Dualismo, modulación alostérica y señalización diferencial en los receptores opiáceos: futuro potencial terapéutico / Dualism, allosteric modulation and biased signaling of opioid receptors: Future therapeutic potential

Los fármacos opioides permanecen como fármacos de elección en el tratamiento del dolor agudo postoperatorio y del dolor crónico oncológico. Su prescripción inadecuada, ha dado lugar, en algunos países, a una verdadera «crisis de opioides». En este contexto, puede resultar interesante el potencial terapéutico de algunos ligandos que actúan como moduladores alostéricos de la fijación de los agonistas opioides y su capacidad de modular su actividad, modificando su afinidad, potencia e incluso eficacia. (AU)

Opioids are still the drugs of choice for the treatment of acute post-surgical pain and chronic cancer pain. Overprescribing of these drugs has given rise to an “opioid crisis” in some countries. In this context, attention has been drawn to the therapeutic potential of various ligands that act as allosteric modulators of orthosteric binding sites and modulate the drug's activity, affinity, potency, and even efficacy. (AU)

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA.

OBJECTIVES: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. METHODS: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. RESULTS: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. CONCLUSION: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.

Dualism, allosteric modulation, and biased signaling of opioid receptors: Future therapeutic potential.

Opioids are still the drugs of choice for the treatment of acute post-surgical pain and chronic cancer pain. Overprescribing of these drugs has given rise to an "opioid crisis" in some countries. In this context, attention has been drawn to the therapeutic potential of various ligands that act as allosteric modulators of orthosteric binding sites and modulate the drug's activity, affinity, potency, and even efficacy.

[Methods of analgesia and euthanasia in backyard poultry]. / Methoden der Analgesie und Euthanasie in der Hobby-Hühnerhaltung.

INTRODUCTION: The keeping of chickens in the backyard is growing in popularity in urban and suburban areas, numbers of animals are increasing and as a result small animal practitioners are more and more frequently faced with chickens as patient. Clinical conditions in backyard poultry often require the treatment of pain. The challenges regarding the adequate use of analgesics include: 1. Recognition and assessment of pain, which necessitates good knowledge of chicken behaviour, 2. Selection of the adequate drug and dosage based on evidence that is often not available for chickens, but spread over different species of birds, and 3. Implementation of food safety regulations, which result from the dual use of backyard poultry as «food producing pets¼. Analgesics used in chickens include opiates, nonsteroidal anti-inflammatory drugs and local analgesics. The opiate butorphanol has been shown to have an analgesic effect of approximately two hours in chickens. Tramadol and methadone show some promise as analgesics, but more evidence is needed especially regarding bioavailability. The nonsteroidal anti-inflammatory drugs meloxicam and carprofen appear to have an analgesic effect. Variable metabolism between breeds of chickens and the risk of accumulation, especially when used for periods exceeding five consecutive days, need to be taken into account regarding dosage. Lidocaine and bupivacaine have successfully been used in chickens for nerve blocks and spinal anaesthesia and should be included as part of multimodal analgesia especially during surgery. In cases, where termination of life is necessary the preferred method consists of an injectable anaesthesia followed by intravenous application of a barbiturate.

INTRODUCTION: L'élevage de volailles de basse-cour est de plus en plus populaire dans les zones urbaines et suburbaines, le nombre d'animaux augmente et les praticiens pour petits animaux sont, par conséquent, de plus en plus souvent confrontés à ces animaux en tant que patients. Les conditions cliniques des volailles de basse-cour nécessitent souvent le traitement de la douleur. Les défis liés à l'utilisation adéquate des analgésiques sont les suivants 1. La reconnaissance et l'évaluation de la douleur, qui nécessitent une bonne connaissance du comportement des volailles, 2. la sélection du médicament et du dosage adéquats sur la base de preuves qui ne sont souvent pas disponibles pour les volailles mais sont réparties entre différentes espèces d'oiseaux, et 3. la mise en œuvre des réglementations en matière de sécurité alimentaire, qui résultent de la double utilisation des volailles de basse-cour en tant qu'«animaux de compagnie producteurs de denrées alimentaires¼. Les analgésiques utilisés chez les poulets comprennent les opiacés, les anti-inflammatoires non stéroïdiens et les analgésiques locaux. Il a été démontré que l'opiacé butorphanol a un effet analgésique chez les poulets, d'une durée d'environ deux heures. Le Tramadol et la méthadone sont des analgésiques prometteurs, mais des preuves supplémentaires sont nécessaires, notamment en ce qui concerne leur biodisponibilité. Les anti-inflammatoires non stéroïdiens Meloxicam et Carprofen semblent avoir un effet analgésique. En ce qui concerne la posologie, il convient de tenir compte du métabolisme variable selon les races de poules et du risque d'accumulation, en particulier en cas d'utilisation pendant des périodes supérieures à cinq jours consécutifs. La lidocaïne et la bupivacaïne ont été utilisées avec succès chez les poules pour les blocs nerveux ainsi que pour l'anesthésie spinale et devraient être incluses dans l'analgésie multimodale, en particulier pendant la chirurgie. Dans les cas où il est nécessaire de mettre fin à la vie de l'animal, la méthode de choix consiste en une anesthésie injectable suivie d'une application intraveineuse d'un barbiturique.

Uso de opioides en pacientes con enfermedad crónica avanzada en situación de últimos días / Use of opioids in patients with advanced chronic disease in the last days of life

Objetivo: Conocer el uso de opioides en el paciente con enfermedad crónica avanzada en los últimos días de vida. Métodos: Estudio retrospectivo, multicéntrico, descriptivo y analítico. Se recogieron datos de los servicios de Geriatría del Hospital Universitario La Paz, Medicina Interna del Complejo Hospitalario de Toledo, Unidad de Hospital a Domicilio del Hospital Marina Baixa de la Vila Joiosa y del Hospital Centro de Cuidados Laguna. Se incluyeron en el estudio los pacientes ingresados con enfermedad avanzada no oncológica fallecidos entre el 1 de marzo de 2019 y el 29 de febrero de 2020. Se estudiaron distintas variables: edad, sexo, enfermedad principal, motivo de ingreso, valoración por cuidados paliativos, uso previo de opioides, uso de opioides en situación de últimos días, opioide, dosis, vías de administración e indicación. Resultados: En el estudio se incluyeron 261 pacientes, 143 (55 %) mujeres y 118 (45 %) hombres, con una edad media de 84 años. La enfermedad principal más frecuente fue la demencia, seguido de insuficiencia cardiaca y patología respiratoria. El motivo de ingreso más frecuente fue deterioro debido a la enfermedad de base seguido de infección respiratoria y sepsis. En la situación de últimos días, la mayoría de los pacientes tenían pauta de opioide basal (94 % morfina) y de rescate (98 % morfina). La vía de administración más utilizada fue la subcutánea (98 %) y la indicación más frecuente fue la disnea (42 %). La mediana de dosis equivalente de morfina oral diaria por enfermedad principal y por motivo de ingreso fue de 30 mg/día. Conclusiones: El uso de opioides en las enfermedades crónicas avanzadas en situación de últimos días está ampliamente extendido. La morfina es el opioide más usado, independientemente de la enfermedad. La vía de administración más utilizada es la subcutánea. No encontramos diferencias entre pacientes con diferentes patologías. (AU)

Objective: To determine the use of opioids in patients with advanced chronic disease in the last days of life. Methods: A retrospective, multicenter, descriptive, analytical study. Data were collected from the Geriatrics Department of Hospital La Paz, Internal Medicine Department of Complejo Hospitalario de Toledo, Hospital at Home Unit of Hospital Marina Baixa in0 La Vila Joiosa, and Hospital Centro de Cuidados Laguna. The study included patients with advanced non-oncological disease who died between 1 March 2019 and 29 February 2020. Different variables were studied: age, sex, main disease, reason for admission, palliative care assessment, previous opioid use, opioid use in last days, opioid, dose, routes of administration, and indication. Results: The study included 261 patients, 143 (55 %) women and 118 (45 %) men, with a mean age of 84 years. The most frequent main disease was dementia, followed by heart failure and respiratory pathology. The most frequent reason for admission was deterioration due to the underlying disease followed by respiratory infection and sepsis. In the last-day situation, most patients had a baseline (94 % morphine) and rescue (98 % morphine) opioid regimen. The most common route of administration was subcutaneous (98 %) and the most common indication was dyspnea (42 %). The median daily oral morphine equivalent dose per main disease and reason for admission was 30 mg/day. Conclusions: The use of opioids in advanced chronic illness in the last days situation is widespread. Morphine is the most commonly used opioid regardless of disease. The most used route of administration is subcutaneous. We found no differences between patients with different pathologies. (AU)

Reducción del riesgo de constipación asociada a opioides con el uso de oxicodona/naloxona: metanálisis / Use of oxycodone/naloxone for reducing opioid-induced constipation risk: a meta-analysis

Introducción: Existe una relación directa entre el uso de opioides y la constipación, que afecta la calidad de vida de los pacientes y genera sobrecostes económicos al sistema de salud, pero opciones como la oxicodona/naloxona parecen reducir la incidencia de este efecto adverso. Métodos: Revisión sistemática y metanálisis en el escenario no oncológico, oncológico y postquirúrgico. A partir de una búsqueda en las siguientes bases de datos: PubMed, Embase, Web of Science, The Cochrane Library, Google Scholar y Open Grey, se incluyeron ensayos clínicos controlados aleatorizados con o sin comparador en población mayor de 18 años, sin límite en el tiempo de búsqueda en manuscritos con idioma en español o inglés. La evaluación de los sesgos de los estudios incluidos se realizó con la herramienta de Cochrane y para la evaluación de los efectos de las intervenciones se seleccionaron las diferencias de medias, con un modelo de efectos aleatorios. La heterogeneidad se realizó a partir del modelo de DerSimonian y Laird. Análisis de heterogeneidad y homogeneidad con la prueba Q de Cochrane que se suplementa con el estadístico I2. Resultados: Se incluyeron 18 ensayos clínicos (5934 pacientes). En la población con dolor no oncológico hubo una reducción del Bowel Function Index (BFI) en 15,84 puntos (IC 95 % −22,11 a −9,57), así como en los pacientes con dolor posquirúrgico, con reducción media de la puntuación de BFI de 9 puntos IC 95 % (−16,8 a −1,2); en el grupo de pacientes con dolor oncológico no se evidenció reducción en BFI, sino un leve aumento de 2,09 puntos (IC 95 % −5,99 a 10,17). Discusión: Se evidencian limitaciones en el soporte bibliográfico y nivel de evidencia para poder establecer recomendaciones respecto a su uso. Conclusión: La combinación oxicodona/naloxona presenta una reducción en la incidencia de constipación sin generar un impacto negativo en la calidad analgésica. (AU)

Background: There is a direct relationship between use of opioids and constipation, which affects the quality of life of patients and generates additional economic costs for the health system; but options such as oxycodone/naloxone appear to reduce the incidence of this adverse effect. Methods: On this basis, a meta-analysis was conducted in non-oncologic, oncologic, and postsurgical pain populations. It was based on a search in the following databases: PubMed, Embase, Web of Science, The Cochrane Library, Google Scholar and Open Grey, which included randomized controlled clinical trials with or without a control group, in a population older than 18 years, without any specific time frame in publication date; publications in Spanish or English were included. A bias risk assessment of the included studies was performed with the Cochrane tool; for evaluation of the effect of the intervention across different studies, mean differences were selected, with a random effects model. Heterogeneity variance was estimated with the DerSimonian and Laird method. Heterogeneity and homogeneity were measured with Cochran-Q complemented with I2 statistics.Results: Eighteen randomized clinical trials (5,934 patients) were included. In the population with non-oncologic pain, there was a reduction of the Bowel Function Index (BFI) by 15.84 points, 95 % CI (−22.11 to −9.57), as well as in the patients with post-surgical pain, with a mean reduction of the BFI score of 9 points, 95 % CI (−16.8 to −1.2); in the group of patients with oncologic pain no reduction in BFI was evidenced; instead there was a slight increase of 2.09 points, 95 % CI (−5.99 to 10.17). Discussion: There are limitations with the currently available literature and level of evidence to establish firm recommendations regarding their use. Conclusion: The oxycodone/naloxone combination presents a reduction in the incidence of constipation without generating a negative impact on analgesic quality. (AU)

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Etiopatogenia del prurito asociado a la enfermedad renal crónica: recomponiendo las piezas del puzle / Etiopathogenesis of chronic kidney disease-associated pruritus: Putting the pieces of the puzzle together

Definido como la sensación desagradable que provoca el deseo de rascarse, el prurito es el síntoma cutáneo más frecuente asociado a la uremia, pudiendo aparecer en casi la mitad de los pacientes con enfermedad renal crónica (ERC) avanzada. Más allá de su repercusión directa sobre la calidad de vida, el prurito asociado a la ERC (Pa-ERC) es un predictor independiente de mortalidad que además ejerce un efecto sinérgico con otros síntomas también relacionados con la calidad de vida, como la depresión y el insomnio. Aunque se han propuesto diferentes mecanismos para explicar su origen, la etiopatogenia del Pa-ERC sigue sin conocerse por completo. Dado que se han identificado nuevas dianas terapéuticas y recientemente varios ensayos clínicos han mostrado resultados prometedores, nuestra comprensión actual de las interrelaciones se ha ampliado significativamente, considerando multifactoriales los mecanismos fisiopatológicos subyacentes al Pa-ERC. En la presente revisión se discuten los potenciales factores desencadenantes de prurito en el paciente con ERC, incluyendo las hipótesis sobre la xerosis cutánea, el acúmulo de toxinas urémicas, la desregulación del sistema inmune y la inflamación sistémica, la neuropatía urémica y los desequilibrios en el sistema opioide endógeno, así como otras causas no urémicas de prurito, con el objetivo de orientar al clínico para realizar un adecuado abordaje etiopatogénico del Pa-ERC en su día a día. (AU)

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate etiopathogenic approach to CKD-aP in their day-to-day clinical practice. (AU)

Association of S(+) ketamine, dexmedetomidine and butorphanol for chemical restraint in scarlet macaws (Ara macao) / Associação cetamina S(+), dexmedetomidina e butorfanol na contenção química de araracangas (Ara macao)

The present study aimed at assessing the effects of combining 20 mg/kg S(+) ketamine with 25 µg/kg dexmedetomidine and 0.4 mg/kg butorphanol on the physiological parameters and anesthetic recovery time and score of eight captive scarlet macaw (Ara macao) specimens. These specimens were captured at the Marabá Zoobotanic Foundation (Fundação Zoobotânica de Marabá), Pará, using butterfly and mist nets, and subsequently subjected to the proposed protocol. The following physiological parameters were evaluated: heart rate (HR), respiratory rate (RR), saturation of peripheral oxygen (SpO2), body temperature (BT), and non-invasive blood pressure 5 min after drug administration (M0) and every 10 min thereafter (M1‒M5), with a total of 55 min of analysis of anesthetic effects. Glycemia was measured 5 min after drug administration and every 30 min thereafter. Anesthetic induction and recovery times were also determined. Among the parameters evaluated in this study, both HR and BT significantly decreased throughout the anesthetic period, with the lowest levels at 55 min after drug administration (M5). In contrast, RR did not significantly differ, and all animals remained stable, maintaining an RR close to a mean of 20 ± 8 cpm. Throughout the anesthetic period, SpO2was 92 ± 5%, with no significant difference. The birds remained under spontaneous ventilation and without oxygen supplementation. Systolic, diastolic, and mean blood pressures remained stable, with no significant differences in any of these measurements. At M0 and M3, the glycemia decreased slightly, albeit with no significant difference justifying an adverse effect or even hypoglycemia. The anesthetic induction time, from M0 to decubitus, was 2.4 ± 0.7 min. The anesthetic recovery time, from M0 to effortless bipedal position and adequate phalangeal flexion, was 99.3 ± 32.4 min. The sedation was assessed as intense, and the anesthetic recovery was rated excellent in 62.5% and good in 37.5% of the animals.(AU)

O presente estudo objetivou avaliar os efeitos do uso da cetamina S(+) 20 mg/kg associada à dexmedetomidina 25 µg/kg e butorfanol 0,4 mg/kg sobre os parâmetros fisiológicos, tempo e qualidade da recuperação anestésica de araracangas (Ara macao). Foram utilizados oito espécimes de Ara macao cativas da Fundação Zoobotânica de Marabá, Pará. A captura foi realizada com o uso de puçá e rede de contenção e em seguida as aves foram submetidas ao protocolo proposto. Foram avaliados: frequência cardíaca, frequência respiratória, saturação parcial da oxihemoglobina (SpO2), temperatura corporal e pressão arterial não-invasiva a partir de 5 minutos após a aplicação dos fármacos (M0) e a cada 10 minutos seguintes (M1, M2, M3, M4 e M5), totalizando 55 minutos de contemplação dos efeitos anestésicos. A glicemia foi avaliada aos 5 minutos da aplicação dos fármacos e repetida após 30 minutos. Também foi determinado o tempo de indução e de recuperação. Dentre os parâmetros avaliados, a frequência cardíaca e a temperatura demonstraram queda estatisticamente significativa ao longo do período anestésico, ambas com os menores valores registrados aos 55 minutos após a aplicação dos fármacos (M5). A frequência respiratória não apresentou diferença estatística e todos os animais se mantiveram estáveis e com a frequência próxima a média de 20±8mpm. A saturação da oxihemoblobina (SpO2) ao longo do período anestésico foi de 92±5%, não houve diferença estatisticamente relevante, as aves permaneceram sob ventilação espontânea e sem suplementação de oxigênio. As pressões arteriais sistólica, diastólica e média, mantiveram-se estáveis e não houve diferença estatística para nenhuma dessas medidas. A glicemia, mensurada em M0 e M3 demonstrou queda discreta, sem diferença significativa capaz de justificar um efeito adverso ou mesmo hipoglicemia. O tempo de indução, desde aplicação dos anestésicos até o decúbito, foi de 2,4±0,7 minutos. O tempo de recuperação, compreendido desde a aplicação dos fármacos (M0) até a constatação da posição bipedal sem esforço e adequada flexão das falanges, foi de 99,3±32,4 minutos. A qualidade de sedação foi considerada intensa e a recuperação anestésica foi classificada como ótima para 62,5% e boa para 37,5% dos animais.(AU)

Nouvelles thérapies dans la prise en charge du patient avec maladie rénale chronique souffrant de prurit : une revue de la littérature New therapies in the management of chronic kidney disease associated pruritus.

Chronic Kidney Disease associated Pruritus (CKD-aP) is a well-established and frequent complication observed in patient with CKD, especially in dialysis patients. However, the management of CKD-aP remains a challenge as the pathophysiology and research studies are too small. Finally, there are a few proposed treatment options with significant clinical benefits. This general review will summarize all the available treatments for the CKD-aP and will highlight the clinical efficacy and limits of the current drugs. Notably, we will focus on the implication of the opioid receptor in the pathophysiology of the CKD-aP and the recently Kappa opioid receptor agonist. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.

A retrospective analysis of pain changes and opioid use patterns temporally associated with a course of chiropractic care at a publicly funded inner-city facility.

Background: Non-pharmacologic treatment, including chiropractic care, is now recommended instead of opioid prescriptions as the initial management of chronic spine pain by clinical practice guidelines. Chiropractic care, commonly including spinal manipulation, has been temporally associated with reduced opioid prescription in veterans with spine pain. Purpose: To determine if chiropractic management including spinal manipulation was associated with decreased pain or opioid usage in financially disadvantaged individuals utilizing opioid medications and diagnosed with musculoskeletal conditions. Methods: A retrospective analysis of quality assurance data from a publicly funded healthcare facility was conducted. Measures included numeric pain scores of spine and extremity regions across three time points, opioid utilization, demographics, and care modalities. Results: Pain and opioid use significantly decreased concomitant with a course of chiropractic care. Conclusions: A publicly funded course of chiropractic care temporally coincided with statistically and clinically significant decreases in pain and opioid usage in a financially disadvantaged inner-city population.

Contexte: Conformément aux directives de pratique clinique, un traitement non pharmacologique, notamment des soins chiropratiques, à la place de prescriptions d'opioïdes est désormais recommandé dans le traitement initial de la douleur chronique à la colonne vertébrale. Les soins chiropratiques, qui comprennent habituellement la manipulation vertébrale, ont été liés de manière provisoire à une consommation réduite d'opioïdes sur ordonnance chez les vétérans souffrant de douleurs à la colonne vertébrale. Objectif: Déterminer si un traitement chiropratique, y compris la manipulation vertébrale, était lié à une diminution de la douleur ou de la consommation d'opioïdes chez les personnes défavorisées sur le plan financier utilisant des médicaments à base d'opioïdes et souffrant de problèmes musculosquelettiques. Méthodologie: Une analyse rétrospective des données sur l'assurance de la qualité provenant d'un établissement de soins de santé financé par l'État a été menée. Les mesures portaient sur des résultats numériques de la douleur à la colonne vertébrale et des extrémités des membres à trois moments différents, la consommation d'opioïdes, des données démographiques et les modes de soins. Résultats: La douleur et la consommation d'opioïdes ont sensiblement diminué dans le cadre de soins chiropratiques. Conclusions: Une diminution importante de la douleur et de la consommation d'opioïdes observée de façon statistique et clinique a coïncidé de manière provisoire avec des soins chiropratiques financés par l'État dans un groupe de personnes défavorisées sur le plan financier vivant au centre-ville.

[Noninvasive Treatments for Acute and Chronic Back Pain]. / Nicht-invasive Therapieansätze bei akuten und chronischen Rückenschmerzen.

Noninvasive Treatments for Acute and Chronic Back Pain Abstract. The therapy of back pain - especially the medication with opioids - can be challenging for the treating physician. Specific back pain can often be diagnosed by imaging and successfully treated by surgery or medication. In contrast, nonspecific back pain can be worsened by inappropriate imaging, questionable surgical indications and uncontrolled drug use. For the therapy of nonspecific back pain, maintaining daily activity and exercise therapy is central. Opioids are effective drugs for short-term use. However, long-term use often leads to opioid-induced hyperalgesia and hormonal dysfunction with decreased quality of life and libido. Furthermore, opioids can lead to abuse and addiction. After an ineffective treatment with non-opioids, opioids may be given for a limited time period (if possible shorter than four weeks) according to international guidelines.

Opioid receptor µ, not δ and κ, modulate food intake induced by ghrelin in laying chickens.

Evidence from animal studies suggests that the opioidergic system and ghrelin have a regulatory role in food intake, but their interaction(s) have not been studied in laying chickens. So in this study, four experiments (each included four groups) were designed. The first experiment was performed to evaluate the effect of ghrelin on the cumulative food intake. Experiments 2-4 were designed to investigate the possibility of µ, δ, or κ opioid receptors mediating ghrelin-induced hypophagia. All drugs were injected intracerebroventricularly (ICV) at 5 days of age. The results of this study showed that the ICV injection of 1.5 nmol ghrelin did not affect cumulative food intake. However, ICV injection of ghrelin with doses of 3 and 6 nmol significantly reduced the cumulative food intake (p < 0.05). However, co-injection of ghrelin with naltrindole and norbinaltorphimine did not show a significant change in decreased food intake compared with ghrelin. Also, opioid µ receptor gene expression significantly increased (p < 0.05), but δ and κ opioid receptors' gene expression did not significantly change. These results indicated that the opioidergic system is involved in developing ghrelin-induced hypophagic effects in laying chickens. Accordingly, this effect of ghrelin to modify the nutritional behavior is possibly mediated by opioid µ receptor.

Administración prolongada de morfina intratecal por bomba de infusión implantada, en un caso de dolor crónico no oncológico / Prolonged administration of intratecal morphine by infusion pump implanted in a case of non-oncological chronic pain / Administração prolongada de morfina intratecal por bomba de infusão implantada, em caso de dor crônica não oncológica

Introducción: Se describe la evolución de un paciente que recibe morfina intratecal mediante una bomba de infusión, que le fuera implantada hace 14 años para tratamiento de su dolor lumbar crónico post-laminectomía. Material y método: Requería la administración de 60 mg/día de morfina subcutánea que le provocaban efectos secundarios que no toleraba, y múltiples internaciones para control del dolor. Se le implantó una bomba de infusión continua (Isomed) conectada a un catéter subaracnoideo, que libera 1 ml/día, y requiere ser llenada cada 60 días. Resultados: Se observó una disminución del dolor promedio de 50% al año, y de 75% a los 6 y 14 años. Requirió un aumento progresivo de las dosis de llenado, que pasaron de 30 mg de morfina (0.5 mg/día) al inicio, a 40 mg de morfina (0.66 mg /día) al año, a 70 mg de morfina (1.16 mg/día) a los 6 años, a 140 mg (2.33 mg/día) a los 14 años. No se registraron complicaciones médicas graves. Mantuvo constipación y sudoración durante todo el período, e instaló un hipogonadismo secundario con trastornos de la libido y de la erección que fueron corregidos con la administración de testosterona. No requirió más internaciones por dolor. No se observaron complicaciones relacionadas con el funcionamiento o llenado de la bomba, ni vinculadas al catéter. El paciente manifestó estar satisfecho con el implante. Discusión: A pesar del aumento de las dosis de llenado, expresión del desarrollo de tolerancia, las dosis de morfina/día requeridas son francamente inferiores al límite recomendado. Conclusiones: El balance del riesgo-beneficio del implante resultó positivo, considerando el mejor control del dolor logrado, las menores dosis de morfina utilizadas, así como la ausencia de complicaciones graves y de internaciones para control del dolor.

Introduction: The evolution of a patient receiving intrathecal morphine through an infusion pump that was implanted 14 years ago for the treatment of chronic post-laminectomy low back pain is described. Material and method: It required the administration of 60 mg / day of subcutaneous morphine that caused side effects that did not tolerate, and multiple hospitalizations for pain control. He was implanted with a continuous infusion pump (Isomed) connected to a subarachnoid catheter, which releases 1 ml / day, and needs to be filled every 60 days. Results: An average pain decrease of 50% per year, and 75% at 6 and 12 years was observed. It required a progressive increase in filling doses, which went from 30 mg of morphine (0.5 mg / day) at the beginning, to 40 mg of morphine (0.66 mg / day at the first year, to 70 mg of morphine (1.16 mg / day) at the sixth year, at 140 mg (2.33 mg / day) at the fourteen year. No serious medical complications were recorded, he maintained constipation and sweating throughout the period, and installed secondary hypogonadism with libido and erection disorders, that were corrected with the administration of testosterone. No further hospitalizations were required due to pain. No complications were observed related to the operation or filling of the pump or linked to the catheter. The patient stated that he was satisfied with the implant. Discussion: Despite the increase in filling doses, expression of tolerance development, the required morphine / day doses are frankly below the recommended limit. Conclusions: The risk-benefit balance of the implant was positive, considering the best pain control, the lowest doses used, the absence of serious complications, and the lack of hospitalizations for pain control.

Introdução: Descreve-se a evolução de um paciente que recebeu morfina intratecal através de uma bomba de infusão, implantada há 14 anos para o tratamento de lombalgia crônica pós-laminectomia. Material e método: Necessitou de administração de 60 mg/dia de morfina por via subcutânea, que provocou efeitos colaterais intolerantes, e múltiplas internações para controle da dor. Foi implantada uma bomba de infusão contínua (Isomed) conectada a um cateter subaracnóideo, que libera 1 ml/dia, necessitando de reenchimento a cada 60 dias. Resultados: Observou-se redução média da dor de 50% em um ano e 75% em 6 e 14 anos. Foi necessário um aumento progressivo das doses de enchimento, que passaram de 30 mg de morfina (0,5 mg/dia) no início, para 40 mg de morfina (0,66 mg/dia) por ano, para 70 mg de morfina (1,16 mg/dia) dia) aos 6 anos, para 140 mg (2,33 mg/dia) aos 14 anos. Não foram registradas complicações médicas graves. Manteve constipação e sudorese durante todo o período e desenvolveu hipogonadismo secundário com distúrbios de libido e ereção que foram corrigidos com administração de testosterona. Ele não necessitou de mais hospitalizações por dor. Não foram observadas complicações relacionadas à operação ou enchimento da bomba, ou relacionadas ao cateter. O paciente afirmou estar satisfeito com o implante. Discussão: Apesar do aumento das doses de enchimento, expressão do desenvolvimento da tolerância, as doses necessárias de morfina/dia são francamente inferiores ao limite recomendado. Conclusões: A relação risco-benefício do implante foi positiva, considerando o melhor controle da dor alcançado, as menores doses de morfina utilizadas, bem como a ausência de complicações graves e internações para controle da dor.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

Bone pain management with opioid medication in a patient with Camurati-Engelmann disease: a case report / Manejo del dolor óseo con medicación opioide en una paciente con enfermedad de Camurati-Engelmann: reporte de un caso

Introduction: Camurati-Engelman Disease is a rare genetic sclerosing bone dysplasia with periosteal and endosteal thickening of the cortical of the long bones. It generates pain secondary to the reduction of the medullary canal that is usually controlled with corticosteroids and, in severe cases, with surgical decompression. Case history: We present the case of a woman with a genetic diagnosis of Camurati-Engelman Disease with poor pain control with corticosteroid management and surgical procedures throughout her childhood and early adulthood. In whom optimal pain control was achieved with pain regimen with hydrocodone analgesic management. This is the first case described in the literature for adequate pain control using an opioid drug. Discussion: CE disease is an extremely rare genetic entity with little more than 300 cases reported in the world. It is generated by an alteration in the gene for growth factor-beta 1 (TGF-B1); it has a varied clinical presentation that can begin with bone alterations accompanied by muscle weakness, joint angular alterations, headache, and nerve compressions. It has a differential diagnosis with some genetic entities that may present clinical similarity, but its morphological and radiological characteristics are distinctive. The usual management of bone pain generated by this entity is based on corticosteroids, in addition to losartan or surgical intervention aimed at reducing cortical changes. The intervention with opioid analgesics accompanied by a rehabilitation plan is not a frequent report, this being a case of success due to the refractoriness of the symptoms in a patient with chronic pain, with a positive impact on her functionality and quality of life. Conclusion: It is considered that analgesic management with opioids may be a treatment option in patients with Camurati-Engelman disease refractory to corticosteroid management and surgical interventions.(AU)

Introducción: La enfermedad de Camurati-Engelman (CE) es una displasia ósea esclerosante rara, de causa genética. Se presenta con engrosamiento perióstico y endóstico de la cortical de los huesos largos. Genera dolor secundario a la reducción del canal medular, que habitualmente se controla con corticoides y en casos severos, con descompresión quirúrgica. Historia del caso: Presentamos el caso de una mujer con diagnóstico genético de enfermedad de Camurati-Engelman, con mal control del dolor, con manejo de corticosteroides y procedimientos quirúrgicos a lo largo de su niñez y adultez temprana. Se logró un control óptimo del dolor con un régimen con manejo analgésico con hidrocodona. Este es el primer caso descrito en la literatura de un adecuado control del dolor con un medicamento opioide. Discusión: La enfermedad de CE es una entidad genética extremadamente rara, con poco más de 300 casos reportados en el mundo. Se genera por una alteración en el gen del factor de crecimiento beta 1 (TGF-B1). Tiene una presentación clínica variada que puede iniciar con las alteraciones óseas acompañado de debilidad muscular, alteraciones angulares articulares, cefalea y compresiones nerviosas. Tiene diagnóstico diferencial con algunas entidades genéticas que pueden presentar similitud clínica, pero su característica morfológica y radiológica es distintiva. El manejo usual del dolor óseo generado por esta entidad se basa en corticoesteroides, además de losartán o intervenciones quirúrgicas orientadas a disminuir los cambios corticales. La intervención con analgésicos opioides, acompañada de un plan de rehabilitación, no es un reporte frecuente, siendo este un caso de éxito ante la refractariedad de los síntomas en una paciente con dolor crónico, impactando de manera positiva en su funcionalidad y calidad de vida.(AU)

Efficacy of Transversus Abdominis Plane Block in the Reduction of Pain and Opioid Requirement in Laparoscopic and Robot-assisted Hysterectomy: A Systematic Review and Meta-analysis / Eficácia do bloqueio transverso do plano abdominal na redução da dor e da necessidade de opioides em histerectomia laparoscópica e assistida por robô: Uma revisão sistemática e metanálise

Abstract Objective To summarize the available evidence of TAP Block in efficacy in laparoscopic or robotic hysterectomy. Data Sources We searched databases and gray literature for randomized controlled trials in which transversus abdominis plane (TAP) block was compared with placebo or with no treatment in patients who underwent laparoscopic or robot-assisted hysterectomy. Method of Study Selection Two researchers independently evaluated the eligibility of the selected articles. Tabulation, Integration, and Results Seven studies were selected, involving 518 patients. Early postoperative pain showed a difference in the mean mean difference (MD): - 1.17 (95% confidence interval [CI]: - 1.87-0.46) in pain scale scores (I2=68%), which was statistically significant in favor of using TAP block, but without clinical relevance; late postoperative pain: DM 0.001 (95%CI: - 0.43-0.44; I2=69%); opioid requirement: DM 0.36 (95%CI: - 0.94-1.68; I2=80%); and incidence of nausea and vomiting with a difference of 95%CI=- 0.11 (- 0.215-0.006) in favor of TAP. Conclusion With moderate strength of evidence, due to the high heterogeneity and imbalance in baseline characteristics among studies, the results indicate that TAP block should not be considered as a clinically relevant analgesic technique to improve postoperative pain in laparoscopic or robotic hysterectomy, despite statistical significance in early postoperative pain scale scores. Clinical Trial Number and Registry: PROSPERO ID - CRD42018103573.

Resumo Objetivo Resumir as evidências disponíveis sobre a eficácia do bloqueio TAP em histerectomia laparoscópica ou robótica. Fontes de Dados Pesquisamos bancos de dados e literatura cinza por ensaios clínicos randomizados nos quais o bloqueio do plano transverso do abdome (TAP na sigla em inglês) foi comparado com placebo ou com nenhum tratamento em pacientes que foram submetidos a histerectomia laparoscópica ou assistida por robô. Métodos de Seleção de Estudos Dois pesquisadores avaliaram independentemente a elegibilidade dos artigos selecionados. Tabulação, Integração e Resultados Sete estudos foram selecionados envolvendo 518 pacientes. A dor pós-operatória precoce apresentou diferença nasmédias (DM) de: -1 17 (intervalo de confiança [IC] de 95%: - 1 87-0 46) nos escores da escala de dor (I2=68%) o que foi estatisticamente significativo a favor do uso do bloqueio TAP mas sem relevância clínica; dor pós-operatória tardia: DM 0001 (IC95%: - 043-044; I2=69%); necessidade de opioides: DM0 36 (95%CI: - 0 94-168; I2=80%); e incidência de náuseas e vômitos com diferença de 95% CI=- 011 (- 0215-0006) a favor do TAP. Conclusão Com moderada força de evidência devido à alta heterogeneidade e ao desequilíbrio nas características basais entre os estudos os resultados indicam que o bloqueio do TAP não deve ser considerado como uma técnica analgésica clinicamente relevante para melhorar a dor pós-operatória em histerectomia laparoscópica ou robótica apesar da significância estatística nas pontuações da escala de dor pósoperatória inicial. Número e Registro do Ensaio Clínico: PROSPERO ID - CRD42018103573.

[Early maladaptive schemes and relapse during methadone maintenance treatment among drug addicts (a cognitive approach)]. / Les schémas précoces inadaptés et la rechute au cours de traitement de maintien par la méthadone chez les toxicomanes (une approche cognitive).

INTRODUCTION/OBJECTIVE: Dysfunction of cognitive schemas and addictive behaviors are often coexisting which can cause relapse during drug treatment. The objective of this study is to assess early maladaptive schemas (EMS) among heroin users and their relationship with relapse during methadone maintenance treatment. SUBJECT AND METHODS: This is a cross-sectional study carried out on 166 heroin users treated with methadone at the medico-psychological center in northern Morocco during 2017. The subjects completed both the Young short version schema questionnaire (YQS) and the ASI questionnaire (Addiction Severity Index) to measure the severity of drug addiction. RESULTS: The results showed that the most activated schemas in the totality of the subjects were fear of losing control, Emotional deficiency and failure. They were also significantly more activated in women than in men for five schemas indicating rejection and separation, and a lack of autonomy. Regarding the relapse during treatment consumption there was a positive and significant correlation with ten out of thirteen SPI, which means the more the intensity of SPI decrease the greater the tendency to relapse (r=0.509, P<0.0001). However, there was also a weak correlation between the consumption of other drugs and SPI. CONCLUSION: The cognitive approach has highlighted the essential role of cognitive disorders in addictive behaviors that EMS may be predictors of relapse during substitution treatment, and that a concurrent therapy of schema may reduce the likelihood of relapse.