Elton Constantino

Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos

JUSTIFICATIVA Y OBJETIVOS: Existen evidencias de que el paso de informaciones nociceptivas por el cuerno posterior de la medula espinal (CPME), y que continua hacia niveles rostrales del sistema nervioso central, sufre profundas influencias excitatorias e inhibitorias. La presente investigacion quiso comparar los efectos de la metisergida, de la fentolamina y de la fentolamina asociada a la metisergida, administrados por via subaracnoidea, sobre las fases I, intermedia y II del test de la formalina modificado en ratones. METODO: Fueron utilizados en el experimento, 28 ratones Wistar machos, distribuidos aleatoriamente en cuatro grupos (n = 7), para recibir una solucion salina (GC), fentolamina (GF), metisergida (GM) o fentolamina asociada a la metisergida ((GFM). El dolor fue inducido por la administracion de formalina en la region dorsal de la pata posterior derecha. El test fue dividido en tres fases: fase I, intermedia y fase II. El analisis estadistico de los resultados fue hecho utilizando el programa SPSS (Statistical Package for Social Sciences), [Paquete Estadistico para las Ciencias Sociales], adoptando el nivel de significancia de un 5%. RESULTADOS: En la fase intermedia, el numero de elevaciones de la pata fue significativamente mayor en los grupos GF, GM y GFM cuando se comparo con el grupo GC. CONCLUSIONES: Los resultados nos sugieren la existencia de un efecto noradrenergico y serotoninergico en el sistema inhibitorio descendiente del dolor agudo, con la posibilidad del uso de agonistas serotoninergicos y α1-adrenergicos para el control del dolor agudo.

Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

BACKGROUND AND OBJECTIVES There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified formalin test in rats. METHODS Twenty-eight male Wistar rats distributed randomly in four groups (n=7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of formalin in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5%. RESULTS In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

Efeito anti-inflamatório da suplementação dietética com ácidos graxos ômega-3, em ratos

JUSTIFICATIVA E OBJETIVOS: Diversos estudos tem demonstrado os efeitos beneficos dos acidos graxos omega-3 a saude: no metabolismo lipidico, promovendo reducao nos niveis plasmaticos dos triacilglicerois, aumento de HDL colesterol e, acao anti-inflamatoria ao reduzir a sintese de derivados do acido araquidonico: prostaglandina E2 (PGE2), tromboxano A2 (TXA2), prostaciclina (PGI2) e leucotrieno B4. Portanto, ha de se supor que a suplementacao com acidos graxos EPA e DHA (ω-3), pode atenuar os efeitos do processo inflamatorio a partir da diminuicao da sintese dos eicosanoides, assim como a utilizacao indiscriminada dos anti-inflamatorios. O presente estudo teve como objetivo comparar o efeito analgesico e anti-inflamatorio, entre a suplementacao dietetica com acido graxo omega-3 (ω-3) e tenoxicam em ratos. METODO: Participaram do estudo 18 ratos Wistar machos, pesando entre 220 e 300 g, distribuidos em tres grupos (n = 6): Grupo controle (GC), Grupo tenoxicam (GT) e o Grupo omega-3 (GO) para receberem respectivamente 0,2 mL de solucao fisiologica, 1 mg.kg-1.dia-1 de tenoxicam e 200 mg.kg-1.dia-1 de acido graxo omega-3 diariamente, por gavagem. Apos duas semanas de tratamento, foi realizado o teste da formalina e observacao da resposta nociceptiva, ja que a segunda fase do teste se atribui liberacao de mediadores endogenos locais, que geram resposta inflamatoria local, responsavel pela sensibilizacao de aferentes primarios e de neuronios medulares subsequente a ativacao de nociceptores. A analise estatistica dos resultados obtidos foi realizada utilizando o programa JMP do SAS, adotando o nivel de significância de 5%. RESULTADOS: Os grupos tenoxicam e omega-3 nao apresentaram diferencas estatisticamente significantes quando comparados entre si nas fases do teste da formalina modificado. Nao obstante, apresentaram menor resposta algica, com significância estatistica, na segunda fase do teste da formalina quando comparados com o GC. CONCLUSAO: Os resultados demonstraram efeito anti-inflamatorio comparavel entre o emprego de tenoxicam e a suplementacao dietetica com acido graxo omega-3, sugerindo que o uso da suplementacao dietetica com acido graxo omega-3 podera ser de grande valia, principalmente nos processos cronicos, onde o emprego de anti-inflamatorios nao esteroides se relaciona a maior morbidade principalmente no sistema digestivo e renal.

Efeitos da amitriptilina sobre a modulação da dor aguda, em ratos submetidos à ligadura do nervo ciático

JUSTIFICATIVA E OBJETIVOS: Diversos sistemas de receptores estao envolvidos na modulacao central da dor: noradrenergico, serotoninergico e opioide, entre outros. O objetivo foi estudar os efeitos da amitriptilina sobre a modulacao da dor em ratos, apos ligadura do nervo ciatico. METODO: Foram estudados 24 ratos Wistar, machos, com peso medio de 300g, distribuidos em 5 grupos: (C) controle sem tratamento (n = 4), (LC) submetidos a ligadura do nervo ciatico (n = 5), submetidos a ligadura do nervo ciatico e tratados com: (A) amitriptilina (n = 5), (R) com reserpina (n = 5), (AR) com reserpina + amitriptilina. Todos os animais foram submetidos ao teste da formalina modificado. RESULTADOS: A ligadura do nervo ciatico reduziu a resposta nociceptiva. O tratamento com reserpina nao interferiu com a resposta algica na fase 1 do teste da formalina. A amitriptilina restaurou a resposta algica na fase 1 do teste da formalina, indicando potencializacao da nocicepcao periferica, e reduziu o numero das elevacoes das patas durante a fase intermediaria do teste da formalina, na ausencia ou na presenca de reserpina, indicando potencializacao da resposta da via descendente inibitoria da dor. A ligadura do ciatico reduziu a resposta na fase 2 do teste da formalina. A amitriptilina restaurou a resposta anteriormente observada. CONCLUSAO: O tratamento com amitriptilina e reserpina permite sugerir que no modelo de lesao neural periferica, a noradrenalina participa da transducao do sinal lesivo, na modulacao da via descendente inibitoria da dor e na nocicepcao induzida pelo processo inflamatorio. A participacao dos outros mediadores da resposta inflamatoria e da serotonina deve ser considerada.

Efeito hiperálgico da fentolamina, por via subaracnoidea, em ratos ☆

BACKGROUND AND OBJECTIVES Painful phenomenon is one of the most important and complex experiences. Phentolamine is a non-selective alpha-adrenergic antagonist. The objective of this study was to compare the effect of increasing doses of phentolamine into subarachnoid space in rats in the modulation of painful phenomenon. METHODS 84 male Wistar rats were divided into formalin and plantar incision groups, subdivided into six subgroups (n=7). Control group (CG) received only saline (10μL); active subgroups received phentolamine 10μmg (GF10), 20mg (GF20), 30mg (GF30), 40mg (GF40), and 50g (GF50). In formalin group, pain was induced by injection of 50μL of 2% formalin in dorsal region of right posterior paw. In plantar incision group, pain was induced by plantar incision and evaluated using Von Frey filaments. Induction and maintenance of anesthesia were performed with 3% halothane for catheter placement into subarachnoid space and plantar incision. Statistical analysis was performed using the JMP program from SAS with 5% significance level. RESULTS Phentolamine at doses of 20 and 30g increased the algesic response in the intermediate phase of the formalin test. In plantar incision test, it had hyperalgic effect on first, third, fifth, and seventh days at a dose of 10g and on first, third, and fifth days at a dose of 20g and on fifth day at a dose of 30g. CONCLUSION Subarachnoid administration of phentolamine showed hyperalgesic effect, possibly due to the involvement of different subclasses of alpha-adrenergic receptors in modulating pain pathways.

Palestra e manual sobre tratamento da dor alteraram a prescrição de analgésicos no pós-operatório de cirurgia geral

BACKGROUND AND OBJECTIVES: Analgesic planning to manage acute postoperative pain is critical for its effective control, because if untreated it brings noxious changes to the body. This study aimed at analyzing the change in analgesics prescription in the postoperative period of general surgeries before and after the presentation of a symposium and the distribution of a pain management manual. METHOD: This was a prospective study with 45 patients aged between 18 and 70 years, submitted to general surgeries, to evaluate the effectiveness of postoperative analgesia via the pain numerical scale, and to analyze analgesics prescription before and after a presentation and the distribution of a postoperative pain management manual for assistant, resident and internship physicians of the Surgical Clinic of a medium-sized teaching hospital. RESULTS: Pain intensity in the control group was 3.64 ± 3.2 in the 1st hour, 4.24 ± 2.9 within 12 hours, 4.84 ± 2.2 within 24 hours and 4.08 ± 2.3 within 48 hours. Pain intensity in the post-study group was 2.85 ± 2.8 in 1 hour, 2.90 ± 2.7 within 12 hours, 2.25 ± 2.6 within 24 hours and 1.95 ± 2.4 within 48 hours. There has been no statistically significant difference among different hours for the same group, however there has been a difference between the 24th hour of the control group as compared to the study group (p < 0.001) and between the 48th hour of the control group as compared to the study group (p < 0.005). CONCLUSION: The proposed intervention has generated mild changes in postoperative analgesics prescription, however enough to provide pain intensity decrease in some studied moments.

Ação da fluoxetina sobre a dor aguda em ratos submetidos à constrição do nervo ciático

BACKGROUND AND OBJECTIVES: Selective serotonin reuptake inhibitors, such as fluoxetine, have been suggested as alternative to tricyclic antidepressants to treat chronic pain, due to the lower incidence of side effects. This study aimed at observing the effects of serotonin on acute pain modulation, by the administration of fluoxetine through the formalin test in rats previously submitted to sciatic nerve constriction. METHOD: We used 24 male Wistar rats, with mean weight of 300 g and distributed in 5 groups: 1. Control untreated; 2. Sciatic nerve constriction; 3. Sciatic nerve constriction and treated with 5 mg.kg-1.day oral fluoxetine for 15 days; 4. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours and with 5 mg.kg-1.day oral fluoxetine for 15 days; 5. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours for 15 days. All animals were submitted to modified formalin test after treatment. RESULTS: Response in the phase I, intermediate and phase II formalin test was not changed by sciatic nerve constriction. Treatment with reserpine or fluoxetine has not interfered with first and intermediate formalin test phases in the groups submitted to sciatic nerve constriction. The number of flinches in the second formalin test phase has increased in animals treated with fluoxetine and has decreased in animals treated with reserpine. There has been decrease in the number of flinches in animals treated with the association reserpina and fluoxetine as compared to animals treated with fluoxetine alone. CONCLUSION: Fluoxetine has increased painful sensation after acute stimulation in rats submitted to sciatic nerve constriction, showing the algogenic action of the drug in this experimental model.