Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos / Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

JUSTIFICATIVA E OBJETIVOS: Há evidências de que a passagem de informações nociceptivas pelo corno posterior da medula espinhal (CPME) seguindo para níveis rostrais do sistema nervoso central sofre profundas influências excitatórias e inibitórias. A presente pesquisa teve como objetivo comparar os efeitos da metissergida, da fentolamina e da fentolamina associada à metissergida, administrados por via subaracnoidea, sobre as fases I, intermediária e II do teste da formalina modificado em ratos. MÉTODO: Foram utilizados 28 ratos Wistar machos, distribuídos aleatoriamente em quatro grupos (n = 7) para receber solução salina (GC), fentolamina (GF), metissergida (GM) ou fentolamina associada à metissergida (GFM) por via subaracnoidea. A dor foi induzida pela administração de formalina na região dorsal da pata posterior direita. O teste foi dividido em três fases; fase I, intermediária e fase II. A análise estatística dos resultados foi realizada utilizando o programa SPSS (Statistical Package for Social Sciences), adotando o nível de significância de 5 por cento. RESULTADOS: Na fase intermediária, o número de elevações da pata foi significativamente maior nos grupos GF, GM e GFM quando comparados com o grupo GC. CONCLUSÕES: Os resultados sugerem a existência de efeito noradrenérgico e serotoninérgico no sistema inibitório descendente da dor aguda, com a possibilidade de emprego de agonistas serotoninérgicos e α1-adrenérgicos para controle da dor aguda.

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 phormaline 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 phormaline 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 percent. 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.

JUSTIFICATIVA Y OBJETIVOS: Existen evidencias de que el paso de informaciones nociceptivas por el cuerno posterior de la médula espinal (CPME), y que continúa hacia niveles rostrales del sistema nervioso central, sufre profundas influencias excitatorias e inhibitorias. La presente investigación quiso comparar los efectos de la metisergida, de la fentolamina y de la fentolamina asociada a la metisergida, administrados por vía subaracnoidea, sobre las fases I, intermedia y II del test de la formalina modificado en ratones. MÉTODO: Fueron utilizados en el experimento, 28 ratones Wistar machos, distribuidos aleatoriamente en cuatro grupos (n = 7), para recibir una solución salina (GC), fentolamina (GF), metisergida (GM) o fentolamina asociada a la metisergida ((GFM). El dolor fue inducido por la administración de formalina en la región dorsal de la pata posterior derecha. El test fue dividido en tres fases: fase I, intermedia y fase II. El análisis estadístico de los resultados fue hecho utilizando el programa SPSS (Statistical Package for Social Sciences), [Paquete Estadístico para las Ciencias Sociales], adoptando el nivel de significancia de un 5 por ciento. RESULTADOS: En la fase intermedia, el número de elevaciones de la pata fue significativamente mayor en los grupos GF, GM y GFM cuando se comparó con el grupo GC. CONCLUSIONES: Los resultados nos sugieren la existencia de un efecto noradrenérgico y serotoninérgico en el sistema inhibitorio descendiente del dolor agudo, con la posibilidad del uso de agonistas serotoninérgicos y α1-adrenérgicos para el control del dolor agudo.

The Mechanism of Antiallodynic Effect of Intrathecal Morphine in Neuropathic Pain Induced by Spinal Nerve Ligation: The Effect of Methysergide and Theophylline / 대한마취과학회지

BACKGROUND: Although the efficacy of morphine in a neuropathic pain state is somewhat controversial, spinally administered morphine reversed the tactile allodynia in a previous animal study. Using a behaviorial test, we examined the involvement of serotonergic and adenosine receptors in the mechanism of the antiallodynic action of the intrathecal morphine by injection of serotonergic and adenosine antagonist in a rat model of neuropathic pain induced by a spinal nerve ligation. METHODS: Male Sprague-Dawley rats were prepared with a tight ligation of the left lumbar 5th and 6th spinal nerve and a chronic lumbar intrathecal catheter implantation. Morphine 1 microgram was administered intrathecally to attenuate the tactile allodynia. Methysergide 10 microgram and 30 microgram, theophylline 20 microgram was administered intrathecally before and after the injection of morphine in order to investigate the reversal of an increased allodynic threshold by morphine. The allodynic thresholds for the left hindpaw withdrawl to von Frey hairs were assessed and converted to %MPE. RESULTS: The tactile allodynic threshold was significantly increased by 1 microgram of intrathecal morphine (P < 0.05). Methysergide 10 microgram and 30 microgram, but not theophylline 20 microgram, reversed significantly the antiallodynic effect of intrathecal morphine in pre- and post-treatment (P < 0.05). CONCLUSIONS: The results suggested that the mechanism of tactile antiallodynia induced by intrathecal morphine appears to be mediated by serotonin receptor system at the spinal level in the rat model of spinal nerve ligation.

Effects of Methysergide on Serum Growth Hormone Response after Electroconvulsive Therapy / 대한정신약물학회지

OBJECTIVES: The purpose of this study was to investigate the effects of methysergide(serotonin receptor antagonist) on serum growth hormone response after electroconvulsive therapy(ECT). METHODS: We studied the changes of the serum growth hormone levels of the day before ECT(No ECT), ECT without methysergide pretreatment(ECT alone), and ECT with methysergide pretreatment(M+ECT) by radioimmunoassay method in 14 psychiatric patients. ECT was induced by the application of 110 volts for a period 0.3-1.0 second, using bitemporal electrodes. RESULTS: 1) Serum growth hormone levels at 15, 30, and 60 minutes after ECT were significantly increased in the ECT alone group than in the No ECT group(p<0.05). 2) Serum growth hormone levels at 15, 30, and 60 minites after ECT were significantly decreased in the M+ECT group than in the ECT alone group(p<0.05). CONCLUSION: These results suggest that the response of growth hormone after ECT seems to be mediated by the activation of serotonergic system.