Influence du sommeil sur l'analgésie placebo

La douleur est une expérience subjective multidimensionnelle pouvant être modulée par plusieurs facteurs cognitifs. L’impact des attentes liées à une expérience douloureuse imminente a été largement étudié dans un contexte d’analgésie placebo et il a été suggéré que la présence d’attentes conscientes de soulagement est nécessaire à la production d’une réduction de douleur. Par ailleurs, certaines études cliniques ont observé une amélioration thérapeutique après l’administration d’un placebo, même lors du sommeil, ce qui suggère qu’un effet placebo peut être rencontré même en absence d’attentes explicites de soulagement. La première étude de cette thèse vise donc à examiner si une réduction de douleur, ainsi qu’une diminution des perturbations du sommeil associées à des stimulations nociceptives expérimentales, peuvent être rencontrées suite à l’induction d’attentes de soulagement nocturne. Les résultats démontrent qu’une réduction de douleur et des perturbations du sommeil a effectivement été rapportée rétrospectivement suite à l’application d’un placebo, De plus, le traitement placebo semble moduler la réactivité à la douleur expérimentale durant le sommeil, en fonction des stades de sommeil dans lesquelles les stimulations sont présentées. Bien que le développement d’une analgésie placebo repose sur la génération d’attentes de soulagement, il semble que l’exposition préalable à un traitement efficace augmente l’ampleur de l’effet, ce qui suggère que des phénomènes d’apprentissage associatif puissent également être impliqués dans la genèse de ces effets. Comme un rôle du sommeil à été montré dans l’apprentissage et la mémorisation de plusieurs aptitudes, l’objectif de la seconde étude était d’examiner la possibilité que la présence d’un épisode de sommeil entre l’induction et l’évaluation d’un effet placebo puisse renforcer l’intégration des attentes et par conséquent, favoriser la production d’effets dépendants des attentes. Les résultats ont effectivement montré que le sommeil augmente l’association entre les attentes et le soulagement, et que celles-ci semblent liées à la durée relative de sommeil REM mesurée suite à l’induction. Dans l’ensemble cette thèse démontre que le sommeil peut influencer la production d’une analgésie placebo, et ce, à plusieurs niveaux.

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Perineal Analgesia With an Ice Pack After Spontaneous Vaginal Birth: A Randomized Controlled Trial

Methods: We conducted a randomized controlled trial at the Amparo Maternal Birth Center in Sao Paulo, Brazil. Study participants included 114 nulliparous women divided into 3 groups (n = 38 per group): experimental (ice packs on the perineum), placebo (water packs at set temperature), and control (no treatment). Results: A numerical scale (0 to 10) was used for pain assessment. A comparison of the average pain at the beginning and after 20 minutes showed a significant reduction of pain (P < .001) in the 3 groups, and the experimental group had a lower average score for pain compared with the control group (1.6 versus 3.3, P = .032). Discussion: The use of ice packs for 20 minutes was effective for perineal pain relief after vaginal birth.

Neuropharmacological basis of rTMS-induced analgesia: The role of endogenous opioids

We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10 Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15 degrees C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1 mg/kg followed by a continuous infusion of 0.1 mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. (C) 2010 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.

The use of different doses of metamizol for post-operative analgesia in dogs

Objective To evaluate the post-operative analgesic effect of metamizol (dipyrone) administered intravenously at three different doses (15 mg kg(-1), 25 mg kg(-1) and 35 mg kg(-1)) compared to placebo in dogs undergoing ovariohysterectomy. Study design Prospective, comparative, randomized. blinded trial. Animals Forty healthy bitches, aged 1-6 years, weighing 10-35 kg Methods The animals were randomly divided into four groups and received their respective treatments immediately after surgery: placebo group (0.9% saline solution), D15 group (metamizol 15 mg kg(-1) IV), D25 group (metamizol 25 mg kg(-1) IV), D35 group (metamizol 35 mg kg(-1) IV). The following variables were measured: sedation, pulse rate (PR). respiratory rate (f(R)). arterial blood pressure (ABP), plasma catecholamines. serum cortisol, blood urea nitrogen (BUN) and creatinine metabolites. albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP). hemogram. platelet counts and level of analgesia which was assessed by visual analog (VAS). descriptive and behavioral scales. Patients were monitored for 48 hours after the administration of the analgesic agent. Rescue analgesia (tramadol, 2 mg kg(-1), intramuscularly) was provided for animals with pain scores >= 4, as determined by the VAS or descriptive scale. Results The D25 and D35 groups showed equivalent post-operative analgesia, as shown by decreased pain scores, according to the three different pain scales, and fewer animals that required rescue analgesia. Significantly lower serum cortisol concentrations were observed in the D25 and D35 groups when compared to the placebo and D15 groups. No hematologic, renal, hepatic or clinical adverse effects were observed during the treatment. Conclusions and clinical relevance Metamizol administered intravenously at 25 or 35 mg kg(-1) can provide adequate post-operative analgesia in bitches undergoing ovariohysterectomy.

Modification of induced ischaemic pain by placebo electrotherapy

Quantifying the analgesic effect of placebo electrotherapy is an important part of understanding the placebo response in physiotherapy. This repeated measures study of induced ischaemic pain compared reports of pain threshold, pain tolerance, and pain endurance under three conditions: control, placebo interferential, and placebo TENS. Both of the placebo conditions significantly delayed the report of pain threshold. Placebo interferential also delayed pain tolerance. Each placebo condition reduced pain intensity in the 6th minute. Only placebo TENS reduced pain at the 9th minute of ischaemic pain. The nature of pain reduction in the placebo conditions suggests that analgesia was due to learned expectancies and endogenous opioid release. Further research into the impact of positive expectancies of pain relief in our patients could clarify the efficacy of physiotherapy outcomes for pain.

Analgesic efficacy of intravenous perfusion of lidocaine, ketamine or a combination after laparotomy in a placebo-controlled, randomized, double-blind prospective study

In acute postoperative pain management intravenous lidocaine and/or ketamine have been advocated because of their morphine-sparing effect. The goal of this prospective, randomised, double-blind study was to assess morphine consumption with different regimens of intravenous infusion of lidocaine, ketamine or both during 48 hours following laparotomy. Patients were randomised into four groups. Group L, K, and KL received intravenous lidocaine, ketamine or a combination, respectively, before incision and during 48 hours postoperatively. The control group (C) received a similar volume of saline bolus and infusion. Postoperative analgesia included morphine delivered by a patient-controlled analgesia device. Primary outcome was the cumulative morphine consumption and pain, sedation scores, pressure algometry and side effects were our secondary outcomes. Cognition and psychomotor performance were also tested. Out of 57 eligible patients, 44 completed the study. Lidocaine reduced the cumulative morphine consumption compared with the control group (mean 0.456 mg.kg-1 +/- 0.244 (SD) versus 0.705 +/- 0.442, respectively, Ρ < 0.001). Pain scores during movement were statistically lower in all three treatment groups. Psychometric tests showed that the lidocaine group expressed more depressed feelings and sadness compared to the control group. Lidocaine administration had a morphine-sparing effect with a 36% reduction of morphine consumption while ketamine alone or combined with lidocaine did not. As a whole, our results suggest that intravenous lidocaine may offer advantages for postoperative analgesia. We propose lidocaine as a new alternative for pain control that needs to be studied further in future multicentric studies.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Avaliação do efeito analgésico preemptivo do lumiracoxibe comparado com placebo nas primeiras 24 horas de pós-operatório

OBJETIVO: Testar o lumiracoxibe, utilizado preemptivamente contra um placebo, e analisar o consumo de analgésicos (dipirona e tramadol) nas primeiras 24h do pós-operatório. MÉTODOS: Sessenta pacientes submetidas à mamoplastia de aumento, sob anestesia peridural, foram selecionadas e divididas de forma randomizada em dois grupos - GI e GII. Sessenta minutos antes da operação, por via oral, as 30 pacientes do GI receberam um comprimido de lumiracoxibe 400mg, e as 30 do GII um comprimido de placebo. A dor pós-operatória foi avaliada através da escala analógica visual, graduada de 0 (sem dor) a 10 (dor de maior intensidade), sendo aplicada sempre que houvesse referência de dor. Para escores obtidos iguais ou menores que 4, a paciente recebia 15mg/kg de dipirona, até máximo de um grama, via venosa. Para escores de 5, 6 ou 7, recebia 50mg de tramadol por via venosa. Escores de 8 ou mais eram tratados com 0,5mg/kg de meperidina endovenosa. RESULTADOS: Os escores obtidos no GI foram significativamente menores que os do GII dentro das primeiras 24 horas, resultando em consumo 20% menor de dipirona e 56% menor de tramadol. Da mesma forma, observou-se que o tempo para solicitação de analgésicos pela primeira vez no pós-operatório foi de 191 minutos maior no GI. CONCLUSÃO: O emprego do lumiracoxibe preemptivamente mostrou-se efetivo no combate à dor pós-operatória, reduzindo consideravelmente o consumo global de analgésicos nesse período e aumentando o tempo de solicitação de analgésico pela primeira vez.

Postoperative topical analgesia of hemorrhoidectomy with policresulen and cinchocaine: a prospective and controlled study

OBJECTIVE: To evaluate the effects of topical policresulen and cinchocaine in the postoperative pain behavior of open hemorrhoidectomy.METHODS: We conducted a prospective, double-blinded, controlled study. The control group received the usual guidelines with oral medications. The topical treatment group received, in addition, the application of the ointment and was comprised of two subgroups (policresulen + cinchocaine, and placebo). Pain intensity was recorded with the visual analogue scale.RESULTS: 43 patients were operated on: control group - n = 13, one excluded; placebo - n = 15; and policresulen + cinchocaine - n = 15. The mean age was 45.98 years and 37.2% were men. The average pain intensity was 4.09 (immediate postoperative), 3.22 (hospital discharge), 5.73 (day 1) , 5.77 (day 2), 5.74 (day 3), 5.65 (day 7), 5.11 (day 10), 2.75 (day 15) and 7.70 (first bowel movement), with no difference between groups in all periods.CONCLUSION: This study showed no reduction in pain after hemorrhoidectomy with the use of topical policresulen and cinchocaine.

Analgesia peridural para o trabalho de parto e para o parto: efeitos da adição de um opióide

O objetivo deste estudo foi avaliar a eficácia e segurança da associação bupivacaína com sufentanil para a analgesia no trabalho de parto e do parto por meio de um bloqueio peridural contínuo. Realizou-se um ensaio clínico duplo-cego, prospectivo e aleatório, incluindo sessenta mulheres nulíparas da Maternidade do CAISM/UNICAMP. No momento da analgesia, as mulheres foram aleatoriamente alocadas em dois grupos: BS, recebendo 12,5 mg de bupivacaína com adrenalina mais 30 µg de sufentanil e BP, recebendo 12,5 mg de bupivacaína com adrenalina mais placebo. Foram avaliados os parâmetros relativos à qualidade e duração da analgesia, duração do trabalho de parto e também possíveis efeitos sobre o recém-nascido. Os resultados mostraram a superioridade da adição do sufentanil sobre o grau de analgesia durante o tempo de ação da primeira dose de anestésico local. Não houve aumento na duração do trabalho de parto depois do início da analgesia quando se compararam ambos os grupos, nem qualquer diferença quanto à via de parto. Não houve também diferenças entre os grupos com relação à avaliação dos recém-nascidos. Conclui-se que a associação de 30 µg de sufentanil à primeira dose de bupivacaína é segura e eficaz, melhorando a qualidade da analgesia, sua duração e não afetando a progressão do trabalho de parto e o resultado neonatal.

Única dosis de gabapentin preoperatorio para analgesia postoperatoria: revisión de literatura

Introducción: el dolor postoperatorio supone un reto para todo anestesiólogo, en los últimos años se ha propuesto el Gabapentin preoperatorio como una buena opción paraanalgesia postoperatoria sin efectos secundarios. Metodología: se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. Resultados: se encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, Discusión: los resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cuál es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.Metodología Se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. ResultadosSe encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, DiscusiónLos resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cual es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.

Comparación entre analgesia epidural continua vs bloqueo nervio periférico en niños llevados a cirugía múltiple de miembros inferiores

Las cirugías reconstructivas múltiples de miembros inferiores son intervenciones quirúrgicas que implican un difícil manejo analgésico en el postoperatorio, actualmente la técnica analgésica usada es la analgesia peridural; sin embargo los efectos adversos asociados a esta no la hacen una técnica ideal para manejo de dolor. Los bloqueos de nervio periférico han aparecido como una alternativa para el manejo del dolor; pero no se ha difundido ampliamente su uso. Se pretende evaluar la disminución de efectos adversos con el uso de bloqueos de nervio periférico sobre la analgesia epidural. Este estudio piloto inicial se realizo para verificar efectividad técnicas a usar y problemas que se pudieran presentar. Se aplico el protocolo en 23 pacientes que fueron llevados a cirugía de miembros inferiores, se dividieron en 2 grupos 11 recibieron bloqueos de nervio periférico y 12 analgesia epidural. Se les realizo seguimiento por 48 horas y se evaluó el control del dolor, consumo de opioides y efectos adversos. El tiempo de colocación del bloqueo fue similar en ambos grupos, el grupo de bloqueos presento menos episodios de dolor y menos episodios de dolor severo. No se presento retención urinaria en ningún paciente pero en el grupo de epidural se presento mayor incidencia de nausea y vomito (60% vs 45%). Se encontró que los bloqueos de nervio periférico son una adecuada opción para el manejo del dolor en este tipo de cirugías; y al parecer disminuye la incidencia de eventos adversos asociados a la analgesia epidural.