Adriana Machado Issy

Cytokines and Pain

BACKGROUND AND OBJECTIVES Cytokines are necessary for the inflammatory response, favoring proper wound healing. However, exaggerated proinflammatory cytokine production can manifest systemically as hemodynamic instability or metabolic derangements. The objective of this review was to describe the effects of cytokines in pain. CONTENTS This article reviews the effects of cytokines in pain. In diseases with acute or chronic inflammation, cytokines can be recognized by neurons and used to trigger several cell reactions that influence the activity, proliferation, and survival of immune cells, as well as the production and activity of other cytokines. Cytokines can be proinflammatory and anti-inflammatory. Proinflammatory cytokines are related with the pathophysiology of pain syndromes. Cells that secrete proinflammatory (IL-1, IL-2, IL-6, IL-7, and TNF) and anti-inflammatory (IL-4, IL-10, IL-13, and TGFβ) cytokines, the functions of each cytokine, and the action of those compounds on pain processing, have been described. CONCLUSIONS Cytokines have an important role in pain through different mechanisms in several sites of pain transmission pathways.

Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study

CONTEXT AND OBJECTIVE the role of immune response and proinflammatory cytokines in the pathogenesis of chronic pain has been of growing interest. In order to evaluate whether there is any association between disc herniation and elevated cytokine levels, we measured cytokine levels in patients with chronic low back pain and in healthy subjects. DESIGN AND SETTING analytical cross-sectional study at the Pain Clinic of Universidade Federal da Bahia (UFBA). METHODS cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique on 23 patients with low back pain (G1) and on 10 healthy subjects (G2). RESULTS the levels of tumor necrosis factor-alpha [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0.01) and interleukin-6 [IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0.01) were higher in G1. There were no statistically significant differences in relation to interleukin-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) or soluble tumor necrosis factor receptor [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0.87). CONCLUSION The patients with chronic low back pain due to disc herniation presented higher levels of TNF-alpha and IL-6, but not of IL-1 or sTNF-R.

Review of the use of gabapentin in the control of postoperative pain

BACKGROUND AND OBJECTIVES Gabapentin has been used as adjuvant in the treatment of postoperative pain with a neuropathic component. It is responsible for the inhibition of central sensitization, decreasing postoperative pain. CONTENTS All clinical, randomized studies that evaluated the effects of gabapentin on postoperative pain in humans between 2002 and 2007 for a total of 26 studies were selected. In 17 studies, patients received a single preoperative dose, which ranged from 300 to 1,200 mg, 30 minutes to two hours before surgery in the remaining studies, the administration of the drug was initiated one to 24 hours before the procedure and continued for 10 days, in doses that ranged from 1,200 to 1,800 mg.day(-1). To measure pain severity, the Visual Analog or Numeric Rating Scale was used. In 75% of patients who received a single dose of gabapentin, scores were lower, and the same was seen in 55.6% of patients who received the drugs pre- and postoperatively. Opioid consumption was reduced in 82.4% of patients who received a single dose, and in 77.8% of patients who received pre- and postoperative gabapentin. Among the studies using a single dose of gabapentin, four did not describe adverse effects; 52.9% showed no differences, 11.8% detected more nausea or vomiting, 5.9% experienced more dizziness, 5.9% more sedation, less nausea or vomiting in one, and less urinary retention in one. Among the studies with pre- and postoperative administration of gabapentin, four did not describe adverse effects; 22.2% showed no differences, 11.1% had more nausea or vomiting, 22.2% more dizziness, and 11.1% more sedation. CONCLUSIONS Gabapentin, used before as well as before and after surgery, decreased pain severity and the need of analgesic supplementation.JUSTIFICATIVA Y OBJETIVOS: La gabapentina ha sido utilizada como adyuvante en el tratamiento del dolor postoperatorio con componente neuropatico. Es responsable de la inhibicion de la sensibilizacion central, disminuyendo el dolor postoperatorio. CONTENIDO: Fueron seleccionados todos los estudios clinicos con distribucion aleatoria que evaluaron el efecto de la gabapentina en el dolor postoperatorio en humanos entre 2002 y 2007. Se encontraron 26 articulos publicados. En 17 estudios, los pacientes recibieron dosis unica preoperatoria que vario entre 300 y 1200mg y entre 30min y dos horas antes de los procedimientos. En los demas estudios, la medicacion fue iniciada entre una y 24 horas antes de los procedimientos, y continuada por dos a 10 dias en la dosis de 1.200 a 1.800 mg.dia-1. Para una medida de intensidad del dolor, fueron utilizadas la Escala Analogica Visual o Numerica. En un 75% entre los que recibieron solamente la dosis pre, los puntajes fueron menores con el uso de la gabapentina y tambien en un 55,6% entre los que recibieron dosis pre y pos. El consumo de opioide fue menor en un 82,4% de los que recibieron dosis pre y en un 77,8% en los que recibieron pre y pos. En estudios que usaron pre, cuatro no arrojaron efectos adversos; no hubo diferencia en un 52,9%, mas nausea o vomito en un 11,8%, mas mareos en un 5,9%, mas sedacion en un 5,9%, menos nausea o vomito en uno y menos retencion urinaria en uno. En estudios que usaron pre y pos, cuatro no arrojaron efectos adversos; no hubo diferencia en un 22,2%, mas nausea o vomito en 11,1%, mas mareo en 22,2% y mas sedacion en un 11,1%. CONCLUSIONES: La gabapentina usada tanto antes, como antes y despues de la operacion, promueve la reduccion de la intensidad del dolor y de la necesidad de complementacion analgesica.

Lidocaína por via venosa intraoperatória

JUSTIFICATIVA E OBJETIVOS: Grande parte dos pacientes submetidos a operacao experimentam dor moderada a intensa, havendo necessidade de melhorar a tecnica analgesica. A lidocaina tem sido usada amplamente por via venosa para tratamento de dor cronica. O objetivo foi fazer uma revisao sobre o uso de lidocaina por via venosa para analgesia pos-operatoria. CONTEUDO: Foi realizada revisao dos aspectos farmacologicos da lidocaina, dos mecanismos de acao desse anestesico local e de estudos clinicos nos quais os autores empregaram lidocaina intraoperatoria. CONCLUSOES: A lidocaina venosa pode promover efeito analgesico para procedimentos cirurgicos, sendo mais uma alternativa para o tratamento da dor aguda. A realizacao de mais estudos controlados com diferentes intervencoes operatorias podera trazer mais informacoes sobre essa modalidade analgesica.

Proinflammatory cytokines in patients with neuropathic pain treated with Tramadol

JUSTIFICATIVA Y OBJETIVOS: Las interleucinas proinflamatorias tienen una funcion importante en la fisiopatologia de los sindromes dolorosos neuropaticos. El objetivo de este estudio, fue evaluar los niveles plasmaticos de interleucinas proinflamatorias antes y despues del tratamiento con tramadol en pacientes con hernia de disco y sindrome del tunel del carpo, y compararlos con individuos normales. METODO: Se investigaron 38 pacientes con dolor neuropatico por hernia de disco o sindrome del tunel del carpo. Todos los pacientes fueron tratados con tramadol de liberacion controlada (100 mg en 12h) durante 10 dias. Se realizaron muestras de sangre venosa (5 mL), por la manana, antes del tratamiento y en el 11o dia, y las mismas se almacenaron para ser analizadas (-70oC). Se utilizaron test enzimaticos ELISA para la dosificacion de las interleucinas plasmaticas (TNF-±, IL-1, IL-6) y receptores sTNF-R1, (R & D Systems). Se realizo la dosificacion de interleucinas en suero de 10 voluntarios sanos. RESULTADOS: La concentracion de TNF-± antes (5,8 ± 2,8 pg.mL-1) fue significativamente mayor que despues del tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Test de Mann-Whitney). No hubo diferencia significativa de IL-1², IL-6 y sTNF-R1 antes y despues del tratamiento. Las concentraciones plasmaticas de TNF-± (sanos: 1,4 ± 0,5; pacientes con dolor: 5,8 ± 2,8 pg.mL-1; p = 0.01) y IL-6 (sanos: 1,2 ± 0,8; pacientes con dolor: 3.5 ± 2,6 pg.mL-1; p = 0,01) fueron significativamente mayores en los pacientes con dolor neuropatico que en los voluntarios, test de Mann-Whitney. CONCLUSIONES: En los pacientes con hernia discal y sindrome del tunel del carpo, las concentraciones plasmaticas de TNF-± y IL-6, fueron mas elevadas que en los voluntarios sanos, no habiendo ninguna diferencia en las concentraciones de sTNF-R y IL-1². Hubo una reduccion de la concentracion plasmatica de TNF-±; despues del tratamiento con tramadol (100 mg en 12h), pero no de IL-6 sTNF-R y IL-1².BACKGROUND AND METHODS Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals. METHODS Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70 degrees C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-+/-, IL-1, IL-6) and receptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined. RESULTS The concentration of TNF-+/- before (5.8 +/- 2.8 pg.mL-(1)) was significantly higher than after treatment with tramadol (4.8 +/- 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1(2), IL-6, and sTNF-R1 before and after treatment with tramadol showed no significant differences. Plasma levels of TNF-+/- (healthy individuals: 1.4 +/- 0.5; pain patients: 5.8 +/- 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 +/- 0.8; pain patients: 3.5 +/- 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test. CONCLUSIONS In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-+/- and IL-6 were higher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1(2) were not observed. Plasma levels of TNF-+/-, but not of IL-6, sTNF-R, and IL-1(2), decreased after treatment with tramadol (100 mg every 12 hours).

Revisão sobre o uso de gabapentina para controle da dor pós-operatória

BACKGROUND AND OBJECTIVES Gabapentin has been used as adjuvant in the treatment of postoperative pain with a neuropathic component. It is responsible for the inhibition of central sensitization, decreasing postoperative pain. CONTENTS All clinical, randomized studies that evaluated the effects of gabapentin on postoperative pain in humans between 2002 and 2007 for a total of 26 studies were selected. In 17 studies, patients received a single preoperative dose, which ranged from 300 to 1,200 mg, 30 minutes to two hours before surgery in the remaining studies, the administration of the drug was initiated one to 24 hours before the procedure and continued for 10 days, in doses that ranged from 1,200 to 1,800 mg.day(-1). To measure pain severity, the Visual Analog or Numeric Rating Scale was used. In 75% of patients who received a single dose of gabapentin, scores were lower, and the same was seen in 55.6% of patients who received the drugs pre- and postoperatively. Opioid consumption was reduced in 82.4% of patients who received a single dose, and in 77.8% of patients who received pre- and postoperative gabapentin. Among the studies using a single dose of gabapentin, four did not describe adverse effects; 52.9% showed no differences, 11.8% detected more nausea or vomiting, 5.9% experienced more dizziness, 5.9% more sedation, less nausea or vomiting in one, and less urinary retention in one. Among the studies with pre- and postoperative administration of gabapentin, four did not describe adverse effects; 22.2% showed no differences, 11.1% had more nausea or vomiting, 22.2% more dizziness, and 11.1% more sedation. CONCLUSIONS Gabapentin, used before as well as before and after surgery, decreased pain severity and the need of analgesic supplementation.JUSTIFICATIVA Y OBJETIVOS: La gabapentina ha sido utilizada como adyuvante en el tratamiento del dolor postoperatorio con componente neuropatico. Es responsable de la inhibicion de la sensibilizacion central, disminuyendo el dolor postoperatorio. CONTENIDO: Fueron seleccionados todos los estudios clinicos con distribucion aleatoria que evaluaron el efecto de la gabapentina en el dolor postoperatorio en humanos entre 2002 y 2007. Se encontraron 26 articulos publicados. En 17 estudios, los pacientes recibieron dosis unica preoperatoria que vario entre 300 y 1200mg y entre 30min y dos horas antes de los procedimientos. En los demas estudios, la medicacion fue iniciada entre una y 24 horas antes de los procedimientos, y continuada por dos a 10 dias en la dosis de 1.200 a 1.800 mg.dia-1. Para una medida de intensidad del dolor, fueron utilizadas la Escala Analogica Visual o Numerica. En un 75% entre los que recibieron solamente la dosis pre, los puntajes fueron menores con el uso de la gabapentina y tambien en un 55,6% entre los que recibieron dosis pre y pos. El consumo de opioide fue menor en un 82,4% de los que recibieron dosis pre y en un 77,8% en los que recibieron pre y pos. En estudios que usaron pre, cuatro no arrojaron efectos adversos; no hubo diferencia en un 52,9%, mas nausea o vomito en un 11,8%, mas mareos en un 5,9%, mas sedacion en un 5,9%, menos nausea o vomito en uno y menos retencion urinaria en uno. En estudios que usaron pre y pos, cuatro no arrojaron efectos adversos; no hubo diferencia en un 22,2%, mas nausea o vomito en 11,1%, mas mareo en 22,2% y mas sedacion en un 11,1%. CONCLUSIONES: La gabapentina usada tanto antes, como antes y despues de la operacion, promueve la reduccion de la intensidad del dolor y de la necesidad de complementacion analgesica.

Citocinas e dor

JUSTIFICATIVA Y OBJETIVOS: Las citocinas son sustancias necesarias para la respuesta inflamatoria, favoreciendo la cicatrizacion apropiada de la herida. Sin embargo, la produccion exagerada de citocinas proinflamatorias a partir de la lesion puede manifestarse sistemicamente con la inestabilidad hemodinamica o disturbios metabolicos. El objetivo de esta revision fue describir los efectos de las citocinas en el dolor. CONTENIDO: Este articulo intenta hacer una revision de los efectos de las citocinas en el dolor. En enfermedades que se manifiestan con un proceso inflamatorio agudo o cronico, las citocinas pueden ser reconocidas por las neuronas y utilizadas para desencadenar diversas reacciones celulares que influyen en la actividad, proliferacion y sobrevida de la celula inmunologica, como tambien en la produccion y en la actividad de otras citocinas. Las citocinas pueden ser proinflamatorias y antiinflamatorias. Las proinflamatorias tienen una relacion con la fisiopatologia de los sindromes dolorosos. Ya se han descrito las celulas que segregan las citocinas, las citocinas proinflamatorias (IL-1, IL-2, IL-6, IL-7 y FNT) y antiinflamatorias (IL-4, IL-10, IL-13 y FTCβ), las funciones de cada citocina y tambien como ocurre la accion de esas sustancias en el proceso del dolor. CONCLUSIONES: Las citocinas desempenan un rol muy importante en el dolor, actuando por medio de diferentes mecanismos en varios locales de las vias de transmision del dolor.

Citocinas pró-inflamatórias em pacientes com dor neuropática submetidos a tratamento com Tramadol

JUSTIFICATIVA Y OBJETIVOS: Las interleucinas proinflamatorias tienen una funcion importante en la fisiopatologia de los sindromes dolorosos neuropaticos. El objetivo de este estudio, fue evaluar los niveles plasmaticos de interleucinas proinflamatorias antes y despues del tratamiento con tramadol en pacientes con hernia de disco y sindrome del tunel del carpo, y compararlos con individuos normales. METODO: Se investigaron 38 pacientes con dolor neuropatico por hernia de disco o sindrome del tunel del carpo. Todos los pacientes fueron tratados con tramadol de liberacion controlada (100 mg en 12h) durante 10 dias. Se realizaron muestras de sangre venosa (5 mL), por la manana, antes del tratamiento y en el 11o dia, y las mismas se almacenaron para ser analizadas (-70oC). Se utilizaron test enzimaticos ELISA para la dosificacion de las interleucinas plasmaticas (TNF-±, IL-1, IL-6) y receptores sTNF-R1, (R & D Systems). Se realizo la dosificacion de interleucinas en suero de 10 voluntarios sanos. RESULTADOS: La concentracion de TNF-± antes (5,8 ± 2,8 pg.mL-1) fue significativamente mayor que despues del tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Test de Mann-Whitney). No hubo diferencia significativa de IL-1², IL-6 y sTNF-R1 antes y despues del tratamiento. Las concentraciones plasmaticas de TNF-± (sanos: 1,4 ± 0,5; pacientes con dolor: 5,8 ± 2,8 pg.mL-1; p = 0.01) y IL-6 (sanos: 1,2 ± 0,8; pacientes con dolor: 3.5 ± 2,6 pg.mL-1; p = 0,01) fueron significativamente mayores en los pacientes con dolor neuropatico que en los voluntarios, test de Mann-Whitney. CONCLUSIONES: En los pacientes con hernia discal y sindrome del tunel del carpo, las concentraciones plasmaticas de TNF-± y IL-6, fueron mas elevadas que en los voluntarios sanos, no habiendo ninguna diferencia en las concentraciones de sTNF-R y IL-1². Hubo una reduccion de la concentracion plasmatica de TNF-±; despues del tratamiento con tramadol (100 mg en 12h), pero no de IL-6 sTNF-R y IL-1².BACKGROUND AND METHODS Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals. METHODS Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70 degrees C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-+/-, IL-1, IL-6) and receptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined. RESULTS The concentration of TNF-+/- before (5.8 +/- 2.8 pg.mL-(1)) was significantly higher than after treatment with tramadol (4.8 +/- 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1(2), IL-6, and sTNF-R1 before and after treatment with tramadol showed no significant differences. Plasma levels of TNF-+/- (healthy individuals: 1.4 +/- 0.5; pain patients: 5.8 +/- 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 +/- 0.8; pain patients: 3.5 +/- 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test. CONCLUSIONS In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-+/- and IL-6 were higher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1(2) were not observed. Plasma levels of TNF-+/-, but not of IL-6, sTNF-R, and IL-1(2), decreased after treatment with tramadol (100 mg every 12 hours).

Cetamina e analgesia preemptiva

JUSTIFICATIVA Y OBJETIVOS: Desde la descubierta de que la cetamina bloquea los receptores NMDA en los neuronios del cuerno dorsal de la medula, ella ha sido usada para inhibir o reducir la sensibilizacion central provocada por estimulos nociceptivos. Asi, este trabajo tiene por finalidad mostrar aspectos farmacologicos de la cetamina racemica y de su compuesto levogiro y su empleo en la analgesia preemptiva. CONTENIDO: Se presentan conceptos actuales sobre analgesia preemptiva, aspectos farmacologicos de la cetamina y su derivado levogiro, bien como estudios experimentales y clinicos sobre la cetamina y su uso en analgesia preemptiva. CONCLUSIONES: Aun no esta totalmente comprobada la eficacia de la cetamina en inhibir o reducir la sensibilizacion central provocada por estimulos nociceptivos. Probablemente eso se deba al uso de diferentes metodos de estudio y de analisis estadistica.

Effect of intravenous lidocaine associated with amitriptyline on pain relief and plasma serotonin, norepinephrine, and dopamine concentrations in fibromyalgia.

ObjectiveThe objective of this study was to evaluate the effect of intravenous lidocaine combined with amitriptyline on pain relief and plasma serotonin, norepinephrine, and dopamine levels. MethodsA prospective, randomized, double-blind comparative study was conducted in 30 patients. All patients received 25 mg amitriptyline; monotherapy group (n=15) received 125 mL saline, and combined therapy group (n=15) received 240 mg lidocaine in 125 mL saline once a week for 4 weeks. Serotonin, norepinephrine, and dopamine were measured in plasma at time zero (T0) and after 4 weeks (T4). Pain intensity was rated on a numerical scale at the beginning of the study and weekly for 4 weeks. ResultsAll patients were females and the mean age was 44.7±10.5 years for monotherapy group and 40.9±11.6 years for combined therapy group. No difference in pain intensity at baseline was observed between groups, with a decrease after treatment in monotherapy group (T0: 7.0±1.2 and T4: 4.0±2.1) and in combined therapy group (T0: 7.6±0.8 and T4: 4.1±2.3). Plasma serotonin and norepinephrine levels were similar in the 2 groups at T0 and T4. An increase in dopamine levels was observed in monotherapy group from the beginning to the end of treatment. ConclusionsCombined administration of 240 mg intravenous lidocaine (once a week) and 25 mg amitriptyline for 4 weeks did not modify pain intensity or plasma serotonin, norepinephrine, or dopamine concentrations in fibromyalgia patients.