Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Erosive Effect of Analgesics on Primary Tooth Enamel - An in Vitro Study

Abstract Objective: To evaluate in vitro erosive effect of analgesics on primary tooth enamel. Material and Methods: The pH and the titratable acidity measurements of the medicines were performed in triplicate using a digital pH meter. Enamel slabs of primary teeth flat and polished were selected by initial surface microhardness analysis. Medications were selected and specimens were assigned into five groups (n=12): Dalsy; Magnopyrol; Paracetamol; Tylenol; and distilled water (negative control). Specimens were immersed in 5 ml of each group solution for 30 min, 4x/day for three days and stored in artificial saliva at 37 °C between immersions and at night. Final microhardness was determined. The data were submitted to Oneway ANOVA and Tukey's test. Scanning electron microscopy (SEM) analysis was performed in three specimens of each group. Results: Medicines showed acidic pH and mean values of titratable acidity ranged from 1.46 to 11.66 ml of 0.1N NaOH. The mineral loss of Magnopyrol was statistically significant in relation to the control group (p<0.01). Magnopyrol showed higher values when compared to Tylenol (p<0.05). SEM images displayed microstructure alterations in the Paracetamol group. Conclusion: Despite the low pH values, only Magnopyrol showed greater enamel softening. Paracetamol demonstrated morphological changes in primary tooth enamel (AU).

Analgesic effects of Phα1ß toxin: a review of mechanisms of action involving pain pathways

Phα1ß is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1ß to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1ß (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1ß antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

Analgesic effects of Phalfa1 beta toxin: a review of mechanisms of action involving pain pathways

Phα1ß is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1ß to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1ß (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1ß antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.

Antinociceptive and anti-inflammatory effects of cellular and extracellular extracts from microalga Chlamydomonas pumilioniformis on mice

Microalga species have attracted interest as a source of bioactive compounds with several pharmacological activities. Previous studies reported that microalgae from the genus Chlamydomonas have anti-inflammatory and antioxidant properties. In this study, antinociceptive and anti-inflammatory activities of two extracts from microalga Chlamydomonas pumilioniformis were investigated. Cellular and extracellular extracts were prepared from a 14 day-batch culture in WC medium at the end of exponential growth and their carbohydrate contents were determined. Antinociceptive effects of extracts were evaluated by writhing and formalin-induced nociception tests, while the anti-inflammatory activity was analyzed by formalin-induced paw edema in mice. The analysis of dissolved carbohydrates detected amounts of 90 and 20 µg mL-1 of total carbohydrate in cellular and extracellular extracts, respectively. Cellular extract was mainly composed of glucose, but with significant proportions of arabinose, galactose and mannose and/or xylose and minor ones of fucose, rhamnose, amino sugars and uronic acids. Extracellular extract was composed of a similar proportion of glucose, galactose and mannose/xylose, besides significant ones of arabinose, fucose and galacturonic acid. Intraperitoneal administration of extracts significantly reduced writhing response in mice. In the formalin test, the extracellular extract inhibited both formalin phases, while the cellular extract was only effective in the late phase. Furthermore, extracts reduced the formalin-induced paw edema. In sum, we showed, for the first time, that C. pumilioniformis can be an important source of polysaccharides with anti-inflammatory and antinociceptive effects.

Impulsivity prevalence in migraine patients without and with medication overuse / Prevalência de impulsividade em pacientes com enxaqueca sem e com abuso de medicação

ABSTRACT Background: Migraine is one of the most common disorders in neurological clinical practice and is part of the group of primary headaches. It often affects individuals in the age group of 25-55 years, when people are at their peak of economic productivity. Many patients ultimately overuse analgesics. Overuse is defined by the use of analgesics for at least 15 times a month - within a minimal three-month period. Impulsivity and migraine cause losses in the lives of individuals suffering from them, as they can compromise these individuals' social, emotional, and professional spheres. Regarding the professional sphere, it results in economic losses compared with the overall population. Objective: To investigate the presence of impulsive behavior in patients with migraine and with medication-overuse migraine. Methods: Cross-sectional study on 210 female and male patients; 140 were diagnosed with migraine according to criteria of the International Classification of Headache Disorders and were subdivided into two groups (70 patients each). One of these groups was composed of medication-overuse patients; the control group was composed of non-migraine patients (70 patients). All patients were evaluated with the Barratt Impulsivity Scale (BIS-11). Results: The group of migraine patients accounted for the highest impulsivity level, followed by the control group and, finally, by the medication-overuse group. However, these differences did not attain statistical significance. Conclusions: It was not possible to establish a clear connection between migraine and impulsive behavior. Association was higher among migraineurs without medication overuse.

RESUMO Introdução: A enxaqueca é uma das condições mais comuns na prática clínica neurológica, enquadrando-se no grupo das cefaleias primárias. Sua prevalência é maior na faixa etária de 25 a 55 anos, coincidindo com o pico da produtividade econômica. Muitos pacientes recorrem ao uso abusivo de analgésicos. O uso excessivo desses medicamentos é definido pela sua utilização por pelo menos 15 vezes ao mês, por um período de no mínimo três meses. A impulsividade e a enxaqueca causam prejuízos na vida dos indivíduos afetados, podendo comprometer os âmbitos social, emocional e profissional, resultando em um prejuízo monetário a esse grupo, em relação à população em geral. Objetivo: Investigar a presença de comportamento impulsivo em pacientes com enxaqueca com abuso de analgésico. Métodos: Estudo de corte transversal com 210 pacientes, homens e mulheres, sendo 140 com diagnóstico de enxaqueca segundo os critérios da Classificação Internacional das Cefaleias (IHCD-3), subdivididos em dois grupos de 70 pacientes cada, um composto por pacientes em uso excessivo de medicamentos, e um grupo controle composto por indivíduos sem enxaqueca. Todos os pacientes foram avaliados com a Escala de Impulsividade de Barratt - BIS 11. Resultados: O grupo com enxaqueca apresentou maior impulsividade, seguido do grupo controle e, por fim, o grupo com enxaqueca com abuso de medicamentos. No entanto, essas diferenças não atingiram significância estatística. Conclusão: Não foi possível encontrar relação direta entre a enxaqueca e comportamentos impulsivos. No entanto, esta relação foi maior entre os pacientes com enxaqueca sem abuso de analgésico.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality / Prevalencia de delirio en pacientes de cuidados intensivos y asociación con la sedoanalgesia, gravedad y mortalidad / Prevalência de delirium em pacientes de terapia intensiva e associação com sedoanalgesia, gravidade e mortalidade

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.

RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.

RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.

La determinación económica, social y laboral de la enfermedad renal crónica de causas no tradicionales (ERCnT) en la costa sur de Guatemala / The economic, social and labor determination of chronic kidney disease of non-traditional causes (CKDnT) on the southern coast of Guatemala

La flexibilidad laboral es característica de la producción estacional agroindustrial, cuyo principal problema es aprovechar con intensidad los períodos en los que se incrementa la producción. Pero, ¿cómo la demandante competitividad laboral influye en las estrategias de los trabajadores para incrementar su productividad? A partir de esta pregunta, se identificaron los aspectos económicos, sociales y laborales que inciden en la salud, así como las respuestas para disminuir el dolor físico y aumentar las exigencias de competitividad, flexibilización y desregularización del mercado de trabajo. La exposición ambiental y ocupacional en las condiciones de trabajo, el estrés térmico asociado a la deshidratación en la actividad física intensa, el limitado acceso a los servicios de salud, la mala alimentación y la pobre calidad de vida, también pueden producir otras enfermedades como diabetes e hipertensión, así como infecciones y lesiones renales. En ese contexto, en los últimos 20 años, se empezaron a reportar casos de enfermedad renal. La metodología cualitativa aplicada a este estudio, permitió llevar a cabo un proceso investigativo descriptivo e interpretativo sobre la forma en que los sujetos interactúan. Para ello se utilizaron las trayectorias laborales como técnicas en la recolección de datos. Los resultados arrojaron información relevante sobre las estrategias que los trabajadores utilizan para incrementar su rendimiento laboral, entre ellas la automedicación de vitaminas y analgésicos para tratar los espasmos musculares, que estimulan el sistema nervioso central, así como de bebidas saborizadas y energizantes con posibles repercusiones en la excreción renal.

Labor flexibility is characteristic of seasonal agroindustrial production whose main problem is to take advantage of the periods in which production increases. But, how does this demanding labor competitiveness influence workers' strategies to increase their productivity? From this question, the economic, social and labor aspects that affect health were identified, as well as the answers to reduce physical pain and increase the demands for competitiveness, flexibility and deregulation of the labor market. Environmental and occupational exposure in working conditions, thermal stress associated with dehydration in intense physical activity, limited access to health services, poor diet and quality of life, can also cause other diseases such as diabetes and hypertension, as well as infections and kidney lesions. In that context, in the last 20 years, cases of kidney disease began to be reported. The qualitative methodology applied to this study, allowed to carry out a descriptive and interpretive investigation process on the way in which the subjects interact, for this, the work trajectories were used as techniques in data collection. The results yielded relevant information on the strategies that workers use to increase their work performance, including self-medication of "vitamins" and analgesics to treat muscle spasms, drugs that stimulate the central nervous system, as well as flavored and energizing drinks with possible repercussions on renal excretion.

Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality / Prevalencia de delirio en pacientes de cuidados intensivos y asociación con la sedoanalgesia, gravedad y mortalidad / Prevalência de delirium em pacientes de terapia intensiva e associação com sedoanalgesia, gravidade e mortalidade

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.

RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.

RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.

Effect of melatonin on the daytime sleepiness side-effect of gabapentin in adults patients with neuropathic pain / Efeito da melatonina sobre o efeito colateral de sonolência diurna da gabapentina em pacientes adultos com dor neuropática

Abstract Background and objectives: Gabapentin is an antiepileptic drug. Widely used for the management of neuropathic pain. Although it is known to be well tolerated, somnolence and dizziness are the most frequent adverse effects. In this study, we aimed to evaluate the effect of melatonin on daytime sleepiness side effect of gabapentin, sleep quality and pain intensity of patients with neuropathic pain. Methods: Patients suffering from "neuropathic pain" and planed to receive gabapentin therapy were randomly divided into two groups. Group 1 received melatonin 3 mg and gabapentin 900 mg orally, group 2 received matching placebo capsule and gabapentin 900 mg. The Epworth Sleepiness Scale, the Pittsburgh sleep quality index for assessment of sleep quality and Verbal Rating Scale were completed at the 0th, 10th and 30th days of treatment. Additive analgesic drug requirements were recorded. Results: Eighty patients were enrolled to the study; age, gender, ratio of additive analgesic consumption, baseline Epworth Sleepiness Scale, Pittsburg Sleep Quality index and Verbal Rating Scale scores were similar between the groups. Epworth Sleepiness Scale scores, Pittsburgh sleep quality index scores and Verbal Rating Scale scores in Group 1 were significantly lower than group 2 at the 10th day of treatment (p = 0.002, p = 0.003, p = 0.002 respectively). At the 30th day of treatment, Epworth Sleepiness Scale scores and Verbal Rating Scale scores were significantly lower in Group 1 (p = 0.002, p = 0.008 respectively). However, Pittsburgh sleep quality index scores did not significantly differ between the groups (p = 0.0566). Conclusions: Melatonin supplementation rapidly and significantly improved daytime sleepiness side-effect of gabapentin, however sleep quality of the patients with neuropathic pain was similar between groups.

Resumo Justificativa e objetivos: Gabapentina é um agente antiepiléptico, amplamente utilizado para o tratamento da dor neuropática. Embora conhecida por ser bem-tolerada, sonolência e tontura são os seus efeitos adversos mais frequentes. Neste estudo, nosso objetivo foi avaliar o efeito da melatonina sobre o efeito colateral de sonolência diurna da gabapentina, a qualidade do sono e a intensidade da dor em pacientes com dor neuropática. Métodos: Os pacientes que sofriam de "dor neuropática" e com prescrição para receber terapia com gabapentina foram divididos aleatoriamente em dois grupos. O Grupo 1 recebeu 3 mg de melatonina e 900 mg de gabapentina por via oral, o Grupo 2 recebeu uma cápsula de placebo correspondente e 900 mg de gabapentina. A escala de sonolência de Epworth (ESS), o índice de qualidade do sono de Pittsburgh para avaliação da qualidade do sono (PSQI) e a escala de avaliação verbal (VRS) foram aplicados nos dias 0, 10 e 30 de tratamento. A necessidade de medicamentos analgésicos adicionais foi registrada. Resultados: Oitenta pacientes foram incluídos no estudo; idade, sexo, quantidade de analgésico adicional consumida e os escores basais de ESS, PSQI e VRS foram semelhantes entre os grupos. Os escores ESS, PSQI e VRS do Grupo 1 foram significativamente menores que os do Grupo 2 no décimo dia de tratamento (p = 0,002, p = 0,003, p = 0,002, respectivamente). No trigésimo dia de tratamento, os escores ESS e VRS foram significativamente menores no Grupo 1 (p = 0,002, p = 0,008, respectivamente). No entanto, os escores PSQI não diferiram significativamente entre os grupos (p = 0,0566). Conclusões: A suplementação de melatonina melhorou de forma rápida e significativa o efeito colateral de sonolência diurna da gabapentina, mas a qualidade do sono dos pacientes com dor neuropática foi semelhante entre os grupos.

O efeito analgésico da pregabalina e do sulfato de magnésio no pós-operatório da mastectomia com linfadenectomia axilar / Analgesic effect of pregabalin and magnesium sulfate post-mastectomy with axillary lymphadenectomy

Introdução: A mastectomia com linfadenectomia é uma cirurgia que causa dor moderada ou severa no pós-operatório imediato. Têm sido muito pesquisadas drogas adjuvantes, seguras, que promovam boa analgesia e com poucos efeitos adversos. Dentre essas drogas estão a pregabalina e o sulfato de magnésio. Objetivo: Avaliar e comparar o efeito analgésico da pregabalina e do sulfato de magnésio no pós-operatório da mastectomia com linfadenectomia axilar. Metodologia: Estudo randomizado e triplo-cego. Oitenta pacientes submetidas a mastectomia com linfadenectomia axilar sob anestesia geral foram divididas em 4 grupos: Controle (GC) não usaram a medicação adjuvante proposta; Magnésio+Placebo (GM) receberam apenas sulfato de magnésio durante a anestesia; Pregabalina+Magnésio (GP+M), utilizaram a mesma dose de magnésio acrescida de pregabalina 150 mg antes e 12 horas após a cirurgia; e o Pregabalina+Placebo (GP) receberam apenas a pregabalina. Todas as pacientes responderam o questionário SRQ-20 para rastrear possível transtorno mental e foram seguidas, monitorando o estado físico 1h 12h e 24h após a cirurgia, através de anamnese, questionário de dor, necessidade de utilização de opióides e presença de complicações e/ou eventos adversos como náusea, vômito e sonolência. Resultado: O número de pacientes apresentando dor ausente/leve no GP+M foi significantemente maior que nos GC, GM e GP após uma hora. Após 12 horas, GP+M e GP apresentaram maior número de pacientes com dor ausente/leve que GC e GM. Em 24 horas do pós-operatório, todos os pacientes de todos os grupos avaliados não apresentaram dor moderada/severa. Não houve diferença na frequência de pacientes apresentando náusea ou vômito, nem nos escores da avaliação do sono após a cirurgia nos quatro grupos. Conclusão: A associação de sulfato de magnésio e pregabalina causa boa analgesia de mastectomia com linfadenectomia axilar na primeira hora do pós-operatório, no entanto o uso isolado do sulfato de magnésio não trouxe benefício para analgesia nestas pacientes, assim como a pregabalina sozinha se mostrou pouco efetiva na primeira hora de avaliação

Introduction: Mastectomy and lymphadenectomy are associated with moderate to severe pain immediately after surgery. Several reportedly ffective and safe analgesics are available, including pregabalin and magnesium sulfate. Objective: To evaluate and compare the analgesic effect of pregabalin and magnesium sulfate after mastectomy with axillary lymphadenectomy. Methodology: Double-blind, randomized study involving 80 patients submitted to mastectomy and axillary lymphadenectomy under general anesthesia. Magnesium sulfate (or placebo) was administered during anesthesia (50 mg/kg; maintenance 10 mg/kg/h), while pregabalin 150 mg (or placebo) was administered before and 12 hours after surgery. The patients were distributed into 4 groups. CG: control (no medication), GM: magnesium sulfate + placebo, GP+M: magnesium sulfate + pregabalin, and GP: pregabalin + placebo. A questionnaire (SRQ-20) was administered to all patients to detect potental mental disorders. The patients' condition was monitored at 1 12 and 24 hours after surgery (anamnesis, pain questionnaire, opioid requirements, complications and/or adverse events such as nausea, vomiting and drowsiness). Results: At 1 hour, the number of patients with mild or no pain was significantly greater in GP+M than in any other group. At 12 hours, mild or no pain was more frequently observed in GP+M and GP than in CG and GM. At 24 hours, no patient reported moderate or severe pain. The four groups did not differ significantly with regard to nausea, vomiting or sleep scores. Conclusion: The combination of pregabalin and magnesium sulfate provided satisfactory analgesia in the first hour after mastectomy with axillary lymphadenectomy. When used alone however, magnesium sulfate had no measurable analgesic effect, and pregabalin was only slightly effective one hour after surgery

Pre-clinical interaction of ayahuasca, a brew used in spiritual movements, with morphine and propofol

ABSTRACT Ayahuasca is a beverage with psychoactive properties used in religious and ceremonial rituals by some religious groups. The main active components of ayahuasca are dimethyltryptamine and the harmala alkaloids with ß-carboline structure acting as monoamine oxidase A inhibitors. This combination produces a pronounced activation of serotonergic pathways and presents potential interaction with other psychotropics. The objective of this study was to investigate the possible interactions between ayahuasca and agents employed in general anesthesia. The pharmacological interactions between ayahuasca and morphine or propofol were evaluated in mice using doses of 12, 120 and 1200 mg/kg (0.1 to 10 times the average dose consumed by humans in religious rituals). Ayahuasca alone showed an antinociceptive effect in the writhing and formalin tests, and intensified the analgesic effect of morphine in the hot plate test. Concerning the pharmacological interactions between ayahuasca and propofol, the results were opposite; ayahuasca intensified the depressant effect of propofol in the rotarod test, but decreased the sleeping time induced by propofol. These set of results showed the occurrence of some interactions between ayahuasca and the drugs morphine and propofol, possibly by both pharmacokinetics and pharmacodynamics mechanisms

Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT

Antinociceptive and anti-inflammatory effects of Lantana camara L. extract in mice / Efeitos antinociceptivos do extrato de Lantana camara L. em camundongos

ABSTRACT: he Lantana camara L. belongs to the family Verbenaceae, which contains several active compounds in leaves and roots and which are reported to have medicinal and insecticidal properties. Studies of plants within the same family show the existence of anti-inflammatory activity in paw edema induced by carrageenan, serotonin and histamine and analgesic activity in the acetic acid writhing and tail-flick tests. The present study investigated whether the L. camara extract (ACE) also exerts these effects. The ACE toxicity was studied in male mice, and the percentage of mortality recorded 7 days after treatment was assessed. The ACE was evaluated as an antinociceptive agent in the hot plate, tail-flick and acetic acid writhing tests at a nontoxic dose of 1.0 g/Kg. The results showed that 1.5 g/Kg of ACE was not able to cause death, and doses of 3.0 and 4.0 g/Kg caused 50% and 60% death, respectively, in male mice. In all of the antinociceptive tests, 1 g/Kg of ACE markedly reduced responses to pain. Our findings suggest that ACE may have active anti-inflammatory and antinociceptive properties in much smaller doses than toxic.

RESUMO: Lantana camara L. pertence à família Verbenaceae, a qual contem muitos princípios ativos em suas folhas e raízes com propriedade medicinais e inseticidas. Estudos com plantas da mesma família mostram a existência de propriedades antinflamatórias no modelo de edema de pata induzido pela carragenina, serotonina e histamina, além da atividade analgésica nos testes de contorção induzida pelo ácido acético e da retirada da cauda por estímulo térmico. O presente trabalho investigou os efeitos tóxicos e antinociceptivos do extrato de L. camara (ACE) em camundongos. Para tanto, investigou-se a porcentagem de mortes em 7 dias após a administração de diferentes doses do extrato. Avaliou-se também os efeitos antinociceptivos do ACE pelos testes da placa quente, estimulação térmica da cauda e contorções abdominais induzidas pelo ácido acético com a dose não-tóxica [1,0 g/Kg]. Os resultados mostraram que 1,5 g/Kg do ACE não causou mortalidade, enquanto que 3,0 e 4,0 g/Kg promoveram 50 e 60% de mortalidade, respectivamente. Em todos os testes antinociceptivos, a dose de 1,0 g/Kg do ACE reduziu a resposta à dor. Os presentes resultados indicam que o ACE apresenta propriedades antinflamatórias e analgésicas em doses muito menores que a tóxica.

Preemptive analgesia effects of Ketamine in patients undergoing surgery. A meta-analysis

PURPOSE: To evaluate the preemptive analgesia effects of ketamine for postoperative pain. METHODS: PubMed, EMBASE and Cochrane Library were searched to identify randomized controlled trials (RCTs) involved in ketamine for preemptive analgesic up to March 2013. The relative risk (RR) or mean difference (MD) as well as the confounding 95% confidence interval (CI) were calculated by the Revman 5.0 software. RESULTS: A total of five studies including 266 patients were included in this meta-analysis. Overall, ketamine could reduce the postoperative morphine consumption and significantly prolong the time to first analgesic (p < 0.00001, MD = 0.91, 95% CI: 0.56 to 1.26). However, there was no significant difference in indicators of nausea and vomiting (p = 0.87, RR = 1.04, 95% CI: 0.67 to 1.60), surgical time (p = 0.41, MD = -2.13, 95% CI: -7.21 to 2.95) and anesthetic time (p = 0.53, MD = -1.54, 95% CI: -6.34 to -3.26) between ketamine and control group. CONCLUSIONS: Ketamine was able to accomplish some preemptive analgesic effects of reducing postoperative morphine consumption and prolonging the time to first analgesic. Meanwhile, ketamine was as safe as physiological saline in side effects of nausea and vomiting. .

Norepinephrine infusion increases urine output in children under sedative and analgesic infusion / Infusão de noradrenalina aumenta o débito urinário de crianças recebendo drogas sedoanalgésicas

Objective: to evaluate the effects of early norepinephrine (NE) infusion in children submitted to mechanical ventilation (MV) requiring continuous sedative and analgesic infusion. Methods: double-blinded, randomized, placebo-controlled trial enrolling children (1 month to 12 years of age) admitted to a Brazilian PICU and expected to require MV and continuous sedative and analgesic drug infusions for at least five days. Children were randomized to receive either norepinephrine (NE) (0.15 mcg/kg/min) or normal saline infusion, started in the first 24 hours of MV, and maintained for 72 hours. We compared hemodynamic variables, fluid intake, renal function and urine output between groups. Results: forty children were equally allocated to the NE or placebo groups, with no differences in baseline characteristics, laboratorial findings, PRISM II score, length of MV, or mortality between groups. The average norepinephrine infusion was 0.143 mcg/kg/min. The NE group showed higher urine output (p = 0.016) and continuous increment in the mean arterial pressure compared to the baseline (p = 0.043). There were no differences in the remaining hemodynamic variables, fluid requirements, or furosemide administration. Conclusion: early norepinephrine infusion in children submitted to MV improves mean arterial pressure and increases urine output. These effects were attributed to reversion of vasoplegia induced by the sedative and analgesic drugs. .

Objetivo: avaliar os efeitos da infusão de noradrenalina (NA) em crianças submetidas a ventilação mecânica (VM) requerendo infusão contínua de sedoanalgesia. Métodos: estudo duplo cego, randomizado e placebo controlado envolvendo crianças de 1 mês a 12 anos, admitidas em uma UTI pediátrica brasileira com a expectativa de necessidade de VM e sedoanalgesia por, no mínimo, 5 dias. As crianças foram randomizadas a receber infusão de NA (0,15 mcg/kg/min) ou solução salina, iniciadas nas primeiras 24 horas de VM e mantidas por 72 horas. Comparamos as variáveis hemodinâmicas, oferta hídrica, função renal e débito urinário entre os dois grupos. Resultados: 40 crianças foram alocadas aos grupos NA e placebo, sem diferenças nas características basais, achados laboratoriais, escore PRISM II, tempo de VM ou mortalidade. A infusão média de NA foi 0,143 mcg/kg/min. O grupo NA apresentou maior débito urinário (p = 0,016) e aumento constante da pressão arterial média quando comparado aos níveis basais (p = 0,043). Não se observou diferenças nas demais variáveis hemodinâmicas, reposição hídrica ou no uso de furosemida. Conclusão: infusão precoce de NA em crianças submetidas a VM em uso sedoanalgesia promove aumento na pressão arterial média e aumento da diurese. Esses efeitos são atribuídos à reversão da vasoplegia induzida pelas drogas sedativas e analgésicas. .