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.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus accumbens in rats.

Nucleus accumbens is proposed as one of the centers in the neural circuitry involved in the regulation of feeding and drinking behaviour in rats. Injection of dopamine and angiotensin-II into this nucleus has been documented to affect water and food intake in rats. Reports on the effect of intracerebral injection of catecholamines on feeding and drinking behaviour in animal models are conflicting. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus accumbens on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.3 +/- 0.46 g and 21.7 +/- 1.03 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus accumbens. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus accumbens through the implanted cannulae in different group of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h water intake reaching a maximum of 28.88 +/- 1.45 ml at 1 microgram dose, without change in food intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated water intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus accumbens resulted in a significant and sustained inhibition of water intake (16.61 +/- 0.67 ml) without change in food intake. These observations suggest that noradrenaline facilitates water intake without affecting food intake when injected into the nucleus accumbens in rats and the dipsogenic effect of noradrenaline is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus accumbens in rats.

Corporeal blood gas changes according to duration of drug-induced prolonged erection

The corporeal blood gas changes in accordance with the duration of the prolonged erection which developed after intracorporeal pharmacotherapy with papaverine and phentolamine were investigated in 62 impotence patients. The picture of the corporeal blood taken from 15 psychogenic impotence patients (a control group) at 10 minutes after intracavernous injection when they showed full erections was arterial but there was pCO2 rise and pH drop compared to femoral artery blood taken simultaneously. As the erection lasted longer, significant gas changes of the cavernous blood began to appear (p<0.0001): increase in pCO2 and decrease in pO2 from 4 hours, decrease in pH from 5 hours, decrease in O2 saturation from 6 hours. Erections lasting for more than 16 hours showed significantly worse hypoxia (p<0.05). Therefore, to prevent hypoxia and metabolic acidosis, drug-induced prolonged erection would be better decompressed before it lasts for more than 4 hours.

Participation de alpha receptors in the neural control of food intake in pegeons

The effects of noradrenaline (NA) on food intake were investigated in 69 satiated (food ad libitum) adult pigeons (320-360 g). NA (30 nmol, N = 10, and 80 nmol, N = 12, in 1 µl NaCl) was injected into the right lateral ventricle. Both doses caused a significant increase in food consumption; the higher dose caused a more prolonged effect. The 30-nmol NA injection induced significant increases in the 1st (from 1.6 to 4.5 g) and 6th (19.4 to 25.9g) hours. The 80-nmol dose caused significant increases from the 1st to the 5th hour (1.6 to 6.8,4.4 to 8.7,7.1 to 10.8,10.1 to 14.1 and 14.9 to 21.0g). Previous intracerebroventricular administration of phentolamine (50 nmol, N = 12), but not of propranolol (100 nmol, N= 13) suppressed food ingestion increased by NA administration, with identical results to those of the control group (N = 22). These results indicate that central adrenergic synapses are likely to be involved in the mediation of food intake regulation

Respuesta vascular del Allium sativum (Ajo) en espirales de aorta de ratas antes y después de administrar fentolamina / Vascular response of the Allium sativum (Garlic) in spiral of rats aorta before and after to administer phentolamine

La administración de dosis crecientes (desde 1 x 10 -9) hasta 100 microgramos) del extracto del ajo (Allium sativuN), produjo contracción de los espirales de las aortas aisladas de las ratas. La actividad contráctil del ajo fue proporcional a la dosis utilizada; se produjo una contracción de 17.36 (por ciento) con la dosis más baja utilizada o sea 1 x 10 -9 microgramos. La dosis de 1 x 10 -6 microgramos produjo una contracción aproximada al 50 (por ciento) (57.3 por ciento) y la contracción máxima se produjo con la dosis de 100 microgramos. Las mismas dosis del ajo fueron nuevamente ensayadas, pero esta vez en presencia de 250 microgramos del bloqueador alfa adrenérgico, fentolamina. En este caso se observó una gran inhibición de la respuesta contráctil del ajo, lo que nos denota la aparente actividad alfa adrenérgica del ajo y que sería la responsable de la contractilidad de las aortas de las ratas. En la última parte de la experimentación, se ensayó una sola dosis del ajo 1 x 10 -6 microgramos y una sola dosis de adrenalina 10.1 microgramos antes y después de fentolamina. La fentolamina inhibió las respuestas del ajo y de la adrenalina, lo que nos confirma la actividad agonista alfa de estos compuestos. Se evidencia la gran actividad contráctil que posee el ajo para contraer las aortas de las ratas, sobre todo cuando se compara con la contracción de la adrenalina

Efeitos da fentolamina sobre os volumes cardíacos em cäes / Effects of phentolamine on the cardiac volumes in dogs

No presente trabalho foram usados 10 cäes, visando-se estudar os efeitos da fentolamina sobre os volume cardíacos pelo método da impedância elétrica. Entre 25 e 40 segundos após a administraçäo intravenosa de fentolamina (0,2 mg/Kg de massa corporal), ocorreu uma reduçäo na pressäo arterial e no volume sistólico de reserva, e um aumento no volume de ejeçäo, na capacidade diastólica de reserva e na freqüência cardíaca. Após 20 minutos, o volume de ejeçäo mostrava-se maior do que no período anterior, o volume sistólico de reserva permanecia ainda reduzido, porém, menos que no período anterior, e a capacidade diastólica de reserva näo apresentava variaçäo significativa. Näo houve uma correspondência perfeita entre o uso máximo das reservas sistólicas e o máximo de ejeçäo, provavelmente devido as variaçöes no uso das reservas diastólicas