupos sham- e ETCC ativo. Entretanto, não foram observados efeitos da DEX ou ETCC nos níveis de BDNF no córtex cerebral ou no tronco encefálico. CONCLUSÃO: Apesar dos discretos efeitos observados, não se pode descartar a ETCC como uma abordagem terapêutica não farmacológica para o manejo da dor crônica inflamatória na artrite reumatoide.

[Subcutaneous botulinum toxin in the treatment of peripheral neuropathic pain]. / Toxina botulínica subcutánea en el tratamiento del dolor neuropático periférico.

Neuropathic pain impairs quality of life in affected individuals and poses a challenge to clinicians due to the complexity of its treatment and frequent therapeutic failures. We present 4clinical cases of chronic neuropathic pain (LANSS ≥ 19), refractory to conservative treatment (meralgia paraesthetica, post-surgical pain and 2surgical scars). Subcutaneous botulinum toxin type A was infiltrated periodically over the painful area. All patients experienced subjective improvement in pain and improvement measured by the visual analogic scale. Pain relief started at 5-21 days and continued up to 1.5-3 months, and up to 9 months in one patient. Pain that reappeared was of lower intensity in 3patients and was reduced in area in 2patients.

Dolor En Síndrome De Guillain Barré: Una Manifestación Subestimada / Pain In Guillain Barré Syndrome: An Underestimated Manifestation

RESUMEN El Síndrome de Guillain-Barré es una polineuropatía desmielinizante aguda que se presenta clínicamente con debilidad muscular y trastornos autonómicos de forma típica, mientras que los síntomas sensitivos suelen pasar desapercibidos. Se describe la historia clínica de un paciente masculino con cuadriparesia fláccida aguda y trastornos sensitivos tipo parestesias y alodinia que dificultaron el diagnóstico durante su abordaje inicial. Luego del abordaje diagnóstico completo se confirmó la presencia del Síndrome de Guillain-Barré. Pese a que los síntomas sensitivos dificultaron el diagnóstico durante el ingreso, es importante destacar que el dolor es una manifestación frecuente de este trastorno, siendo subestimado en numerosos pacientes.

ABSTRACT Guillain-Barré syndrome is an acute demyelinating polyneuropathy that presents clinically with muscular weakness and autonomic disorders in its typical form, while the sensory symptoms usually go unnoticed. We describe the clinical history of a male patient with acute flaccid quadriparesis and sensory disorders such as paresthesia and allodynia that hinder diagnosis within the initial approach. Complete diagnostic work up confirmed the presence of Guillain-Barré syndrome. Although the sensory symptoms confused the diagnosis during admission, it is important to highlight that pain is a frequent manifestation of this disorder, being underestimated in many patients.

The potential role of neuropathic mechanisms in dry eye syndromes.

Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity.

Influência do comprimento de trabalho na dor pós-operatória após uma ou duas sessões de tratamento endodôntico: um ensaio clínico randomizado / Influence of working length on postoperative pain after single or twovisit endodontic treatment: a randomized clinical trial

O objetivo deste ensaio clínico foi avaliar a influência de dois comprimentos de trabalho foraminal diferentes na dor pós-operatória e alodinia mecânica após o tratamento endodôntico concluído em sessão única ou em duas sessões. Quarenta e oito pacientes adultos, indicados para tratamento endodôntico primário de dente com periodontite apical assintomática, foram randomizados em 4 grupos (n = 12): SV0 - tratamento em sessão única e instrumentação do canal radicular até o forame apical; SV+1 - tratamento em sessão única e instrumentação do canal radicular 1 mm além do forame apical; TV0 - tratamento em duas sessões e instrumentação do canal radicular até o forame apical; TV+1 - tratamento em duas sessões e instrumentação do canal radicular 1 mm além do forame apical. Todos os participantes receberam um questionário baseado em uma escala visual analógica para registrar sua avaliação da dor em 3 horas, 6 horas, 12 horas, 24 horas, 48 horas, 72 horas e 7 dias após o término do tratamento endodôntico. Para a avaliação mecânica da alodinia, a medição da força da mordida foi realizada utilizando um gnatodinanômetro digital imediatamente antes do tratamento e 7 dias após a sua conclusão. Não houve diferença estatisticamente significante entre os 4 grupos em relação a dor pós-operatória em todos os momentos avaliados (α = 5%, teste de Kruskal-Wallis). Os valores de força de mordida foram significativamente maiores 7 dias após o tratamento endodôntico, indicando que houve uma redução significativa da dor mecânica em todos os grupos, sem diferença significativa entre eles (α = 5%, ANOVA e teste de Tukey). Todos os grupos apresentaram a mesma taxa de dor pós-operatória nos momentos avaliados e efetivamente aumentaram os limiares mecânicos de dor(AU)

The objective of this clinical trial was to evaluate the influence of two different foraminal working lengths on postoperative pain and mechanical allodynia after endodontic treatment completed in single-visit or two-visit. Forty-eight adult patients indicated for primary endodontic treatment of tooth with asymptomatic apical periodontitis were randomly assigned to 4 groups (n = 12): SV0 ­ single-visit root canal treatment and instrumentation up to the apical foramen; SV+1 ­ single-visit root canal treatment and instrumentation 1 mm beyond the apical foramen; TV0 ­ twovisit root canal treatment and instrumentation up to the apical foramen; TV+1 ­ twovisit root canal treatment and instrumentation 1 mm beyond the apical foramen. All participants received a questionnaire based on a visual analog scale to record their assessment of pain at 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after the endodontic treatment concluded. For mechanical allodynia evaluation, bite force measurement was performed using a digital gnatodynanometer just before treatment and 7 days after its conclusion. No statistically significant difference was found among the 4 groups in relation to postoperative pain at all time points assessed (α= 5%, Kruskal-Wallis test). Bite force values were significantly higher 7 days after endodontic treatment, indicating that there was a significant reduction of mechanical pain in all groups, with no significant difference among them (α= 5%, ANOVA and Tukey?s test). All groups exhibited the same rate of postoperative pain at the time points assessed and effectively increased the mechanical pain thresholds(AU)

Síndrome regional complejo: revisión bibliográfica / Complex regional pain syndrome: a review

El síndrome de dolor regional complejo es una entidad clínica difícil de diagnosticar, especialmente cuando no se está familiarizado con el término. Para poder identificarlo es necesario conocerlo; produce un dolor espontáneo que cursa con hiperalgesia y alodinia como fenómenos distorsionados sensoriales, variaciones de flujo sanguíneo, sudoración y cambios tróficos por un estado inflamatorio localizado seguido por una etapa de desórdenes crónicos neuropáticos. Su presencia está relacionada más frecuentemente a un trauma inespecífico o un daño directo sobre una estructura nerviosa en las extremidades. Clásicamente es dividido en dos formas: Tipo I, anteriormente denominado Distrofia simpática refleja y el Tipo II, más conocido por el término de Causalgia. No ha sido posible establecer su fisiopatología, sin embargo se reconoce que se involucra todo el sistema nervioso para su instauración. Dentro de la práctica diaria del médico forense costarricense, se presenta la valoración de daño corporal en el ámbito laboral, penal y contencioso administrativo, por lo que es trascendental aprender a identificarlo, pues hay casos con factores en los cuales este síndrome puede ser planteado como secuela directa.

The complex regional pain syndrome is a clinical entity that is difficult to diagnose, especially when you are not familiar with the term. In order to identify it, it is necessary to know it well. It produces spontaneous pain like hyperalgesia and allodinya causing sensory distorted phenomena, variations of blood flow, sweating, and trophic changes by a localized inflammatory condition, followed by a stage of chronic neuropathic disorders. Its presence is most often related to an unspecified trauma or direct damage to a nerve structure in the extremities. Generally, it is divided in two forms: type I, formerly known as reflex sympathethic dystrophy, and type II, better known as causalgia. Though it has not been possible to establish its pathophysiology, it is recognized that the entire nervous system is involved. In daily practice, a Costa Rican forensic doctor is presented with the assessment of bodily harm in the fields of work accidents, criminal agressions, and administrative litigation. Since there are cases in which this syndrome may be directly related, it is extremely important to learn how to identify it successfully.

12 item Allodynia Symptom Checklist/Brasil: cross-cultural adaptation, internal consistency and reproducibility / 12 item Allodynia Symptom Checklist/Brasil: adaptação transcultural, consistência interna e reprodutibilidade

Since there was no Portuguese questionnaire to evaluate cutaneous allodynia, which has been pointed out as a risk factor of migraine, we aimed to perform the cross-cultural adaptation of the 12 item Allodynia Symptom Checklist for the Brazilian population and to test its measurement properties. It consisted in six stages: translation, synthesis, back translation, revision by a specialist committee, pretest and submission the documents to the committee. In the pretest stage, the questionnaire was applied to 30 migraineurs of both sexes, who had some difficulty in understanding it. Thus, a second version was applied to 30 additional subjects, with no difficulties being reported. The mean filling out time was 3'36", and the internal consistency was 0.76. To test reproducibility, 15 other subjects filled out the questionnaire at two different times, it was classified as moderate (weighted kappa=0.58). We made available to Brazilian population an easy, quick and reliable questionnaire.

Levando em consideração que não há nenhum questionário em português disponível para avaliação da alodinia cutânea, sintoma que tem sido apontado como fator de cronificação da migrânea, o objetivo do trabalho foi realizar a adaptação transcultural do 12 item Allodynia Symptom Checklist para a população brasileira e testar suas características psicométricas. A adaptação foi realizada em seis estágios: tradução, síntese, retrotradução, revisão pelo comitê de especialistas, pré-teste e submissão dos documentos ao comitê. No estágio do pré-teste, foram aplicados 30 questionários em migranosos de ambos os sexos, que relataram dificuldades de compreensão. Por isso, foi criada uma segunda versão e aplicada a mais 30 sujeitos, não tendo sido relatadas dificuldades nesta versão. O tempo médio de preenchimento foi de 3'36", e a consistência interna encontrada foi 0,76. Para testar a reprodutibilidade, outros 15 sujeitos preencheram o questionário, em dois momentos, tendo sido a reprodutibilidade classificada como moderada (kappa ponderado=0,58). Portanto, disponibilizamos, para uso na população brasileira, um questionário fácil, rápido e confiável.

Interference of age and repetition of the same noxious stimulus on hyperalgesia / Interferência da idade e repetição do mesmo estímulo doloroso na hiperalgesia

Pain in animals has been recognized for less than one century. Several authors confirm that animals are capable to process, register and modulate nociceptive stimuli in a very similar way to human kind and there are several evidences registering the impact of pain sensation over vital systems interfering on disease outcome. Nevertheless, despite some evidences that animals, as human beings, can store information from past painful experiences less is known about how this so called pain memory works. The aims of this study were: to evaluate if the response to a painful stimuli differs during different stages of life and if repetition of a same acute stimuli in the same animal interferes with expression of hyperalgesia. Thus, 60 rats were selected and arranged in 3 equal groups: 3 months, 6 months, and 9 months of age. All animals were injected 5 percent formalin solution in the plantar face of hind paw under volatile general anesthesia. Von Frey filaments were applied at 1h, 24h and 48h after sensitization. Injection was repeated twice with a 30-day interval, each time in a different hind paw. Results showed that younger rats express lower hyperalgesia thresholds in the first stimulation compared to elder animals and that repetition of same stimulus diminishes hyperalgesia thresholds when it begins during infant period and augments hyperalgesia thresholds when it begins during elder ages.

A dor nos animais tem sido reconhecida há pouco manos de um século. Vários autores reconhecem que os animais são capazes de processar, registrar e modular estímulos nociceptivos de modo muito similar aos seres humanos e há várias evidências registrando o impacto da sensação dolorosa sobre os sistemas vitais e curso da doença. Entretanto, a despeito das evidências de que os animais, como os seres humanos, podem armazenar informações passadas de experiências dolorosas pouco se sabe sobre como a chamada memoria de dor funciona. Os objetivos deste estudo foram: avaliar se a resposta a um estímulo doloroso difere em diferentes fases da vida e se a repetição de um mesmo estímulo doloroso agudo no mesmo animal interfere na expressão da hiperalgesia. Assim, 60 ratos foram selecionados e agrupados em três grupos iguais: 3 meses, 6 meses e 9 meses. Foi injetada solução de formalina 5 por cento na face plantar de todos os animais durante anestesia. O limiar de hiperalgesia foi testado pelo método de filamentos de Von Frey à 1h, 24h e 48h após a sensibilização. A injecão foi repetida duas vezes com intervalo de 30 dias, uma vez em cada membro. Os resultados demonstraram que animais mais jovens possuem limiares menores de hiperalgesia na primeira estimulação, comparados com os mais velhos e que a repetição de um mesmo estímulo doloroso agudo diminui o limiar de hiperalgesia quando o primeiro estímulo ocorre nas idades mais tenras e aumenta o limiar quando se inicia em idades mais avançadas.

Neuroplasticidad y dolor / Neuroplasticity and pain

Todas las formas de dolor incluyen el desarrollo de un estado de hiperalgesia que ilustra la naturaleza dinámica y plástica de la sensación de dolor. La hiperalgesia es la característica más importante del proceso doloroso y es la expresión de la hipersensibilidad de las vías del dolor inducida por la sensibilización de los receptores periféricos que registran eventos dolorosos y de las neuronas que transmiten y procesan esta información sensorial al SNC. Los nociceptores periféricos se sensibilizan adquiriendo una mayor y a veces nueva capacidad de respuesta a los estímulos periféricos. Por otra parte, un proceso de plasticidad sináptica, del cual se ha identificado una variedad de componentes moleculares, interviene en la amplificación central de las señales de las aferencias nociceptivas, lo cual evoca la hipersensibilidad de las neuronas centrales. El resultado final es un proceso sensorial que, a pesar de haber sido puesto en marcha inicialmente por una lesión, puede no mantener una relación estrecha con la lesión original y convertirse en un estado de dolor crónico sin tener una causa definida.

All froms of pain include the development of a hyperalgesic state that illustrates the dynamic and plastic nature of pain sesation. Hyperalgesia is the most prominent feature of the pain process and is the expression of hypersensitivity of the pain pathway induced by the sensitization of the peripheral receptors that signal painful events and of the neurons that transmit and process this sensory information to the CNS. Peripheral nociceptors can be sensitized, acquiring enhanced, and sometimes novel, responsiveness to peripheral stimuli. On the other hand a process of synaptic plasticity, of which several molecular components have already been identified, mediates the central amplification of the afferent signals that leads to the hypersensitivity of central neurons. The final result is a sensory process that, although initially triggered by injury, may not keep a close relationship with the originating injury and develop into a chronic pain state in the absence of a defined cause.

Dolor en el trauma térmico / Pain in thermal trauma

La máxima agresión física que puede sufrir un ser humano son las quemaduras. Actualmente, en Chile se hospitalizan alrededor de 9.000 personas al año por quemaduras, con una tasa de mortalidad que ha ido en disminución en los últimos 20 años, por lo tanto la cantidad de pacientes sobrevivientes va en aumento. La IASP (Internacional Association for Study of Pain) definió el dolor en quemados como: "un dolor agudo y grave, que se produce al sufrir una quemadura y luego continuo con exacerbaciones que declinan gradualmente". El dolor en el trauma térmico está siempre presente, es de intensidad severa y prolongada en el tiempo, con una alta prevalencia de dolor crónico. Se sabe que el aumento en la intensidad se debe a que las quemaduras dañan gran cantidad de nociceptores, produciéndose una amplificación de la respuesta al dolor. Los opioides son el principal pilar en el tratamiento farmacológico. Es fundamental el buen manejo del dolor, para evitar el dolor patológico que aumentará el dolor crónico y con ello el desmedro de la vida personal de nuestros pacientes. Desafortunadamente el subtratamiento es una realidad, produciendo directamente un retraso en la recuperación de sus quemaduras y en la inserción social y laboral.

Burns are the greatest physical aggression that a human being can experience. In Chile, approximately 9000 patients are hospitalized annually due to burns, with a mortality rate that has decreased progressively in the last 20 years, which means that the amount of survivors is increasing. The IASP (International Association for Study of Pain) has defined pain in the burn patient as "an acute and severe pain produced by a burn that later continues with exacerbations that gradually decline". Pain in thermal trauna is always present, of severe intensity and prolonged in time, with a high prevalence of chronic pain. It is Known that the increase in intensity of pain is due to the damage of a great number of nociceptors, that produces an amplification of the response to pain. Opioids are the mainstay of pharmacologic treatment. Appropriate management of pain is fundamental to avoid pathologic pain that will increase the chronic pain and deteriorate the quality of life of our patients. Unfortunately undertreatment is a reality, retarding the healing of the burn wound, and the social and workplace reintegration.