Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury

PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.

El Profesor Doctor Hernán Alessandri Rodríguez (1900-1980) / Professor Hernán Alessandri, M.D. (1900-1980)

Hernán Alessandri M.D. was an astounding clinician and a leading medical educator, born in Santiago in 1900 where he died in 1980. He received his medical degree at the University of Chile in 1923, became Professor of Clinical Medicine in 1932, Full Professor and Chair of Internal Medicine in 1944. At the Hospital del Salvador, in Santiago, he chaired a teaching Department and a Clinical Service that was an example for its academic environment and dedication to patients and students. From 1958 to 1962 he was Dean of the University of Chile Faculty of Medicine, conducting a reform of teaching curricula and organizing medical residency programs for the training of specialists, originally started in his own Service in 1952. The American College of Physicians awarded him the first foreign Honorary Membership. He was a founding Member of the Chilean Academy of Medicine (1964). In 1973 the University of Chile awarded him the Emeritus Professor status. He was considered by his peers, alumni and patients a brilliant clinician and an exceptional medical educator. Since 1980 a Social and Teaching Foundation bears his name and in 2014, with the occasion of the XXXV Chilean Congress of Internal Medicine, the Sociedad Médica de Santiago-Chilean Society of Internal Medicine created an annual lecture to render tribute to distinguished physicians and his name was one of the two selected to inaugurate them.

TWIK-Related Spinal Cord K+ Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation

PURPOSE: The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.

Limits and possibilities experienced by nurses in the treatment of women with chronic venous ulcers / Límites y posibilidades vividas por enfermeras en el tratamiento de mujeres con úlcera venosa crónica / Limites e possibilidades vivenciados por enfermeiras no tratamento de mulheres com úlcera venosa crônica

Objective To understand the experiences and expectations of nurses in the treatment of women with chronic venous ulcers. Method Phenomenological research was based on Alfred Schütz, whose statements were obtained in January, 2012, through semi-structured interviews with seven nurses. Results The nurse reveals the difficulties presented by the woman in performing self-care, the perceived limitations in the treatment anchored in motivation, and the values and beliefs of women. It showed professional frustration because venous leg ulcer recurrence, lack of inputs, interdisciplinary work and training of nursing staff. There was an expected adherence to the treatment of women, and it emphasized the need for ongoing care, supported self-care and standard practices in treatment. Conclusion That treatment of chronic venous leg ulcers constitutes a challenge that requires collective investment, involving women, professionals, managers and health institutions. .

Objetivo Comprender las experiencias y expectativas de enfermeras en el tratamiento de mujeres con úlcera venosa crónica. Método Investigación fenomenológica fundamentada en Alfred Schutz, que buscó Se realizó entrevista semiestructurada con siete enfermeras, en enero del 2012. Resultados La enfermera revela dificultades presentadas por la mujer para realizar el autocuidado, percibe limitaciones en el tratamiento relacionadas con la desmotivación, los valores y las creencias de las mujeres. Refiere frustración profesional debido a la recidiva de la lesión, a la falta de insumos, al deficiente trabajo interdisciplinar y a la limitada capacitación del equipo de enfermeras. Espera la adhesión de la mujer al tratamiento y resalta la necesidad del cuidado continuo, del autocuidado apoyado y de estandarizar conductas de tratamiento. Conclusión El tratamiento de la úlcera venosa crónica es un desafío que requiere contribución colectiva, involucrando a las mujeres, a los profesionales, a los gestores y a las instituciones de salud. .

Objetivo Compreender as experiências e expectativas de enfermeiras no tratamento de mulheres com úlcera venosa crônica na Atenção Primária à Saúde. Método Pesquisa fundamentada na fenomenologia social de Alfred Schütz, com depoimentos obtidos em janeiro de 2012, por meio de entrevista semiestruturada com sete enfermeiras. Resultados As enfermeiras revelam dificuldades apresentadas pelas mulheres com úlcera venosa crônica para realizar o autocuidado, percebem limitações na terapêutica ancoradas na desmotivação e nos valores e crenças das mulheres. Referem frustração profissional em razão da recidiva da lesão, falta de insumos e tecnologia, de trabalho interdisciplinar e da capacitação da equipe de enfermagem. Esperam a adesão das mulheres ao tratamento e ressaltam a necessidade do cuidado contínuo, do autocuidado apoiado e da padronização de condutas no tratamento. Conclusão O tratamento da úlcera venosa crônica constitui-se em um desafio que requer investimento coletivo, envolvendo a mulher, os profissionais, os gestores e as instituições de saúde. .

Midazolam oral como medicação pré-anestésica em blefaroplastias / Oral sedation with midazolam in blepharoplasty

OBJETIVO: Avaliar a eficácia e a segurança do emprego oral de midazolam (15 mg) como medicação pré-anestésica em pacientes submetidos a blefaroplastias. MÉTODOS: Foi desenvolvido um ensaio clínico prospectivo, duplo cego, randomizado, controlado com 42 pacientes, risco ASA I e II, divididos em três grupos de 14 pacientes: grupo M (midazolam 15 mg), grupo P (placebo) e grupo SM (sem medicação). Os pacientes foram avaliados quanto ao grau de sedação e dor intraoperatórias e variação entre os períodos pré e transoperatórios da ansiedade, pressão arterial sistólica e diastólica, frequência respiratória e pulso. RESULTADOS: A análise de variância unifatorial com teste de Tukey mostrou que a administração de midazolam ocasionou uma redução significativa da pressão arterial sistólica e da frequência respiratória no período transoperatório em relação aos pacientes que utilizaram placebo ou não fizeram uso de medicamento. Esses efeitos foram discretos e acompanhados de diminuição na percepção da dor, discreta sedação e redução da ansiedade. CONCLUSÃO: A sedação via oral com midazolam em pacientes submetidos a cirurgias palpebrais demonstrou ser eficiente de fácil aplicação e com mínimos efeitos sistêmicos.

PURPOSE: To evaluate the safety and usefulness of the use of oral sedation with midazolam (15 mg) in patients submitted to blepharoplasty. METHODS: Randomized double-blind prospective study of 42 patients (surgical risk ASA I and II) divided into three groups of 14 patients each: Group M (midazolam 15 mg), group P (placebo) and group SM (no medication). All patients were evaluated according to the degree of sedation and pain during surgery and the variation of anxiety between the preoperative and intraoperative period, arterial pressure (systolic-SAP and diastolic-DAP), respiratory frequency (RF) and pulsation. RESULTS: Unifatorial variance analysis with Tukey test demonstrated that the use of midazolam provoked a significant SAP and RF reduction during the intraoperative period. These effects were not pronounced and were accompanied by a reduction of pain perception and anxiety and mild sedation. CONCLUSIONS: Oral sedation with midazolam in patients that had undergone eyelid surgical procedures is safe and easy to perform with minimal systemic effects.

Parte I: dolor en niño / Pain in children: part I

La intención de este capítulo es mostrar las particularidades que el niño presenta frente al dolor: lo perjudicial que puede ser para la evolución de la enfermedad o la recuperación de un procedimiento, y que aún cuando hay muchas cosas que no sabemos, con lo que se conoce y se cuenta, debiera hacerse más que lo habitualmente se ve en una práctica clínica.

Studies on the changes of c-fos protein in spinal cord and neurotransmitter in dorsal root ganglion of the rat with an experimental peripheral neuropathy

Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.

Aproximación psicológica del dolor postoperatorio / Psychological approaching of postoperatory pain

El dolor es un fenómeno complejo, multidimensional, que no resulta suceptible de ser entendido por explicaciones simplistas de corte biológico o psicológico. Las dimensiones del dolor no pueden considerarse de forma aislada, sino una en función de las otras, tanto es así que con frecuencia la alteración emocional cierra un cículo vicioso con la intensidad del dolor persibido. También existe una estrecha relación entre el dolor percibido y la recuperación postoperatoria. Se hace viable por lo tanto, la utilización de métodos psicológicos, no sólo para el diagnóstico sino también para complementar el tratamiento del dolor; existen algunos que han demostrado ser lo suficientemente objetivos, confiables y válidos para ser incluidos dentro de los programas ideados a este fin dentro del marco hospitalario