Triple primario oncológico y su impacto en el dolor. Reporte de caso / Triple primary malignancy and its impact on pain. A case report

Introducción: Los pacientes con cáncer presentan dolor en un 40% y el 38% de ellos lo califica como moderado a intenso. Casi el 85% de los pacientes con dolor por cáncer pueden lograr un buen control con medicamentos orales convencionales. Caso clínico: masculino de 57 años con triple neoplasia maligna primaria metacrónica asociada a tres tipos de dolor con incremento progresivo de la intensidad y requerimiento de varias líneas de tratamiento analgésico opioide. Conclusión: Las neoplasias malignas primarias triples son infrecuentes y están asociadas a dolor complejo, siendo los opioides la opción terapéutica más adecuada.

Introduction: Pain is an unpleasant sensory and emotional experience associated with real or potential tissue damage, which treatment is more difficult in patients with multiple and advanced cancer, influencing their functionality, mood, sleep, and quality of life. Clinical case: 57-year-old male with metachronous triple primary malignancy associated with three types of pain with a progressive increase in intensity and requiring several lines of opioid analgesic treatment. Conclusion: Triple primary malignancies are uncommon and primarily associated with complex pain; opioids are the most appropriate therapeutic option.

Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

ABSTRACT O sistema opioidérgico envolve a regulação do sono e da vigília. É possível, portanto, que os polimorfismos genéticos no OPRM1 influenciem na qualidade do sono. Este estudo investigou a associação de polimorfismos do OPRM1 com a qualidade subjetiva do sono entre indivíduos sem tratamento prévio com opióides. Este estudo observacional de corte transversal envolveu 161 homens que nunca haviam se tornado opióides (média de idade = 27,74 anos; variação: 18 a 63 anos). A qualidade subjetiva do sono foi avaliada com a versão traduzida e validada em malaio do Índice de Qualidade do Sono de Pittsburgh (PSQI). O DNA foi extraído do sangue total e submetido à reação em cadeia da polimerase (PCR) para dois polimorfismos OPRM1 (118A> G e IVS2 + 691G> C). Sujeitos combinados com 118A e IVS2 + 691Galelos (haplótipo AC) apresentaram escores significativamente mais baixos do PSQI [média (DP) = 4,29 (1,76)] em comparação àqueles sem o haplótipo [4,99 (2,50)] (p = 0,004). Por outro lado, os indivíduos com genótipo heterozigótico combinado (GC / AG diplotipo) apresentaram escores significativamente mais altos do PSQI em comparação àqueles sem o diplótipo [6,04 (2,48) vs 4,54 (2,22), p = 0,004]. Em indivíduos sem tratamento prévio com opiáceos, o haplótipo AC e o diplótipo GC / AG para os polimorfismos 118A> G e IVS2 + 691G> C do OPRM1 estão associados a uma melhor e pior qualidade do sono, respectivamente.

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats / O efeito analgésico de tramadol não é mediado por receptores opioides na dor de ratos no pós-operatório imediato / El efecto analgésico del tramadol no está mediado por receptores opiáceos en el dolor en ratones en el postoperatorio inmediato

BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. .

JUSTIFICATIVA E OBJETIVOS: Tramadol é conhecido como um fármaco analgésico de ação central, usado para o tratamento de dor moderada a grave. O efeito analgésico local foi demonstrado, em parte devido ao efeito semelhante ao anestésico local, mas outros mecanismos permanecem obscuros. O papel dos receptores opioides periféricos no efeito analgésico local não é conhecido. Neste estudo, examinamos o papel dos receptores opioides periféricos no efeito analgésico local de tramadol em modelo de incisão plantar. MÉTODOS: Ratos Wistar, jovens e machos, foram divididos em sete grupos: controle, tramadol intraplantar, tramadol intravenoso, tramadol intraplantar-naloxona intravenosa, tramadol intraplantar-naloxona intraplantar, tramadol intravenoso-naloxona intravenosa e naloxona intravenosa. Após receber os medicamentos designados (5 mg de tramadol, 200 mg de naloxona ou NaCl a 0,9%, os ratos foram submetidos à incisão plantar e os limiares de retirada após estímulos mecânicos com filamentos de von Frey foram avaliados no início do estudo e nos minutos 10, 15, 30, 45 e 60 após a incisão. RESULTADOS: A incisão plantar levou à hiperalgesia mecânica acentuada durante todo o período de observação no grupo controle; hiperalgesia mecânica não foi observada nos grupos tramadol intraplantar, tramadol intraplantar-naloxona intraplantar e tramadol intraplantar-naloxona intravenosa. No grupo tramadol intravenoso, um aumento tardio do limiar de retirada (após 45 minutos) foi observado. Os grupos tramadol intravenoso-naloxona intravenosa e naloxona intravenosa permaneceram hiperalgésicos durante todo o período. CONCLUSÕES: Tramadol apresentou efeito analgésico local inicial e diminuiu a hiperalgesia mecânica induzida pela incisão plantar. Esse efeito analgésico não foi mediado por receptores opioides periféricos. .

JUSTIFICACIÓN Y OBJETIVOS: Al tramadol se le conoce como un medicamento analgésico de acción central usado para el tratamiento del dolor moderado a intenso. El efecto analgésico local quedó demostrado, en parte, a causa del efecto similar al del anestésico local, pero otros mecanismos permanecen sin clarificar. El rol de los receptores opiáceos periféricos en el efecto analgésico local no se conoce. En este estudio, examinamos el papel de los receptores opiáceos periféricos en el efecto analgésico local del tramadol en un modelo de incisión plantar. MÉTODOS: Ratones Wistar, jóvenes y machos, fueron divididos en 7 grupos: control, tramadol intraplantar, tramadol intravenoso, tramadol intraplantar-naloxona intravenosa, tramadol intraplantar-naloxona intraplantar, tramadol intravenoso-naloxona intravenosa, y naloxona intravenosa. Después de recibir los medicamentos designados (5 mg de tramadol, 200 µg de naloxona o NaCl al 0,9%), los ratones fueron sometidos a la incisión plantar, y los umbrales de retirada de la pata posteriores a los estímulos mecánicos con filamentos de von Frey fueron evaluados al inicio del estudio y en los minutos 10, 15, 30, 45 y 60 después de la incisión. RESULTADOS: La incisión plantar conllevó hiperalgesia mecánica acentuada durante todo el período de observación en el grupo control; la hiperalgesia mecánica no fue observada en los grupos tramadol intraplantar, tramadol intraplantar-naloxona intraplantar, y tramadol intraplantar-naloxona intravenosa. En el grupo tramadol intravenoso, fue observado un aumento tardío del umbral de retirada (después de 45 min); los grupos tramadol intravenoso-naloxona intravenosa y naloxona intravenosa permanecieron hiperalgésicos durante todo el período. CONCLUSIONES: El tramadol presentó un efecto analgésico local inicial, disminuyendo la hiperalgesia mecánica inducida por la incisión plantar. Ese efecto analgésico no fue mediado por receptores opiáceos periféricos. .

Expressions of matrix metalloproteinases-1 and -9 and opioid growth factor in rabbit cornea after lamellar keratectomy and treatment with 1% nalbuphine / Metaloproteinases de matriz 1, 9, e fator de crescimento opióide, em córneas de coelhos depois de ceratotomia e tratamento com nalbufina a 1%

ABSTRACT Purposes: To evaluate the effects of nalbuphine 1% on the expression of metalloproteinase 1 (MMP-1), metalloproteinase 9 (MMP-9), and opioid growth factor (OGF) in rabbit corneas after lamellar keratectomy. Methods: The rabbits were assigned to two groups: group nalbuphine (GN, n=30), which received 30 µL of nalbuphine 1% in 4 daily applications at regular intervals until corneal epithelialization, and group control (GC, n=30), which received physiological saline solution under the same conditions adopted in GN. The corneas were collected for immunohistochemistry on days 1, 3, 5, 7, and 9 after lamellar keratectomy, and the expressions of MMP-1, MMP-9, and OGF were analyzed. Results: The expressions of MMP-1 and MMP-9 increased until day 5 of the evaluation, with no differences observed between GN and GC (p>0.05). On days 7 and 9, significant reductions were observed in the expression of MMP-1 (p<0.01), with no differences observed between GN and GC (p>0.05). The expression of OGF was constant in all periods (p>0.05), restricted to the corneal epithelium, and there was no difference between the groups (p>0.05). Conclusions: The study results showed that nalbuphine 1% did not alter the expression patterns of MMP-1, MMP-9, and OGF in rabbit corneas after lamellar keratectomy. .

RESUMO Objetivos: Avaliar os efeitos da nalbufina 1% sobre a expressão da metaloproteinase 1 (MMP-1), da metaloproteinase 9 (MMP-9) e do fator de crescimento opióide (OGF), em córneas de coelhos submetidas à ceratectomia lamelar. Métodos: Constituíram-se dois grupos: grupo nalbufina (GN, n=30), que recebeu 30 µL de nalbufina 1% em 4 aplicações diárias, a intervalos regulares, até a epitelização corneal; controle (GC, n=30), que recebeu solução salina nas mesmas condições adotadas no GN. As córneas foram colhidas para imuno-histoquímica decorridos 1, 3, 5, 7 e 9 dias das ceratectomias lamelares, visando a se avaliarem as MMP-1, MMP-9 e OGF. Resultados: A expressão das MMP-1 e de MMP-9 se elevou até o quinto dia de avaliação, sem diferença entre GN e GC (p>0,05). Nos dias 7 e 9, observou-se redução significativa na expressão das enzimas (p<0,01), sendo que diferenças não foram observadas entre os grupos (p>0,05). O OGF exibiu imunomarcação constante em todos os períodos (p>0,05), restrita ao epitélio corneal. Não foram encontradas diferenças entre os grupos (p>0,05). Conclusões: Com base dos resultados obtidos, há como admitir que a nalbufina 1% não alterou o padrão de expressão da MMP-1, da MMP-9 e do OGF em córneas de coelhos submetidas à ceratectomia lamelar. .

Effect of prosthodontic planning on lateral occlusion scheme: a comparison between conventional and digital planning

Recently, digital wax-up is proposed as a tool to aid prosthodontic planning. However, there are no data about the effect of prosthodontic planning on lateral occlusion scheme. Objective : This study aims to evaluate the impact of conventional and digital prosthodontic planning on lateral occlusion scheme. Material and Methods : Dental models of 10 patients were collected. All models had Angle Class I occlusion and were undergoing prosthodontic treatment that would influence the lateral occlusion scheme. Each set of models had received both conventional wax-up and digital wax-up. In relation to the lateral occlusion scheme, the following variables were evaluated: the prevalence of the different lateral occlusion scheme, number of contacting teeth and percentage of each contacting tooth. Four excursive positions on the working side were included: 0.5, 1.0, 2.0 and 3.0 mm from the maximal intercuspation position. Results : The lateral occlusion scheme of the two wax-up models was subjected to alterations following excursion. There was a tendency for the prevalence of canine-guided occlusion to increase and for the prevalence of group function occlusion to decrease with increasing excursion. The number of contacting teeth was decreasing with the increasing magnitude of excursion. For the 0.5 mm and 1.0 mm positions, the two wax-ups had significantly greater contacts than the pre-treatment models, while at the 2.0 mm and 3.0 mm positions, all the models were similar. For all models, canines were the most commonly contacting teeth, followed by the teeth adjacent to them. No difference was observed between the two wax-ups in relation to the number of contacting teeth. Conclusion : Although the prosthodontic planning had influenced the pattern of the lateral occlusion scheme and contacts, there was no difference between the conventional and digital prosthodontic planning. .

Metabolic effects of exercise on childhood obesity: a current view / Efeitos metabólicos do exercício físico na obesidade infantil: uma visão atual

OBJECTIVE: To review the current literature concerning the effects of physical exercise on several metabolic variables related to childhood obesity. DATA SOURCE: A search was performed in Pubmed/MEDLINE and Web of Science databases. The keywords used were as follows: Obesity, Children Obesity, Childhood Obesity, Exercise and Physical Activity. The online search was based on studies published in English, from April 2010 to December 2013. DATA SYNTHESIS: Search queries returned 88,393 studies based on the aforementioned keywords; 4,561 studies were selected by crossing chosen keywords. After applying inclusion criteria, four studies were selected from 182 eligible titles. Most studies found that aerobic and resistance training improves body composition, lipid profile and metabolic and inflammatory status of obese children and adolescents; however, the magnitude of these effects is associated with the type, intensity and duration of practice. CONCLUSIONS: Regardless of the type, physical exercise promotes positive adaptations to childhood obesity, mainly acting to restore cellular and cardiovascular homeostasis, to improve body composition, and to activate metabolism; therefore, physical exercise acts as a co-factor in fighting obesity. .

OBJETIVO: Revisar a literatura atual a respeito dos efeitos do exercício físico sobre diferentes variáveis metabólicas da obesidade infantil. FONTES DE DADOS: A pesquisa foi feita nas bases de dados Pubmed e Web of Science. Os descritores usados foram: obesity, children obesity, childhood obesity, exercise e physical activity. A pesquisa eletrônica foi feita com base nos estudos publicados de abril de 2010 a dezembro de 2013, em idioma inglês. SÍNTESE DOS DADOS: O rastreamento dos estudos com os descritores encontrou 88.393. Após cruzamento entre os descritores, obtiveram-se 4.561. Desses, depois da análise dos títulos, foram cogitados 182 relevantes referências, submetidos então aos critérios de inclusão/exclusão, e totalizaram, no fim, 39. A maioria dos estudos relacionou a prática de exercícios físicos aeróbicos e resistidos à melhoria da composição corporal, à regulação do perfil lipídico e metabólico e ao estado inflamatório de crianças e adolescentes obesos. Entretanto, a magnitude dos efeitos está associada ao tipo, à intensidade e à duração da prática. CONCLUSÕES: O exercício físico, independentemente do tipo, mostra-se capaz de promover adaptações positivas sobre a obesidade infantil, principalmente por atuar na restauração da homeostase celular e sistema cardiovascular, na melhoria da composição corporal e também aumento da ativação metabólica. .

Efeito analgésico periférico do tramadol em modelo de dor pós-operatória em ratos / Peripheral analgesic effect of tramadol in a postoperative pain model in rats

INTRODUÇÃO: Tramadol é conhecido como um fármaco analgésico de ação central utilizado no tratamento de dores de intensidades moderada a forte. Efeito analgésico local já foi demonstrado. É, em parte, semelhante ao efeito anestésico local, mas outros mecanismos permanecem desconhecidos. O papel de receptores opioides periféricos na analgesia do tramadol na dor pós-operatória não é conhecido. Neste estudo, foi estudado o papel dos receptores opioides no efeito analgésico local do tramadol em modelo de dor por incisão plantar. MÉTODOS: Ratos machos jovens foram submetidos à incisão plantar e no primeiro dia pós-incisão foram divididos em quatro grupos: Grupo IP I-SF/SF - 50 uL de solução de NaCl 0,9% foram injetados na região plantar da pata posterior homolateral à incisão e, 15 minutos depois, novamente injetada a mesma quantidade de solução; Grupo IP II-SF/T_homo - 50 uL de NaCl 0,9% foram injetados na região plantar da pata homolateral e, 15 minutos depois, injetados 50 µL solução contendo 5 mg tramadol; Grupo IP III-SF/T_contra -50 uL de NaCl 0,9% foram injetados na região plantar da pata contralateral e, 15 minutos depois, 50 uL de solução contendo 5 mg de tramadol; Grupo IP IV-Nal/T_homo - 50 uL de solução contendo 200 ug de naloxona foram injetados na pata homolateral e, 15 minutos depois, 50 uL de solução contendo 5mg de tramadol foi injetada. Antes de receberem as injeções, os limiares de retirada da pata por estímulo mecânico produzido por analgesímetro eletrônico de von Frey foram medidos, e, depois da administração dos fármacos, os limiares de retirada foram avaliados nos tempos 15, 30, 45 e 60 minutos após a administração dos fármacos. O mesmo procedimento foi utilizado no segundo dia pós-incisão. As expressões proteicas dos receptores opioide ? (DOR) e µ (MOR) foram avaliadas usando técnica de immunoblotting de gânglios de raízes dorsais homolaterais (L3, L4, L5 e L6) de grupos de animais sem incisão e após 1, 2, 3 e 7 dias de...

BACKGROUND: Tramadol is known as a central acting analgesic drugused for the treatment of moderate to severe pain. Local analgesic effect was already demonstrated. It is in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect in postoperative pain is not known. In this study, we examined the role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision pain model. METHODS: Young male Wistar rats were submitted to plantar incision and in the first postoperative day (POD1) were divided into four groups:IP I-SF/SF,50 uL of 0.9% NaCl solution were injected in the plantar aspect of the homolateral hindpaw and again after 15 minutes; IP II-SF/T_homo, 50 uL of 0.9% NaCl solution were injected in the plantar aspect of the homolateral hindpaw and, 15 minutes later, 50 µL of solution containing 5 mg tramadol were injected in the same hindpaw; IP III-SF/T_contra, 50 uL of 0.9% NaCl were injected in the plantar aspect of the contralateral hindpaw and, 15 minutes later, 50 uL of solution containing 5 mg tramadol were injected in the same hindpaw; IP IVNal/T_homo, 50 uL of naloxone (200 ug) solution were injected in the homolateral hindpaw and 15 minutes later 50 µL of solution containing 5 mg tramadol were injected. Before receiving the assigned drugs, baseline withdrawal thresholds for mechanical hyperalgesia using electronic von Frey were measured, then, after receiving the assigned drugs, withdrawal thresholds were measured at 15, 30, 45 and 60 min after drug injection. The same procedure was repeated in POD2. u opioid receptor (MOR) and opioid receptor (DOR) protein expressions were evaluated using immunoblotting after removal of ipsilateral dorsal root ganglia (L3, L4, L5 and L6) in groups of rats non submitted to plantar incision and 1, 2, 3 and 7 days after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia...

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis? / Os receptores opioides desempenham papel na patogênese da resposta inflamatória na pancreatite aguda?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.

Receptores opioides até o contexto atual / Opioid receptors to date

JUSTIFICATIVA E OBJETIVOS: Devido à finalidade do ambulatório e os fármacos utilizados rotineiramente, o objetivo deste estudo foi rever e atualizar os conhecimentos sobre os receptores opioides e como complemento de estudo após palestra apresentada aos integrantes da equipe. CONTEÚDO: Foram revisados desde os aspectos históricos até os conhecimentos mais recentes sobre receptores opioides, descritos seus subtipos e mecanismos de ação. Para tal, foram consultadas referências indexadas pelo Pubmed. CONCLUSÃO: Com os dados presentes na literatura atual, concluiu-se que ainda existe muito a ser pesquisado sobre o tópico, visando medicações mais seguras e novas técnicas biomoleculares ainda são necessárias.

BACKGROUND AND OBJECTIVES: Due to the objective of the outpatient setting and to routinely used drugs, this study aimed at reviewing and updating the knowledge about opioid receptors and worked as a study complement after a lecture presented to team members. CONTENTS: We have reviewed from historical aspects to most recent developments about opioid receptors, in addition to describing subtypes and action mechanisms. For such, Pubmed-indexed references were queried. CONCLUSION: After reviewing current literature data, we have concluded that there is still a lot to be researched about the topic, aiming at safer drugs, and new biomolecular techniques are still needed.

Tapentadol, una nueva opción terapéutica: [revisión] / Tapentadol a new therapeutic option: [review]

Introducción. La dolencia o disfunción periférica se asocia a un fenómeno sensorial que incluye síntomas tanto de pérdida de función como de generación de dolor. Los opioides proporcionan alivio en muchos estados de dolor; sin embargo, tienen una potencia y una eficacia reducidas sobre un dolor neuropático. Objetivo. Presentar una revisión actualizada de la literatura sobre tapentadol, con el fin de quesirva, de manera práctica, como una guía. Metodología. Se realizó una búsqueda bibliográfica en las bases de datos Cochrane, PubMed y Embase; se obtuvieron 66 artículos, y de estos se seleccionaron los artículos con la información relevante sobre el tapentadol. Resultados y conclusiones. La terapia de combinación mediante el uso de agonistas del receptor opioide µ, junto a inhibidores de la recaptación de noradrenalina, ha ido ganando adeptos durante los últimos años, como alternativa para tratar los diversos mecanismos que subyacen al dolor neuropático. No obstante, si bien los fármacos inhibidores de la recaptación de noradrenalina son bien tolerados, su eficacia analgésica a menudo no es satisfactoria, y, por su parte, los opioides suelen ofrecer problemas de tolerabilidad; recientemente se ha introducido en el mercado el tapentadol, que combina en una misma molécula acciones de ambos mecanismos de acción, lo cual supone una novedosa, mejorada y eficiente alternativa a la terapia analgésica.

Introduction: The peripheral dysfunction or illness is associated to the sensory phenomenon that includes both symptoms of loss of function as well as pain generation. Opioids provide relief from many pain settings; however they have reduced potency and efficacy for neuropathic pain. Objective. Provide a current review of the literature about tapentadol that could be used as a guide. Methodology. A literature search on the Cochrane, PubMed and Embase databases retrieved 66 papers, and from these, the papers with relevant information about tapentadol were selected. Results and Conclusions. The therapeutic combination of the μ opioid receptor agonists with inhibitorsof the norepinephrine reuptake have become more popular recently as an alternative to treat the mechanisms responsible for neuropathic pain. However, even though the inhibitors ofthe norepinephrine reuptake are well tolerated, their analgesic efficacy is usually unsatisfactory, and opioids usually have tolerability problems;the recent introduction of tapentadol, which combines in the same molecule both mechanisms of action can represent a novel, improved and efficient alternative for analgesia.

Avaliação da expressão e ativação de receptores opióides após injúria periférica em ratos / Evaluation of expression and activation of opioid receptors after peripheral injury in rats

Este trabalho teve como objetivo avaliar os mecanismos envolvidos no aumento da eficácia analgesia da crotalfina (CRF), um peptídeo com atividade tipo opióide, na vigência de inflamação (prostaglandina E2/PGE2) ou lesão tecidual (constrição crônica do nervo isquiático/CCI). A PGE2 (intraplantar), em ratos, aumentou a expressão gênica e protéica de receptores opióides do tipo m e k, no gânglio da raiz dorsal (DRG) e nervo da pata (NP), quando comparado a animais naive. A CCI aumentou a expressão de receptores m e d, no DRG e diminuiu os níveis de receptores k. Embora a PGE2 e CCI, per se, não ativem receptores opióides o CRF e agonistas opióides acarretam maior ativação destes receptores na vigência de sensibilização por PGE2 e CCI. Ainda, o CRF ativa a via das MAPKs (ERK1/2 e JNK), apenas na presença de PGE2, efeito mediado por receptores do tipo k e PKCz. Estes dados mostram que a expressão e ativação de receptores opióides são diferentemente regulados pela injúria aguda ou crônica.

This study aimed to evaluate the mechanisms involved in the increased analgesic efficacy of crotalphine (CRP), an opioid-like peptide, under inflammation prostaglandin E2 (PGE2) and tissue injury (chronic constriction injury/CCI). PGE2 (intraplantar) in rats, increases the genic and proteic expression of m- and k-opioid receptors in the dorsal root ganglia (DRG) and nerve paw (NP), when compared to naïve rats. CCI up-regulates the expression of m and d -opioid receptors in DRG and NP. In contrast, k-opioid receptors were down-regulated by CCI. Although PGE2 and CCI, per se, do not activate opioid receptors, CRP and opioid agonists lead to a higher activation of these receptors in NP slices under PGE2 or CCI sensitization or in DRG cells incubated with PGE2. Moreover, CRP activates ERK1/2 and JNK MAPKs pathways, k-receptor and PKCz-mediated, only when the cells were pre-incubated with PGE2. These data indicate that the expression and activation of opioid receptors are distinctly regulated by the presence of acute or chronic injury.

Cardioprotection conferred by exercise training is blunted by blockade of the opioid system

OBJECTIVES: To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies of myocardial protection (opioid infusion and brief periods of ischemia-reperfusion) preceding irreversible left anterior descending coronary ligation. INTRODUCTION: The acute cardioprotective effects of exercise training are at least partly mediated through opioid receptor-dependent mechanisms in ischemia-reperfusion models. METHODS: Male Wistar rats (n = 76) were randomly assigned to 7 groups: (1) control; (2) exercise training; (3) morphine; (4) intermittent ischemia-reperfusion (three alternating periods of left anterior descending coronary occlusion and reperfusion); (5) exercise training+morphine; (6) naloxone (a non-selective opioid receptor blocker) plus morphine; (7) naloxone before each exercise-training session. Myocardial infarction was established in all groups by left anterior descending coronary ligation. Exercise training was performed on a treadmill for 60 minutes, 5 times/week, for 12 weeks, at 60 percent peak oxygen (peak VO2). Infarct size was histologically evaluated. RESULTS: Exercise training significantly increased exercise capacity and ΔVO2 (VO2 peak - VO2 rest) (p<0.01 vs. sedentary groups). Compared with control, all treatment groups except morphine plus naloxone and exercise training plus naloxone showed a smaller infarcted area (p<0.05). No additional decrease in infarct size occurred in the exercise training plus morphine group. No difference in myocardial capillary density (p = 0.88) was observed in any group. CONCLUSIONS: Exercise training, morphine, exercise training plus morphine and ischemia-reperfusion groups had a smaller infarcted area than the control group. The effect of chronic exercise training in decreasing infarct size seems to occur, at least in part, through the opioid receptor stimulus and not by increasing ...

Endofenotipos en el trastorno límite de la personalidad: enfoque en la neurobiología del apego / Endophenotypes in borderline personality disorder: approach to the neurobiology of attachment

En este trabajo se integra el modelo de apego (conductas maternantes) en su dimensión psicopatológica aplicado al trastorno límite de la personalidad y los descubrimientos neurocientíficos recientes de la base genética de los endofenotipos de hipersensibilidad de las relaciones interpersonales asociados con la inestabilidad afectiva y la impulsividad. Para este propósito, el autor con 20 años de experiencia en el tratamiento de estos pacientes, realiza una puesta al día de dos modelos neuroquímicos, el modelo opioide y una actualización del modelo serotonérgico que explicarían manifestaciones clínicas altamente frecuentes en el TLP: afectos disfóricos, afectos negativos, ansiedades de abandono e intolerancia a la soledad y conductas autoagresivas, entre otros. Se propone que la base genética para estas conductas y su posible grado de heredabilidad se encuentra relacionada con el polimorfismo de genes que controlan la síntesis del receptor para la recaptación de serotonina y la síntesis de receptores tipo Mu en áreas cruciales para el procesamiento emocional y la regulación de la conducta: el cerebro límbico y sus conexiones recíprocas con la corteza prefrontal. Se describen las evidencias experimentales que sustentan esta relación y la posible aplicación para la terapia farmacológica. Se concluye que el trastorno límite de la personalidad representa una vía final común de múltiples dominios alterados a partir de interacciones complejas entre factores ambientales y factores genéticos.

In this work, the author sets out the relationships that can be established between the psychopathology of attachment (maternal behavior) and its influence, together with the generation of endophenotypes of hypersensitivity to interpersonal relationships, associated with emotional instability and impulsiveness. For such purpose, the author, who has more than 20 years experience in the treatment of these patients, provides an update of two neurochemical models, the opioid odel and an update of the serotonergic model which might account for clinical manifestations which are highly frequent in BDP: dysphoric affections, negative affections, abandonment anxieties and intolerance to loneliness and self-aggresive behaviors, among others. The author proposes that the genetic basis for these behaviours and their possible degree of inheritance is related with the genetic polymorphism controlling the receptor synthesis for serotonin reuptake and the synthesis of Mu receptor types in key areas of emotinal processing, and the regulation of behavior: the limbic brain and its reciprocal connections with prefrontal cortex. There is a description of the experimental evidences supporting this relationship ant the possible application in pharmacological therapy. The author conculudes that borderline personality disorder represents a final common pathway of multiple disrupted domains, based upon complex interactions between environmental factors and genetic factors.

Participation of endogenous opioids in the antinociception induced by resistance exercise in rats

Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group): untrained rats (control group); an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group), and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group). The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction) was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37 percent, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15 percent after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.

Avaliação da analgesia controlada pelo paciente no pós-operató-rio de cirurgia cardíaca, com infusão continua de morfina / Evaluation of patient-controlled analgesia in the postoperative period of heart surgery with morphine continuous infusion

Justificativa e objetivos: A bomba de analgesia controlada pelo paciente (ACP) permite que sejam administrados opioides de forma segura e em diferentes programações. O objetivo deste estudo foi avaliar a analgesia, efeitos colaterais e o consumo analgésico de pacientes em pós operatório de cirurgia cardíaca que utilizaram ACP na programação contínua mais bolus com morfina, por via venosa. Método: Estudo prospectivo unicêntrico. O acompanhamento foi realizado a partir da extubação dos pacientes a cada 6h,até 30h. Foram analisadas as seguintes variáveis: intensidade de dor, o consumo de analgésico, número de solicitações de analgésicos e ocorrência de efeitos colaterais.Resultados: A ausência da dor foi verificada em 86 por cento dospacientes, os efeitos colaterais predominantes foram náuseas e vômitos, houve diminuição significante no consumo e nasolicitação de morfina. Conclusão: A programação contínua mais bolus foi segura e eficaz no controle da dor.

Background and objectives: Patient-controlled analgesia pump (PCA) allows for the safe administration of opioids in different schedules. This study aimed at evaluating analgesia, side-effects and analgesic consumption of patients in the postoperative period of heart surgery using intravenous PCA incontinuous infusion plus morphine bolus. Method: Prospective study carried out in a hospital of São Paulo. Patients were followed-up as from extubation every 6 h,until 30h. The following variables were evaluated: pain intensity, analgesic consumption, lumber of analgesic requests and side effects. Results: There has been no pain in 86 per cent of patients. Predominant side-effects were nausea and vomiting with significant decrease in morphine consumption and request. Conclusion: Continuous infusion plus bolus is safe and effective to control pain.

Opioidergic orofacial antinociception induced by electroacupuncture at acupoint St36

The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 ± 0.1; 30 Hz: 1.8 ± 0.1; 100 Hz: 1.7 ± 0.1 vs 1.4 ± 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 ± 0.2 vs 1.0 ± 0.1) was used, and not with 5 or 30 Hz (1.2 ± 0.2 and 0.7 ± 0.1 vs 1.0 ± 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 ± 0.2 and 1.7 ± 0.2 vs 3.0 ± 0.1).

Morphine: axon regeneration, neuroprotection, neurotoxicity, tolerance, and neuropathic pain

Opioids have been used medicinally for millennia for their potent effects on nociception. However, the past 20 years have led to important insights into the influences and mechanisms of opioid actions, which are more extensive than merely analgesia, including human synthesis of opioids, critical roles of opioids during development and following nerve injury, and actions of different opiate alkaloids and their receptors. Due to the vast literature on opioids, the scope of this review has been limited to opioid actions in maintaining neuron viability during development, promoting neurological function following nerve injuries, in inflammation, disease and against ischemia; alleviating neuropathic pain; raising and lowering cellular immunity; and mechanisms modifying morphine tolerance.

Nuevos antiarrítmicos en lafibrilación auricular / New antiarrhythmic agents in atrial fibrillation

The convenience to count with a safe and effective pharmacological wealth for atrial fibrillation treatment had conduced, in a way, to a deep depuration of the vast array of antiarrhythmic drugs, keeping only a very restricted number of compounds with a widely proved anti-atrial activity. On the other hand, it had lead to the discovery of the pathophysiological concepts that point to novel therapeutic targets. Within these objectives is that new antiarrhythmic drugs with preferential, even selective, activity on myocardial atrium ion channels had been developed. Among these new antiarrhythmics, dofetilide, and AVE0118, are taken into account. In addition, new possibilities are opened based on the knowledge of the cardioprotective-antiarrhythmic qualities of the opioidergic system.

Avaliação da analgesia pós-operatória em pacientes submetidos à cirurgia orificial com anestesia local associada ou não à morfina / Evaluation of the postoperative analgesia in patients submitted to anorectal surgery with local anesthesia associated or not the morphine

Ainda não esta comprovada a eficácia dos derivados morfínicos ao nível de receptores opióides periféricos. Estudos procuram demonstrar o poder da droga em interferir na intensidade da dor quando infiltrada em nervos periféricos. Avaliamos, então, a infiltração local de morfina associada à anestesia local em cirurgias orificiais proctológicas. Nesse estudo foram analisados 61 pacientes, independentemente do gênero, sendo divididos aleatoriamente em dois grupos: a um grupo foi associada morfina ao anestésico local enquanto ao outro houve a administração do anestésico local sem a droga morfínica. Os pacientes de ambos os grupos foram submetidos à sedação e analgesia pós-operatória padronizadas. Foram avaliados: a intensidade da dor, a analgesia pós-operatória e a morbidade. A intensidade da dor, no momento de seu surgimento, foi semelhante nos dois grupos; o tempo de analgesia pós-operatória foi maior no grupo em que a morfina foi administrada, entretanto, não se mostrou estatisticamente significativo; as complicações pós-operatórias foram irrelevantes nos dois grupos. Dessa forma, a infiltração local de morfina na região anorretal tem benefícios em relação à analgesia pós-operatória que não mostraram significância estatística e não aumenta a incidência dos efeitos colaterais tão temidos relacionados às drogas morfínicas como retenção urinária e prurido.

It has not been proved the efficacy of morphine derived at periphery opium receivers. Studies are trying to demonstrate the power of the drug to interfere in the intensity of surgical pain while infiltrating in the periphery nerves. This study evaluated the infiltration of morphine associated with local anesthesia in anorectal surgery. Sixty one patients were analyzed, male and female, divided in two groups: in one group was associated morphine in the local anesthesia while in the other group only the local anesthetic was used. The patients of both groups were submitted to the same protocol standardized sedative during the surgery and postoperative analgesia. The intensity of pain was evaluated when it appeared, the time with analgesia was analyzed and other complications were registered. The intensity of pain was similar in both groups, the time with analgesia was longer in the group where morphine was used, although it was not significant in the statistics and the complications after the surgery were not significant in both groups. So the infiltration of morphine in the anorectal region has benefices in the postoperative analgesia but it was not significant in the statistics and it does not increase the complications related with morphine as urinary retention and itching.