Angela Maria Sousa

Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

Efeito analgésico local do tramadol em modelo de dor provocada por formalina em ratos

BACKGROUND AND OBJECTIVES Tramadol hydrochloride is known as a centrally acting analgesic drug, used for the treatment of moderate to severe pain. A local analgesic effect has been demonstrated, but its mechanism of action remains unclear. METHODS In this study, we examined the effect of local, systemic and nerve block tramadol on the nociceptive flinching behavior elicited by injection of 50 microL of 1% formalin into the dorsal region of hind paw of rats. Nociceptive flinching behavior was observed for 60 minutes. RESULTS Local tramadol in higher concentrations (2.5 and 5 mg) almost eliminated flinching behavior during the entire test. Systemic and neural block tramadol did not affect flinching behavior in phase I and partially decreased it in phase II. CONCLUSIONS Tramadol presented a local analgesic effect in formalin nociceptive flinching behavior that is different from its central analgesic effect. This analgesic effect, in this model, seems not to be linked to a local anesthetic like effect.

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats

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

Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: a double-blind randomized controlled trial

STUDY OBJECTIVE The aim of this study is to compare the analgesic effect of intravenous infusion of magnesium sulfate to ketorolac during laparoscopic surgeries. DESIGN Double-blind randomized controlled trial. SETTING University-affiliated teaching hospital. PATIENTS Sixty women submitted to laparoscopic gynecologic oncology surgeries. INTERVENTIONS Intravenous ketorolac 30 mg in bolus followed by saline infusion (group K), intravenous magnesium sulfate 20 mg/kg in bolus followed by magnesium 2 mg kg(-1) h(-1) (group M) or intravenous saline solution 20 mL in bolus followed by saline infusion during the entire procedure (group S). MEASUREMENTS Postoperative pain, nausea, vomiting, sedation, opioid consumption, time to first dose of analgesic. MAIN RESULTS Magnesium sulfate reduced opioid consumption compared with placebo in the postoperative, but not in the intraoperative, period. Nausea, not vomiting, was reduced in ketorolac but not in the magnesium group. Pain intensity was higher in placebo than in the other 2 groups during all periods of observation. In the first 60 minutes, pain intensity was lower in the magnesium than in the ketorolac or the placebo group. CONCLUSION Intraoperative magnesium sulfate improves postoperative pain control, acting as an opioid-sparing adjuvant, and is similar to ketorolac 30 mg administered in the beginning of surgery.

Analgesic effects of H1 receptor antagonists in the rat model of formalin-induced pain

BACKGROUND AND OBJECTIVES Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS To answer this question, we used three different H1 receptor antagonists (pyrilamine, promethazine, and cetirizine) administered directly in the paw of the rat, intraperitoneally, or in peripheral nerve blockade in the formalin-induced pain model. The effects of the drugs on the number of paw elevations were observed. RESULTS In phase I, the local administration of pyrilamine caused a dose-dependent reduction on the number of paw elevations; in the highest dose, the number of paw elevations was reduced by 97.8%. Promethazine decreased it by 92%, while cetirizine decreased by 23.9%. In phase II, pyrilamine decreased the number of paw elevations by 93.5%, promethazine by 78.2%, and cetirizine by 80.1%. Intraperitoneal administration of drugs did not change painful behavior. When used in peripheral nerve block, in phase I pyrilamine reduced the number of paw elevations by 96.7%, promethazine by 73.3%, and cetirizine by 23.9%. In phase II, pyrilamine reduced the number of paw elevations by 86.6%, promethazine by 64.4%, and cetirizine by 19.9%. CONCLUSIONS The results demonstrate that H1 receptor antagonists have local analgesic effects, different from the systemic effects, one of them an anti-inflammatory and class-specific effect and the other similarly to the local anesthetic effect, specific for promethazine and pyrilamine.JUSTIFICATIVA Y OBJETIVOS: Los receptores de histamina intermedian las vias nociceptivas, principalmente en el sistema nervioso central. Algunos estudios arrojaron un efecto analgesico de antagonistas de receptor de histamina en el sistema nervioso periferico. No queda claro si el efecto analgesico local es de clase especifico o un farmaco especifico. METODO: Para responder a esa pregunta, utilizamos tres diferentes antagonistas del receptor H1 (pirilamina, prometazina y cetirizina), administrados directamente en la pata del raton, por via intraperitoneal o por bloqueo de nervio periferico en modelo de dolor inducido por formalina. Observamos el efecto de los farmacos en el comportamiento del numero de elevaciones de la pata. RESULTADOS: En la fase I, la pirilamina local redujo el numero de elevaciones de la pata de forma dosis dependiente. En la dosis mas alta, la reduccion fue de un 97,8%. Para la prometazina, la disminucion fue de un 92% y para la cetizirina de 23.9%. En la fase II, la pirilamina redujo el numero de elevaciones de la pata en un 93,5%, la prometazina, un 78,2% y la cetirizina un 80,1%. La administracion de los farmacos por via intraperitoneal no altero el comportamiento doloroso. Cuando se usaron para bloqueo del nervio periferico en la fase I, la pirilamina redujo el numero de elevaciones de la pata en un 96,7%, la prometazina en un 73,3% y la cetirizina en un 23,9%. En la fase II, la pirilamina redujo un 86,6%, la prometazina un 64,4% y la cetirizina un 19,9%. CONCLUSIONES: Los resultados mostraron que los antagonistas del receptor de la histamina H1 presentaron efectos analgesicos locales, diferentes del efecto sistemico, siendo uno de ellos antiinflamatorio y clase especifico, y el otro especifico para la prometazina y la pirilamina, parecido con el efecto clinico anestesico local.

Efeito analgésico de antagonistas do receptor da histamina H1 em modelo de dor provocada por formalina em ratos

BACKGROUND AND OBJECTIVES Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS To answer this question, we used three different H1 receptor antagonists (pyrilamine, promethazine, and cetirizine) administered directly in the paw of the rat, intraperitoneally, or in peripheral nerve blockade in the formalin-induced pain model. The effects of the drugs on the number of paw elevations were observed. RESULTS In phase I, the local administration of pyrilamine caused a dose-dependent reduction on the number of paw elevations; in the highest dose, the number of paw elevations was reduced by 97.8%. Promethazine decreased it by 92%, while cetirizine decreased by 23.9%. In phase II, pyrilamine decreased the number of paw elevations by 93.5%, promethazine by 78.2%, and cetirizine by 80.1%. Intraperitoneal administration of drugs did not change painful behavior. When used in peripheral nerve block, in phase I pyrilamine reduced the number of paw elevations by 96.7%, promethazine by 73.3%, and cetirizine by 23.9%. In phase II, pyrilamine reduced the number of paw elevations by 86.6%, promethazine by 64.4%, and cetirizine by 19.9%. CONCLUSIONS The results demonstrate that H1 receptor antagonists have local analgesic effects, different from the systemic effects, one of them an anti-inflammatory and class-specific effect and the other similarly to the local anesthetic effect, specific for promethazine and pyrilamine.JUSTIFICATIVA Y OBJETIVOS: Los receptores de histamina intermedian las vias nociceptivas, principalmente en el sistema nervioso central. Algunos estudios arrojaron un efecto analgesico de antagonistas de receptor de histamina en el sistema nervioso periferico. No queda claro si el efecto analgesico local es de clase especifico o un farmaco especifico. METODO: Para responder a esa pregunta, utilizamos tres diferentes antagonistas del receptor H1 (pirilamina, prometazina y cetirizina), administrados directamente en la pata del raton, por via intraperitoneal o por bloqueo de nervio periferico en modelo de dolor inducido por formalina. Observamos el efecto de los farmacos en el comportamiento del numero de elevaciones de la pata. RESULTADOS: En la fase I, la pirilamina local redujo el numero de elevaciones de la pata de forma dosis dependiente. En la dosis mas alta, la reduccion fue de un 97,8%. Para la prometazina, la disminucion fue de un 92% y para la cetizirina de 23.9%. En la fase II, la pirilamina redujo el numero de elevaciones de la pata en un 93,5%, la prometazina, un 78,2% y la cetirizina un 80,1%. La administracion de los farmacos por via intraperitoneal no altero el comportamiento doloroso. Cuando se usaron para bloqueo del nervio periferico en la fase I, la pirilamina redujo el numero de elevaciones de la pata en un 96,7%, la prometazina en un 73,3% y la cetirizina en un 23,9%. En la fase II, la pirilamina redujo un 86,6%, la prometazina un 64,4% y la cetirizina un 19,9%. CONCLUSIONES: Los resultados mostraron que los antagonistas del receptor de la histamina H1 presentaron efectos analgesicos locales, diferentes del efecto sistemico, siendo uno de ellos antiinflamatorio y clase especifico, y el otro especifico para la prometazina y la pirilamina, parecido con el efecto clinico anestesico local.

Local effect of tramadol on formalin evoked flinching behavior in rats

BACKGROUND AND OBJECTIVES Tramadol hydrochloride is known as a centrally acting analgesic drug, used for the treatment of moderate to severe pain. A local analgesic effect has been demonstrated, but its mechanism of action remains unclear. METHODS In this study, we examined the effect of local, systemic and nerve block tramadol on the nociceptive flinching behavior elicited by injection of 50 microL of 1% formalin into the dorsal region of hind paw of rats. Nociceptive flinching behavior was observed for 60 minutes. RESULTS Local tramadol in higher concentrations (2.5 and 5 mg) almost eliminated flinching behavior during the entire test. Systemic and neural block tramadol did not affect flinching behavior in phase I and partially decreased it in phase II. CONCLUSIONS Tramadol presented a local analgesic effect in formalin nociceptive flinching behavior that is different from its central analgesic effect. This analgesic effect, in this model, seems not to be linked to a local anesthetic like effect.

Tramadol wound infiltration is not different from intravenous tramadol in children: a randomized controlled trial

STUDY OBJECTIVE The purpose of this trial was to assess if tramadol wound infiltration is superior to intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local anesthetic-like effect. DESIGN Randomized double-blind controlled trial. SETTING Postanesthesia care unit. PATIENTS Forty children, American Society of Anesthesiologists physical status I or II, scheduled to elective inguinal hernia repair. INTERVENTIONS Children were randomly distributed in 1 of 2 groups: IV tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. MEASUREMENTS In the postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue medication, and total rescue morphine and dipyrone consumption. MAIN RESULTS Pain scores measured during the postanesthesia recovery time were similar between groups. Time to first rescue medication was shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was also similar between groups. CONCLUSIONS We concluded that tramadol was effective in reducing postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or somnolence regarding IV route or wound infiltration.

Experimental models for the study of neuropathic pain

JUSTIFICATIVA E OBJETIVOS: Os modelos ideais deveriam reproduzir apenas deficits sensitivos, como alodinea, hiperalgesia e dor espontânea por curtos periodos de tempo. Existem diversos tipos de modelos animais, que avaliam as diversas etiologias e manifestacoes da dor neuropatica. Alguns modelos estudam os mecanismos perifericos e outros estudam mecanismos centrais da dor neuropatica. Esta revisao enfoca os modelos animais mais comumente utilizados para pesquisa em dor neuropatica. CONTEUDO: Sao descritos modelos animais baseados em ligadura de nervos perifericos que sao mais comumente empregados. De todos os modelos descritos nesta revisao, a lesao poupadora de nervo e aquela que produz anormalidades comportamentais mais reprodutiveis, por um periodo mais longo, ao passo que a constricao cronica do ciatico produz sinais comportamentais de neuropatia dolorosas menos previsiveis. Hemiseccao espinhal e lesao espinhal induzida por citocinas sao os modelos de escolha para estudar mecanismos de dor central. Outros modelos especificos sao utilizados para estudo da etiologia especifica da condicao dolorosa. CONCLUSAO: Como a dor neuropatica e multifatorial, diferentes modelos animais de dor neuropatica foram desenvolvidos ao longo dos anos que tem sido fundamentais para o estudo da dor neuropatica, uma vez que muito do conhecimento atual provem de estudos em ratos e camundongos. Sao necessarios maiores refinamentos nos modelos animais atualmente empregados e mais esforcos para determinar quais modelos animais podem ser mais preditivos, com menos vieses e com parâmetros de analises mais complexos e objetivos.

Avaliação da adição do tramadol sobre o tempo de regressão do bloqueio motor induzido pela lidocaína: estudo experimental em ratos

BACKGROUND AND OBJECTIVES: Tramadol blocks somatosensory potentials in vitro and may be associated to local anesthetics to improve analgesic quality. This study aimed at evaluating whether tramadol changes lidocaine motor block regression in two different concentrations. METHOD: Male Wistar rats weighing 250 to 300 g were submitted to sciatic nerve block guided by percutaneous nerve stimulation. Animals were distributed in four groups (n = 5 per group): 2% lidocaine (GI), 0.5% lidocaine (GII), 2% lidocaine/1.25 mg tramadol (GIII), 0.5% lidocaine/1.25 mg tramadol (GIV). Partial and total motor block regression times were evaluated. RESULTS: Al animals had total motor block when awakening from anesthesia, which has totally regressed during the observation period. Total regression time of 2% lidocaine was 41 ± 1.71 minutes, 0.5% lidocaine was 25.26 ± 0.83 minutes, 2% lidocaine/tramadol was 46.06 ± 0.88 minutes and 0.5% lidocaine/tramadol was 36.15 ± 1.18 minutes. The association of 0.5% lidocaine and 1.25 mg tramadol was more effective as compared to 0.5% lidocaine alone. Data are presented in mean ± mean standard error (mse), considering significant p < 0.05 using ANOVA followed by Tukey test. CONCLUSION: Tramadol has effects similar to local anesthetics and, when used as adjuvant of lidocaine, prolongs motor block duration in rats.