Research progress on the electroencephalogram characteristics of nociception / 临床麻醉学杂志

The effective analysis of electroencephalography(EEG)data to objectively reflect the changes of nociception has been a hot topic of research in recent years.The incidence of moderate to severe postoperative acute pain remains high.Postoperative acute pain seriously affects patients'physical and psy-chological health,yet there is no objective gold standard for measuring perioperative nociception to guide perioperative analgesia.The results of current studies on the characteristics of EEG changes during nociception are contradictory.This paper presents the EEG characteristics of nociception in order to provide a reference for future research design.

Impact of streptozotocin-induced diabetes on experimental masseter pain in rats

Abstract This study aimed to assess the influence of streptozotocin (STZ)-induced diabetes on the nociceptive behavior evoked by the injection of hypertonic saline (HS) into the masseter muscle of rats. Forty male rats were equally divided into four groups: a) isotonic saline control, which received 0.9% isotonic saline (IS), (Ctrl-IS); b) hypertonic saline control, which received 5% HS (Ctrl-HS); c) STZ-induced diabetic, which received IS, (STZ-IS); d) STZ-induced diabetic, which received HS (STZ-HS). Experimental diabetes was induced by a single intraperitoneal injection of STZ at dose of 60 mg/kg dissolved in 0.1 M citrate buffer, and 100 μL of HS or IS were injected into the left masseter to measure the nociceptive behavior. Later on, muscle RNA was extracted to measure the relative expression of the following cytokines: cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukins (IL)-1β, -2, -6, and -10. One-way analysis of variance (ANOVA) was applied to the data (p < 0.050). We observed a main effect of group on the nociceptive response (ANOVA: F = 11.60, p < 0.001), where the Ctrl-HS group presented the highest response (p < 0.001). However, nociceptive response was similar among the Ctrl-IS, STZ-IS, and STZ-HS group (p > 0.050). In addition, the highest relative gene expression of TNF-α and IL-6 was found in the masseter of control rats following experimental muscle pain (p < 0.050). In conclusion, the loss of somatosensory function can be observed in deep orofacial tissues of STZ-induced diabetic rats.

Incorporación a nivel nacional de tecnología no invasiva para valoración del dolor y/o disconfort neonatal / Incorporation of non-invasive technology for the assessment of neonatal pain and/or discomfort at national level / Incorporação a nível nacional de tecnologia não invasiva para avaliação da dor e/ou desconforto neonatal

Introducción: la exposición a estímulos dolorosos y estrés en la etapa neonatal, sin un correcto tratamiento, tiene consecuencias a corto y largo plazo. El diagnóstico adecuado es un desafío, ya que las escalas clínicas son subjetivas y se requieren herramientas de detección con mejor objetividad y capacidad de interpretación del disconfort/dolor neonatal. Newborn Infant Parasympathetic Evaluation (NIPE™) es una tecnología no invasiva de monitorización continua del dolor en neonatos, desarrollada recientemente dada la dificultad de objetivar el dolor mediante los métodos convencionales en la práctica clínica. Esta tecnología se basa en el análisis de la variabilidad de la frecuencia cardíaca (FC), lo que permite aproximarse a la actividad del sistema parasimpático. Objetivos: el objetivo de esta investigación fue valorar el disconfort en un modelo de cerdo recién nacido (RN) y en humanos neonatos expuestos a maniobras nociceptivas con la utilización de tecnología no invasiva (NIPE), en la maternidad del Hospital Universitario. Material y métodos: se realizó un estudio observacional, longitudinal, en seis cerdos RN, anestesiados, monitorizados hemodinámicamente y sometidos a un procedimiento quirúrgico mayor (toracotomía lateral izquierda con abordaje cardíaco, pericardiostomía y acceso vascular pulmonar transventricular derecho) y 12 procedimientos mínimamente invasivos de la práctica clínica habitual, como vacunación BCG, hemoglucotest y pesquisa, que generan un estímulo nociceptivo en ocho RN de término sanos. Se incluyeron RN sanos de término (EG entre 37-41 semanas más seis días) internados en el alojamiento conjunto madre-hijo, se excluyeron de la muestra los RN que presentaron alguna patología y aquellos cuyos padres no aceptaron la participación en el estudio. Resultados: se comparó la variabilidad de la FC mediante detección automatizada (NIPE™) para estimación objetiva del dolor/disconfort. Se comparó en la clínica con una escala validada y ampliamente utilizada en neonatos: Premature Infant Pain Profile (PIPP). Para valorar la asociación entre variables NIPE™ y FC se utilizaron correlación de Spearman, el test de Kruskall-Wallis o test de chi cuadrado con corrección de Fisher, según correspondiera. Se encontró una correlación negativa entre FC y NIPE™ tanto para el grupo de neonatos humanos (r=-1; p=0,008) como para el modelo animal (r=-0,6; p=0,0004). No se encontró asociación significativa entre NIPE™ y la escala PIPP. La variación entre valores de NIPE™ pre y posestímulo en RN humanos fue significativa (p=0,008). Conclusiones: determinamos que en ambos escenarios explorados los valores de NIPE™ descienden ante estímulos nociceptivos y los cambios en la FC se relacionan con sus valores, independientemente de la especie o la agresividad de la maniobra. Este trabajo es el primero a nivel nacional incorporando el uso de esta tecnología, creemos que tendrá impacto en la forma de evaluar y abordar el dolor por parte de los equipos asistenciales y de experimentación.

Introduction: exposure to painful stimuli and stress in the neonatal stage, without correct treatment, has short and long-term consequences. Proper diagnosis is a challenge since clinical scales are subjective, and we require more objective screening tools and a better ability to interpret neonatal discomfort/pain. Newborn Infant Parasympathetic Evaluation (NIPE™) is a non-invasive technology for continuous pain monitoring in neonates, recently developed given the difficulty to objectify pain using conventional methods in clinical practice. This technology is based on the analysis of heart rate variability (HR), which allows us to approximate the activity of the parasympathetic system. Objectives: the objective of this research was to assess discomfort in a newborn pig model (NB) and in human neonates exposed to nociceptive maneuvers with the use of non-invasive technology (NIPE), in the maternity ward of the University Hospital. Material and methods: an observational, longitudinal study was carried out in 6 NB pigs, anesthetized, hemodynamically monitored and subjected to a major surgical procedure (left lateral thoracotomy with cardiac approach, pericardiostomy and right trans ventricular pulmonary vascular access) and 12 minimally invasive procedures, from clinical practice. routine such as BCG vaccination, hemoglucotest and screening, which generate a nociceptive stimulus in 8 healthy term newborns. Healthy term newborns (GA between 37-41 weeks plus 6 days) admitted to the mother-child joint accommodation were included, We excluded those NB patients who presented some pathology or whose parents did not accept participation in the study. Results: HR variability was compared using automated detection (NIPETM) for objective estimation of pain/discomfort. It was compared in the clinic with a validated and widely used scale in neonates: Premature Infant Pain Profile (PIPP). We used the Spearman's correlation, the Kruskall-Wallis test or the Chi square test with Fisher's correction to assess the association between NIPE™ variables and HR, as needed. A negative correlation was found between HR and NIPETM for both the group of neonates. humans (r=-1; p=0.008) and for the animal model (r=-0.6; p=0.0004). No significant association was found between NIPETM and the PIPP scale. The variation between pre- and post-stimulus NIPE™ values in human NBs was significant (p=0.008). Conclusions: we conclude that in both scenarios explored, NIPE™ values decrease when faced with nociceptive stimuli and changes in HR are related to its values, regardless of the species or the aggressiveness of the maneuver. This paper is the first at a national level to incorporate the use of this technology, we believe it will have an impact on the way pain is assessed and addressed by healthcare and experimental teams.

Introdução: a exposição a estímulos dolorosos e ao estresse na fase neonatal, sem tratamento correto, traz consequências a curto e longo prazo. O diagnóstico adequado é um desafio, uma vez que as escalas clínicas são subjetivas e são necessárias ferramentas de triagem com melhor objetividade e capacidade de interpretar o desconforto/dor neonatal. A Avaliação Parassimpática do Recém-Nascido (NIPE™) é uma tecnologia não invasiva para monitoramento contínuo da dor em neonatos, desenvolvida recentemente devido à dificuldade de objetivar a dor usando métodos convencionais na prática clínica. Esta tecnologia baseia-se na análise da variabilidade da frequência cardíaca (FC), o que nos permite aproximar a atividade do sistema parassimpático. Objetivos: o objetivo desta pesquisa foi avaliar o desconforto em recém-nascido modelo suíno (RN) e em neonatos humanos expostos a manobras nociceptivas com uso de tecnologia não invasiva (NIPE), na maternidade do Hospital Universitário. Material e métodos: foi realizado um estudo observacional, longitudinal, em 6 suínos RN, anestesiados, monitorados hemodinamicamente e submetidos a um procedimento cirúrgico de grande porte (toracotomia lateral esquerda com abordagem cardíaca, pericardiostomia e acesso vascular pulmonar transventricular direito) e 12 procedimentos minimamente invasivos, da prática clínica. rotina como vacinação BCG, hemoglicoteste e triagem, que geram estímulo nociceptivo em 8 recém-nascidos a termo saudáveis. Foram incluídos recém-nascidos a termo saudáveis (IG entre 37-41 semanas mais 6 dias) internados no alojamento conjunto mãe-filho, foram excluídos do A amostra incluiu RNs que apresentavam alguma patologia e aqueles cujos pais não aceitaram a participação no estudo. Resultados: a variabilidade da FC foi comparada por meio de detecção automatizada (NIPETM) para estimativa objetiva de dor/desconforto. Foi comparado na clínica com uma escala validada e amplamente utilizada em neonatos: Premature Infant Pain Profile (PIPP). Para avaliar a associação entre as variáveis do NIPE™ e a FC, utilizou-se a correlação de Spearman, o teste de Kruskall-Wallis ou o teste Qui-quadrado com correção de Fisher, conforme apropriado. Foi encontrada correlação negativa entre a FC e o NIPETM para ambos os grupos de neonatos. (r=-1; p=0,008) e para o modelo animal (r=-0,6; p=0,0004). Não foi encontrada associação significativa entre o NIPETM e a escala PIPP. A variação entre os valores de NIPE™ pré e pós-estímulo em RN humanos foi significativa (p=0,008). Conclusões: concluímos que em ambos os cenários explorados, os valores do NIPE™ diminuem diante de estímulos nociceptivos e as alterações na FC estão relacionadas aos seus valores, independente da espécie ou da agressividade da manobra. Este trabalho é o primeiro a nível nacional a incorporar a utilização desta tecnologia, acreditamos que terá impacto na forma como a dor é avaliada e abordada pelas equipas de saúde e experimentais.

Application of dexmedetomidine nasal spray combined with intravenous pumping in oral and maxil-lofacial surgery / 临床麻醉学杂志

Objective To investigate the effect of different modes of administration of dexmedeto-midine pre-nasal spray combined with pumping and conventional pumping on remifentanil and heart rate var-iability(HRV)in patients undergoing oral and maxillofacial surgery.Methods Ninety patients undergoing elective oral and maxillofacial surgery,43 males and 47 females,aged 18-64 years,BMI 18-25 kg/m2,ASA physical status Ⅰ or Ⅱ,were selected.The patients were divided into three groups by random number table method:pre-nasal spray combined with pump injection group(group PP),conventional pump injection group(group CP),and control group(group C),30 cases in each group.Patients in group PP were given a nasal spray of dexmedetomidine at a dose of 0.5 μg/kg,group CP and group C were given the same amount of normal saline by the same method 45 minutes before entering the room on the day of surgery.Dexmedetomidine was injected intravenously in group PP at doses of 0.5 μg/kg and in group CP at dose of 1 μg/kg for 10 minutes,and group C was given the same amount of normal saline 10 minutes before induc-tion of anesthesia.Ramsay sedation score on admission,duration of surgery,the dose of remifentanil during induction and maintenance of anesthesia,room admission(T1),induction intubation(T2),10 minutes after skin incision(T3),and extubation(T4),RMSSD,SDNN,LF,HF,TP,LF/HF ratio and other HRV analysis indicators,HR,MAP,and BIS values were recorded.The incidence of PONV and the use of analgesics within 24 hours after operation were recorded.Results Compared with group C,the MAP was significantly reduced,RMSSD,SDNN,and logTP were significantly increased,and LF/HF was significantly decreased in group PP at T,(P＜0.05),the LF/HF were significantly reduced in groups PP and CP at T2-T4(P＜0.05),the dosage of remifentanil during the anesthesia induction,the incidence of PONV,and the use rate of analgesic drugs in 24 hours were significantly reduced in groups PP and CP(P＜0.05).Compared with group CP,the RMSSD,SDNN,logLF,logHF,and logTP were increased sig-nificantly in group PP at T,(P＜0.05),the logHF were increased significantly in group PP at T2 and T4(P＜0.05),the Ramsay sedative evaluation was increased significantly,the dosage of remifentanil was sig-nificantly reduced during the maintenance of anesthesia in group PP(P＜0.05).Conclusion After the use of dexmedetomidine,the indicators related to stress level in HRV analysis were significantly reduced,and the dosage of opioids was significantly reduced.The use of dexmedetomidine pre-nasal spray combined with pump injection can further reduce the dosage of opioids during the anesthesia maintenance phase.

Relación entre las ciencias básicas y clínicas en la modulación central del dolor / Relationship between basic and clinical sciences in central pain modulation

Esta revisión busca proporcionar a los profesionales de la salud una mayor comprensión del dolor para su actividad clínica-asistencial. Basados en la hipóte-sis de neuroplasticidad presentada inicialmente por Ramón y Cajal y la teoría de la compuerta en la vía dolorosa presentada por Melzack y Wall, se ha ela-borado una revisión bibliográfica con el objetivo de abordar la modulación de la vía nociceptiva desde un punto de vista fisiopatológico. Asimismo, se presen-tan los principales resultados obtenidos durante los últimos años en nuestro laboratorio usando ratas Wistar hembras como modelo de dolor experimental. Finalmente, se describe un circuito original de modu-lación central a nivel del subnúcleo caudal del trigé-mino con una visión integral de los componentes del sistema nociceptivo orofacial, para ayudar al clínico a comprender situaciones de sensibilización central con perpetuación del dolor y cómo paulatinamente el sistema nervioso central pone en marcha un sistema de modulación para adaptarse y alcanzar un estado similar al basal (AU)

This review aims to provide health professionals with a better understanding of pain for their clinical-care activity. Based on the neuroplasticity hypothesis initially presented by Ramón and Cajal, and the gate theory in the pain pathway presented by Melzack and Wall, a literature review has been carried out with the aim of addressing the modulation of the nociceptive pathway from a pathophysiological point of view. The main results obtained in recent years in our laboratory using female Wistar rats as an experimental pain model are also presented. Finally, an original central modulation circuit at the level of the caudal trigeminal subnucleus is described with a comprehensive view of the components of the orofacial nociceptive system, to help the clinician to understand situations of central sensitization with perpetuation of pain and how the central nervous system gradually sets in motion a modulation system to adapt and reach a state similar to the basal one (AU)

Bradykinin-induced nociceptive responses are more potent than capsaicin-induced responses in rat models

Background: Peripheral blood vessels are concerned with sensing the perivascular nociceptive information and signaling it to the higher centers through ipsilateral somatic nerves, thereby regulating the cardiorespiratory parameters by means of vasosensory reflex responses. Aims and Objectives: The present study was conducted to compare the potency of nociceptive responses elicited by bradykinin (BK) with the capsaicin-induced responses. Materials and Methods: Charles-Foster rats were anesthetized with urethane and injected intraperitoneally. After tracheostomy, the right femoral artery was cannulated with a 24G, double ported cannula for administering the chemicals/saline through vertical port and to record the blood pressure (BP) through horizontal port. BP, Electrocardiogram, and respiratory movements were recorded. Results: Injection of capsaicin into a segment of femoral artery evoked instantaneous transient tachypnoeic, hyperventilatory, and hypotensive responses. BK also produced similar pattern of nociceptive responses along with a transient fall in heart rate. In addition, the vasosensory responses produced by BK are of greater magnitude as compared to the capsaicin. Conclusions: BK is more potent in eliciting reflex nociceptive responses as compared to capsaicin. Further, BK has an additional cardioprotective role by slowing the heart, in the events of acute inflammation.

Extract of Glycyrrhiza glabra root attenuates nociception in experimental pain models: the role of BKCa channels / Extracto de raíz de Glycyrrhiza glabra atenúa la nocicepción en modelos experimentales de dolor: el rol de los canales BKCa

Abstract: The aim of this study was to evaluate the functional interaction of Glycyrrhiza glabra root extract (GGRE) on the large conductance Ca 2+ - activated K + (BKCa) channels expressed in the peripheral nervo us system by using nociception and inflammation models in rodents in vivo . Besides toxicity studies and open field tests, nociception and inflammation tests were performed on rodents. Different doses of GGRE were given orally to rats and mice. Naloxone, in domethacin, morphine, NS1619 and iberiotoxin (IbTX) were administered. GGRE had both anti - nociceptive and anti - inflammatory activity in rats and mice. GGRE exhibited an analgesic effect by decreasing the time - course of the pain threshold or reaction time i n some nociceptive tests. Furthermore, GGRE reduced level of pro - inflammatory cytokines, including TNF - α and IL - 1ß. As a conclusion, GGRE can alleviate the pain sensation of the afferent nerves and can reduce inflammation and associated pain by activating B KCa channels and reducing the levels of TNF - α, IL1ß

Resumen: El objetivo de este estudio fue evaluar la interacción funcional del extracto de raíz de Glycyrr hiza glabra (GGRE) en los canales de K + (BKCa) activados por Ca 2+ de gran conductancia expresados en el sistema nervioso periférico mediante el uso de modelos de nocicepción e inflamación en roedores in vivo . Además de los estudios de toxicidad y las prueb as de campo abierto, se realizaron pruebas de nocicepción e inflamación en roedores. Se administraron por vía oral diferentes dosis de GGRE a ratas y ratones. Se administraron naloxona, indometacina, morfina, NS1619 e iberiotoxina (IbTX). GGRE tenía activi dad tanto antinociceptiva como antiinflamatoria en ratas y ratones. GGRE mostró un efecto analgésico al disminuir la evolución temporal del umbral del dolor o el tiempo de reacción en algunas pruebas nociceptivas. Además, GGRE redujo el nivel de citocinas proinflamatorias, incluidas TNF - α e IL - 1ß. Como conclusión, GGRE puede aliviar la sensación de dolor de los nervios aferentes y puede reducir la inflamación y el dolor asociado activando los canales BKCa y reduciendo los niveles de TNF - α, IL1ß.

Exactitud diagnóstica del índice de nocicepción analgesia para la evaluación del dolor en pacientes críticos / Diagnostic accuracy of analgesia nociception index for pain assessment in critically ill patients / Precisão diagnóstica do índice de analgesia nocicepção para avaliação da dor em pacientes críticos

Resumen: La evaluación de la presencia de dolor en el enfermo sometido a sedación profunda y ventilación mecánica es posible a través de escalas que se basan en datos clínicos indirectos. El índice de nocicepción analgesia (ANI) es utilizado en enfermos anestesiados en la sala quirúrgica. La información sobre su eficacia en los enfermos críticos es escasa. Este trabajo prospectivo, observacional y analítico evalúa el rendimiento diagnóstico de ANI para detectar dolor en los enfermos críticos en ventilación mecánica, sedados con RASS de -3 a -1. Como estándar se utilizaron dos escalas clínicas (BPS y CPOT) aplicadas por médicos y enfermeras de manera simultánea a la medición de ANI, en cuatro ocasiones durante un periodo de 12 minutos. En 23 enfermos y 224 mediciones, la capacidad discriminativa medida a través de áreas por debajo de curvas ROC osciló entre 0.779 y 0.817. El puntaje de ANI con mejor capacidad diagnóstica osciló entre 52 y 55. Utilizando el valor umbral de 50, la sensibilidad osciló entre 0.418 y 0.524, la especificidad entre 0.910 y 0.980. Se reportan los valores predictivos y las razones de verosimilitud. Los cambios en ANI y las escalas, originados por procedimientos durante la medición, tuvieron una concordancia que osciló entre 28 y 41%. Los resultados identifican una tecnología con potencial para su utilización en el enfermo crítico. Son necesarios más estudios que corroboren nuestros resultados.

Abstract: The assessment of pain in patients undergoing deep sedation and mechanical ventilation is possible through scales that are based on indirect clinical data. The Analgesia Nociception Index (ANI) is used in anesthetized patients in the operating room. Information on its efficacy in critically ill patients is scarce. This prospective, observational and analytical study evaluates the diagnostic performance of ANI to detect pain in critically ill patients on mechanical ventilation and sedated (RASS from -3 to -1). Two clinical scales (BPS and CPOT) were used as standard, applied by doctors and nurses simultaneously to the ANI measurement, on four occasions during a 12-minute period. In 23 patients and 224 measurements, the discriminative capacity measured through ROC curve areas ranged between 0.779 and 0.817. The ANI score with the best diagnostic capacity ranged between 52 and 55. Using the threshold value of 50, the sensitivity ranged between 0.418 and 0.524, the specificity between 0.910 and 0.980. Predictive values and likelihood ratios are reported. The changes in ANI and the scales, originated by procedures during the measurement, had a concordance that ranged between 28 and 41%. The results identify a technology with potential for use in the critically ill. More studies are needed to corroborate our results.

Resumo: A avaliação da presença de dor em pacientes submetidos à sedação profunda e ventilação mecânica é possível por meio de escalas baseadas em dados clínicos indiretos. O índice de analgesia nocicepção (ANI) é utilizado em pacientes anestesiados na sala de cirurgia. As informações sobre sua eficácia em pacientes críticos são escassas. Este estudo prospectivo, observacional e analítico avalia o desempenho diagnóstico do ANI para detectar dor em pacientes críticos em ventilação mecânica, sedados com RASS de -3 a -1. Como padrão, foram utilizadas duas escalas clínicas (BPS e CPOT) aplicadas por médicos e enfermeiros simultaneamente à medida do ANI, em quatro ocasiões durante um período de 12 minutos. Em 23 pacientes e 224 medidas, a capacidade discriminativa medida através das áreas sob as curvas ROC variou entre 0.779 e 0.817. O escore ANI com melhor capacidade diagnóstica variou entre 52 e 55. Utilizando o valor limite de 50, a sensibilidade variou entre 0.418 e 0.524, a especificidade entre 0.910 e 0.980. Relatam-se valores preditivos e razões de verossimilhança. As alterações no ANI e nas escalas, causadas por procedimentos durante a medição, tiveram uma concordância que variou entre 28 e 41%. Os resultados identificam uma tecnologia com potencial para uso em pacientes críticos. Mais estudos são necessários para corroborar nossos resultados.

Efeitos da fotobiomodulação na atividade de nociceptores e na expressão de citocinas pró-inflamatórias após lesão do disco da articulação temporomandibular em ratos / Effects of Photobiomodulation on nociceptive activity and in the expression of inflammatory citokynes after injury of the Temporomandibular Joint disc after in rats

A dor na articulação temporomandibular (ATM) é comum na clínica, na forma de artralgia. Geralmente, é devido a distúrbios do disco articular, deslocamentos ou trauma. Nosso objetivo foi analisar os efeitos da fotobiomodulação (PBM) na atividade nociceptora e na expressão de substâncias pró-inflamatórias no disco da ATM após lesão unilateral em ratos. Foi realizada lesão no disco após acesso cirúrgico na ATM sob anestesia geral. 40 ratos foram divididos em 4 grupos (n = 10 cada): Grupo Op + PBM: Lesão cirúrgica do disco articular e PBM; Grupo SHAM: Falso operado +PBM; Grupo Op: lesão cirúrgica do disco articular; Grupo Naive: controle. Dez sessões foram realizadas com laser GaAs com comprimento de onda de 904 nm e densidade de energia 6J / cm2. Uma parte das amostras contendo tecidos moles articulares foram preparadas para determinação do conteúdo protéico por espectrofotometria da substância P (SP), receptor do potencial transiente vaniloide do subtipo-1 (TRPV-1) e peptídeo relacionado ao gene da calcitonina (CGRP), Interleucina 6 (IL-6), Interleucina 1 beta (IL1-) e Fator de Necrose Tumoral alfa (TNF-). Foi realizada análise de variância de duas vias com pós-teste de Tukey (p <0,050). Outra parte foi utilizada para análise histológica e histomorfometrica. Houve aumento da expressão das substâncias avaliadas após lesão e uma diminuição significante após PBM, quando comparado com os demais grupos. A análise histológica e histomorfométrica mostrou reparação com melhor organização tecidual no grupo Op + PBM O uso da PBM é eficaz na modulação da atividade nociceptora e nas expressões das citocinas pró-inflamatórias na ATM.

Pain in the temporomandibular joint (TMJ) is common in the clinic, in the form of arthralgia. It is usually due to joint disc disorders, dislocations, or trauma. Our objective was to analyze the effects of photobiomodulation (PBM) on nociceptor activity and on the expression of pro-inflammatory substances in the TMJ disc after unilateral injury in rats. Disc injury was performed after surgical access to the TMJ under general anesthesia. 40 rats were divided into 4 groups (n = 10 each): Group Op + PBM: Surgical lesion of the articular disc and PBM; SHAM group: False operated +PBM; Group Op: surgical lesion of the articular disk; Naive group: control. Ten sessions were performed with a GaAs laser with a wavelength of 904 nm and an energy density of 6J/cm2. A portion of the samples containing joint soft tissues were prepared for determination of protein content by spectrophotometry of substance P (SP), receptor transient vanilloid potential subtype-1 (TRPV-1) and calcitonin gene-related peptide (CGRP), Interleukin 6 (IL-6), Interleukin 1 beta (IL1-) and Tumor Necrosis Factor alpha (TNF-). Two-way analysis of variance with Tukey's post-test (p<0.050) was performed. Another part was used for histological and histomorphometric analysis. There was an increase in the expression of the evaluated substances after injury and a significant decrease after PBM, when compared to the other groups. Histological and histomorphometric analysis showed repair with better tissue organization in the Op + PBM group the use of PBM is effective in modulating nociceptor activity and expressions of pro-inflammatory cytokines in the TMJ.

Sistema endocannabinoide y cannabidiol en el manejo del dolor en perros: revisión narrativa

Introducción: la marihuana (Cannabis sativa L.) es una planta originaria de Asia cada vez más reconocida por su valor terapéutico en la medicina humana y veterinaria. Contiene una gran cantidad de componentes entre los que destacan los fitocannabinoides, de los cuales los más representativos son el delta-9-tetrahidrocannabinol (THC) y Cannabidiol (CBD) que se acoplan respectivamente a los receptores CB1 y CB2 en el sistema endocannabinoide que es un sistema neurotransmisor entre células que regula varios procesos en los vertebrados como memoria, dolor, inflamación, apetito y procesos inmunológicos entre otros. Objetivo: realizar una síntesis narrativa del sistema endocannabinoide y cannabidiol en el manejo del dolor en perros, a partir de la búsqueda de publicaciones en bases de datos electrónica PubMed, NCBI, SciELO, Science Direct, Dialnet, Google y Google Académico. Resultados: el CBD es el principal cannabinoide utilizado en la terapia del manejo del dolor en perros por sus propiedades analgésicas y carencia de efectos psicoactivos. Conclusión: se evidencia la necesidad de realizar más investigaciones con ensayos clínicos controlados sobre el uso terapéutico del cannabidiol, que tengan validez interna y externa, con poblaciones más significativas en la especie de interés.

SUMMARY Introduction: marijuana (CannabissativaL.) is a plant native to Asia that is increasingly recognized for its therapeutic value in human and veterinary medicine. It contains a large number of components among which the phytocannabinoids stand out, of which the most representative are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) that are coupled respectively to the CB1 and CB2 receptors in the endocannabinoid system, which is a neurotransmitter system between cells that regulates various processes in vertebrates such as memory, pain, inflammation, appetite and immune processes among others. Aim: to carry out a narrative synthesis of the endocannabinoid and cannabidiol system in the management of pain in dogs, from the search of publications in electronic databases PubMed, NCBI, SciELO, Science Direct, Dialnet, Google and Google Scholar. Results: CBD is the main cannabinoid used in pain management therapy in dogs due to its analgesic proper-ties and lack of psychoactive effects. Conclusion: there is evidence of the need for more research with controlled clinical trials on the therapeutic use of cannabidiol, which have internal and external validity, with more significant populations in the species of interest.

Introdução: a maconha (Cannabis sativa L.) é uma planta nativa da Ásia que é cada vez mais reconhecida por seu valor terapêutico na medicina humana e veterinária. Ele contém muitos componentes entre os quais se destacam os fitocanabinóides, dos quais os mais representativos são delta-9-tetrahidrocanabinol (THC) e Canabidiol (CBD) que estão acoplados respectivamente aos receptores CB1 e CB2 no sistema endocanabinóide, que é um sistema neurotransmissor entre as células que regula vários processos nos vertebrados, como memória, dor, inflamação, apetite e processos imunológicos, entre outros. Objetivo: realizar uma síntese narrativa do sistema endocanabinoide e canabidiol no manejo da dor em cães, a partir da busca de publicações nas bases de dados eletrônicas PubMed, NCBI, SciELO, Science Direct, Dialnet, Google e Google Scholar. Resultados: O CBD é o principal canabinoide utilizado na terapia de controle da dor em cães devido às suas propriedades analgésicas e ausência de efeitos psicoativos. Conclusão: há evidências da necessidade de mais pesquisas com ensaios clínicos controlados sobre o uso terapêutico do canabidiol, que tenham validade interna e externa, com populações mais significativas nas espécies de interesse.

La relevancia moral del dolor de animales de experimentación y de producción / The moral relevance of pain in experimental and production animals

RESUMEN: El aspecto emocional del dolor no solo es controvertido en aves, peces y roedores, sino también en los seres humanos autoconscientes. Cuando el dolor emocional, o la insatisfacción, es vista como un mal intrínseco, evitarla o, al menos, minimizarla es un deber moral directo. El objetivo de este artículo es mostrar que no solo los modelos animales mamíferos que se utilizan en experimentación -rata (Rattus norvegicus) y ratón (Mus musculus)- sienten dolor, como reconocen universalmente las instituciones que se ocupan del bienestar animal, sino también los peces de laboratorio (Danio rerio) y los de producción (Salmo salar), y que este hecho es moralmente relevante desde el punto de vista de todas las concepciones de la moral que suelen enfrentarse en los debates morales públicos y académicos. En consecuencia, también en el caso de los peces habría que tener en cuenta indicadores de bienestar animal.

SUMMARY: The emotional aspect of pain is not only controversial in fish and rodents, but also in self-conscious humans. When pain or dissatisfaction is seen as an intrinsic evil, avoiding it or at least minimizing it is a moral duty direct. The objective of this article is to refer to pain, stress and the most widely used indices of animal welfare both in laboratory fish (Danio rerio) and production fish (Salmo salar) as well as in rat experimental animal models (Rattus norvegicus) and mouse (Mus musculus).

Impact of sex and environmental conditions on the responses to pain in zebrafish / Impacto do sexo e das condições ambientais nas respostas do peixe-zebra à dor

ABSTRACT BACKGROUND AND OBJECTIVES: Adult zebrafish (Danio rerio) has been proposed as a low-cost and simple alternative to the use of rodents in laboratory research on novel compounds with antinociceptive potential. This study aimed to assess whether there is an influence of animal sex and the test environment on the orofacial nociceptive behavior of the adult zebrafish. METHODS: First, cinnamaldehyde, menthol, capsaicin, acidic saline, or glutamate was applied into the lips of the adult male or female zebrafish. Naive groups were included as control. The orofacial nociception was quantified in terms of locomotor activity. In other series of experiments, it was evaluated whether the apparatus, acclimatization, period of test, temperature of the water and color of the open field would alter the nociceptive response to cinnamaldehyde. RESULTS: The nociceptive behavior did not depend on the sex of the animal, apparatus, time the test was performed or the color of the open field. However, acclimatization promoted nociceptive behavior in naive animals and did not alter the nociceptive response to cinnamaldehyde (p<0.01 vs acclimatized naive). The nociception behavior was presented only when the test was performed at a temperature of 26ºC (p<0.01 vs naive). CONCLUSION: The results suggest the need to control the environment and water temperature as an environmental source of variation during the nociceptive behavior test of the adult zebrafish.

RESUMO JUSTIFICATIVA E OBJETIVOS: O peixe-zebra adulto (Danio rerio) tem sido proposto como uma alternativa simples e de baixo custo ao uso de roedores em pesquisas laboratoriais de novos compostos com potencial antinociceptivo. Este estudo teve como objetivo avaliar se há influência do sexo do animal e do ambiente de teste no comportamento nociceptivo orofacial do peixe-zebra adulto. MÉTODOS: Inicialmente, cinamaldeído, mentol, capsaicina, solução salina ácida ou glutamato foi aplicada nos lábios do peixe-zebra adulto masculino ou feminino. Grupos naive foram incluídos como controle. A nocicepção orofacial foi quantificada em termos de atividade locomotora. Em outra série de experimentos, foi avaliado se o aparato, aclimatação, período de teste, temperatura da água e cor do campo aberto alterariam a resposta nociceptiva ao cinamaldeído. RESULTADOS: O comportamento nociceptivo não dependeu do sexo do animal, do equipamento de teste, do horário em que o teste foi realizado ou da cor do campo aberto. No entanto, a aclimatação promoveu comportamento nociceptivo em animais naive e não alterou promoveu comportamento nociceptivo em animais naive e não alterou a resposta nociceptiva ao cinamaldeído (p<0,01 vs naive aclimatado). O comportamento nociceptivo foi verificado apenas quando o teste foi executado a uma temperatura de 26ºC (p<0,01 vs naive). CONCLUSÃO: Os resultados sugerem a necessidade de controlar o ambiente e a temperatura da água como fonte de variação ambiental durante o teste de comportamento nociceptivo do peixe-zebra adulto.

KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice / 神经科学通报·英文版

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

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.

Estimación del dolor durante el perioperatorio: Una revisión narrativa de los dispositivos disponibles / Estimative pain measurement during perioperative period: a review of current available devices

Pain is a complex subjective organic function which is influenced by sensorial, emotional, cognitive and behavioral elements. Despite the wide offer of pain measurement devices in the perioperative period, none of them is completely validated for their transverse use in the anesthetic practice. The aim of this review is to present the existing devices for objective pain evaluation during the perioperative period along with the scientific evidence supporting each of them. Articles from the PubMed/MEDLINE literature search engine were reviewed. As result, 37 articles were selected due to its relevance, from which 13 pain assessment devices were described, regarding its clinical relevance as well as the amount of scientific evidence found. Among them are ANI, NOL, pupillometry, qNOX, and others. The nociceptive measurement performed by most of these is based mainly on the evaluation of the autonomic nervous system activity and variations of the electroencephalographic signal. However, it is not possible to recommend any particular device. This review aims to offer a broad overview of the available options in order to estimate the role that each of them could play in clinical anesthesiology practice.

El dolor es una experiencia subjetiva compleja en la que inciden elementos sensoriales, emocionales, cognitivos y conductua- les. A pesar de una amplia oferta de dispositivos para medir dolor en el perioperatorio, hoy no existe un instrumento de medición de analgesia validado y utilizado transversalmente en la práctica anestésica. El objetivo de esta revisión es presentar las actuales opciones disponibles para la medición del dolor agudo utilizadas en el período perioperatorio junto con la evidencia científica que respalda cada una de ellas. Se realizó una revisión de la literatura utilizando como fuente de búsqueda bibliográfica la base de datos MEDLINE/pubMed utilizando términos MESH. Como resultado, se seleccionaron 37 artículos de acuerdo a su importancia, a partir de los cuales se describen 13 dispositivos de valoración nociceptiva, a propósito de su relevancia clínica como también por la cantidad de evidencia científica encontrada. Entre ellos destacan ANI, NOL, pupilometría, qNOX, entre otros. La medición nociceptiva realizada por la mayoría de estos se basa principalmente en la evaluación de la actividad del sistema nervioso autónomo y variaciones de la señal electroencefalográfica. Sin embargo, no es posible recomendar algún dispositivo en particular. Esta revisión pretende ofrecer una visión amplia de las opciones disponibles con el fin de estimar el rol que cada uno de ellos podría desempeñar en la práctica clínica anestesiológica.

O modelo de dor inflamatória induzida pela carragenina como estratégia para avaliar a ação de drogas sobre a dor miofascial / The carrageenan-induced inflammatory pain model as a tool to assess the action of drugs on myofascial pain

A dor miofascial orofacial vem sendo tratada com analgésicos, anti-inflamatórios, relaxantes musculares, fisioterapia, laserterapia e placas oclusais. Contudo, muitas vezes, tais condutas falham em amenizar o quadro doloroso, havendo a necessidade de testar outras estratégias de tratamento. Metodologia: Uma opção para avaliação experimental dessas terapias seria o teste de dor induzido pela carragenina, associado ao teste de avaliação do limiar nociceptivo, originalmente desenvolvido para avaliar a ação de drogas nas patas de roedores. Sendo assim, o presente estudo analisou a nocicepção causada pela carragenina em masseteres de ratos, através do teste de Von Frey, correlacionando-a com alterações teciduais produzidas por esta droga. A carragenina foi injetada no músculo masseter de ratos, enquanto o grupo controle recebeu soro fisiológico. O limiar nociceptivo foi mensurado com um analgesímetro digital antes da administração da carragenina e 5 horas, 1, 3 e 7 dias após o seu uso. Decorridos 8 dias da intervenção, os animais foram eutanasiados, sendo seus masseteres encaminhados para processamento histológico e coloração H&E. Resultados: Observou-se uma diminuição do limiar da resposta nociceptiva em todos os períodos no grupo com carragenina, quando comparado com o grupo controle, havendo diferença estatisticamente significante nas 5 horas. A análise histológica do grupo experimental mostrou a presença de espaços perimisial e endomisial alargados e preenchidos por uma matriz com alguns linfócitos, muitos macrófagos e raros mastócitos. Conclusão: Os resultados indicaram que a associação de uma droga inflamatória com o método Von Frey pode ser uma opção para o estudo do efeito de terapias de dor miofascial.

Myofascial orofacial pain has been treated with analgesics, anti-inflammatories, muscle relaxants, physiotherapy, laser therapy and occlusal plaques. However, many times, such behaviors fail to alleviate the painful condition, with the need to test other treatment strategies. Methodology: An option for experimental evaluation of these therapies would be the pain test induced by carrageenan associated with the nociceptive threshold assessment test, originally developed to assess the action of drugs on the rodents' feet. Thus, the present study analyzed the nociception caused by carrageenan in rat masseter using the Von Frey test, correlating it with tissue changes produced by this drug. Carrageenan was injected into the masseter muscle of rats, while the control group received saline. The nociceptive threshold was measured with a digital analgesometer before administration of carrageenan and 5 hours, 1, 3 and 7 days after its use. After 8 days of the intervention, the animals were euthanized, and their masseters were sent for histological processing and H&E staining. Results: There was a decrease in the nociceptive response threshold in all periods in the group treated with carrageenan when compared to the control group, with a statistically significant difference at 5 hours. Histological analysis of the experimental group showed the presence of enlarged perimisial and endomisial spaces, filled by a matrix with some lymphocytes, many macrophages and rare mast cells. Conclusion: Results indicated that the association of an inflammatory drug with the Von Frey method may be an option for studying the effect of therapies on myofascial pain.

Guiding opioid-free intravenous antinociception with the Analgesia Nociception Index: a case report / Antinocicepção intravenosa sem opioides orientada pelo Índice de Analgesia/Nocicepção: relato de caso

Abstract Background: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. Case report: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. Conclusion: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.

Resumo Introdução A anestesia sem opioides diminui a incidência de eventos adversos associados aos opioides, mas a profundidade antinociceptiva ideal dessa abordagem não está claramente definida. Personalizar a infusão intraoperatória sem opioides com o uso de monitor de nocicepção pode ser a solução. Relato de caso Descrevemos a viabilidade e as eventuais limitações da titulação da antinocicepção sem opioides por meio do uso do Índice de Analgesia/Nocicepção (Mdoloris, Lille, França) durante cirurgia abdominal de grande porte em paciente com obesidade. Depois de estabilizar o equilíbrio nocicepção-antinocicepção da paciente no intraoperatório, revertemos rapidamente a anestesia e a paciente não precisou de opioides no pós-operatório. Conclusão A personalização da antinocicepção sem opioides por meio do emprego de monitor de nocicepção é factível. A abordagem pode otimizar a antinocicepção intraoperatória e melhorar o conforto pós-operatório.

Dolor en Aves y Peces / Pain in Birds and Fish

Se ha demostrado que aves y peces presentan estructuras anatómicas similares a las que transducen el dolor en humanos y, además, muestran respuestas negativas frente a estímulos nocivos, junto a cambios conductuales. De acuerdo con esto, existe una responsabilidad moral frente al uso de estos animales en investigación para evitar y/o minimizar el dolor.

Birds and fish have been shown to present anatomical structures similar to those that transduce pain in humans, and also show negative responses to harmful stimuli, along with behavioural changes. There is a moral responsibility regarding the use of these animals in research to avoid and/or minimize pain. In this review we compare the pain-related morphology of birds and fish, using pain in humans as a starting point.

Neuronas participantes en la modalidad sensorial del dolor bucofacial de la periferia hasta el encéfalo / Neurons involved in the sensory modality of orofacial pain from periphery to encephalon

Introducción: El dolor proveniente de cabeza y cuello se vincula a la vía trigeminal, y participan tres neuronas: neurona de primer orden ubicada en ganglio trigeminal; neurona de segundo orden, en el subnúcleo caudal del nervio trigémino; y la neurona de tercer orden que parte de la zona medial del complejo ventrobasal de tálamo y termina en la corteza cerebral. Objetivo: Interpretar que el daño tisular, mediante impulsos nerviosos es transmitido por una cadena de neuronas hasta el encéfalo. Contenido: Las neuronas de primer orden, sus cuerpos neuronales se encuentran ubicados en el ganglio espinal del trigémino, en hueso temporal. En el subnúcleo caudal, se ubican las neuronas de segundo orden que reciben estímulos nociceptivos y de temperatura de la cara y la boca; sus axones se cruzan en la extensión de este subnúcleo, y ascienden contralateralmente, y establecen sinapsis en el tálamo con neuronas de tercer orden. En el encéfalo no hay un único "centro del dolor", las neuronas de tercer orden, terminan en diferentes áreas de la corteza cerebral que se reconocen como "matriz del dolor". Consideraciones finales: Tres conjuntos de neuronas conforman la vía nociceptiva trigeminal, la primera ubicada en el ganglio trigeminal fuera del sistema nervioso central y los otros dos conjuntos neuronales conforman núcleos dentro del mismo(AU)

Introduction: Pain from the head and neck is linked to the trigeminal pathway and three neurons participate: a first-order neuron located in the trigeminal ganglion, a second-order neuron from the subnucleus caudalis of the trigeminal nerve, and a third-order neuron which starts from the medial area of the ventrobasal thalamus complex and ends in the cerebral cortex. Objective: Describe the way in which a chain of neurons transmit tissue damage to the encephalon by means of nerve impulses. Content: In first-order neurons, their neuronal bodies are located in the trigeminal spinal ganglion, in temporal bone. In the subnucleus caudalis, second-order neurons are found which receive nociceptive and temperature stimuli from the face and mouth. Their axons cross over the extension of this subnucleus, ascend contralaterally and establish synapses with third-order neurons in the thalamus. In the encephalon there is not a single "pain center": third-order neurons end in different areas of the cerebral cortex recognized as the "pain matrix". Final considerations: Three sets of neurons make up the trigeminal nociceptive pathway. The first one is located in the trigeminal ganglion outside the central nervous system whereas the other two form nuclei within it(AU)

Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

Background DPP-4 inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day 1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to receive other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) was monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated modest analgesic activity compared to baseline and placebo. Its role in painful diabetic conditions may be further explored.