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.

Role of 5HT in the modification of intestinal motility, in vitro study

To determine with the mechanism of action involved in the therapeutic potential of serotonin and its blocker on gastrointestinal motility. The standard method was used for obtaining the longitudinal and circular muscles strip of rabbit ileum for in vitro studies. Each muscle strip was exposed to serotonin and its blocker and the result obtained was recorded on polygraph apparatus. The effects were recorded in vice versa fashion i.e. agonist v/s antagonist and antagonist v/s agonist on longitudinal and circular muscle strip separately. Serotonin had depressant effect on the force of contraction. On addition of antagonist in the presence of agonist, the effects were increased. Longitudinal muscle showed more pronounced effect i.e. 52.7% with methysergide in comparison to circular muscle, which was 15.6%. Circular muscle showed reduction in the force of contraction with serotonin, which was increased on addition of antagonist, but still below the level of base line contraction. Serotonin when given from external source in vitro, decreased the force, however, there was minimal increase in the rate of contraction. Hence, serotonin decreases the intestinal motility giving an impression of having antispasmodic effect. The results of this study can be utilized in the development of new drug related to G.I. motility mediated through 5HT receptors

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

The antinociceptive effects of stimulating the medial (ME) and central (CE) nuclei of the amygdala in rats were evaluated by the changes in the latency for the tail withdrawal reflex to noxious heating of the skin. A 30-s period of sine-wave stimulation of the ME or CE produced a significant and short increase in the duration of tail flick latency. A 15-s period of stimulation was ineffective. Repeated stimulation of these nuclei at 48-h intervals produced progressively smaller effects. The antinociception evoked from the ME was significantly reduced by the previous systemic administration of naloxone, methysergide, atropine, phenoxybenzamine, and propranolol, but not by mecamylamine, all given at the dose of 1.0 mg/kg. Previous systemic administration of naloxone, atropine, and propranolol, but not methysergide, phenoxy-benzamine, or mecamylamine, was effective against the effects of stimulating the CE. We conclude that the antinociceptive effects of stimulating the ME involve at least opioid, serotonergic, adrenergic, and muscarinic cholinergic descending mechanisms. The effects of stimulating the CE involve at least opioid, beta-adrenergic, and muscarinic cholinergic descending mechanisms.

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (P

Effect of graded doses of methysergide on basal and pentagastrin stimulated gastric secretion in anaesthetised rats.

The effect of continuous infusion (iv) of graded doses of methysergide (0.1-50 microgram(s)/kg/hr) was studied on basal and pentagastrin (5 microgram(s)/kg/hr) stimulated gastric acid secretion in anaesthetised rats by the slow, continuous stomach perfusion method. Both basal and pentagastrin stimulated acid secretion indicated a biphasic response. Methysergide induced stimulation at a lower dose of 1 microgram(s)/kg/hr and inhibition at higher doses of 20-50 microgram(s)/kg/hr. The stimulatory effect may be due to postsynaptic receptor blockade while the inhibitory effect at higher dose may be due to blockade of presynaptic 5-HT autoreceptors, or due to a direct inhibitory effect of unknown basis.

Effect of monoamine antagonists on pretectal evoked analgesia in rat.

Mild and brief electrical stimulation of sites in the pretectal nucleus of rat produced analgesia (SPA) of long duration without significant aversion. Intracerebroventricular (icv) administration of 5-HT receptor antagonists methysergide (50 micrograms) and ketanserin (50 micrograms) and the dopaminergic antagonist haloperidol (50 micrograms) had no significant effect on pretectal SPA, but alpha and beta adrenoceptor antagonists phenoxybenzamine (50 micrograms) and sotalol (50 micrograms) on icv injection significantly antagonised the pretectal SPA. The results suggest that pretectal SPA involves activation of central adrenoceptors.

Effect of exogenous 5-hydroxytryptamine on pathogenicity of Entamoeba histolytica in experimental animals.

In an effort to find out the mechanism(s) operative in enhancing the pathogenicity of E. histolytica in hosts under heat stress reported earlier, effect of 5-hydroxytryptamine (5-HT) on the virulence of the parasite was examined in just weaned Charles Foster strain of albino rats. Pathogenicity of 10 strains of E. histolytica, from various forms of intestinal amoebiasis, grown in modified Boeck and Drbohlav's medium was assessed by caecal scoring. Administration of 5-HT in infected animals significantly enhanced the pathogenicity of all the seven strains tested. Treatment of the host with the 5-HT precursor L-tryptophan also increased the caecal scores examined with three strains of E. histolytica. Prior blocking of tissue 5-HT receptors by administration of methysergide almost completely abolished the pathogenicity enhancing effect of 5-HT treatment. This suggested that 5-HT itself and not any of its metabolites was responsible for the observed increase in pathogenicity of E. histolytica on 5-HT treatment of the host.

Effect of drugs influencing central 5-hydroxytryptamine mechanisms on amantadine-induced stereotyped behaviour in the rat.

Pretreatment with L-tryptophan, a precursor of 5-HT, was found to decrease the intensity of stereotyped behaviour induced by amantadine, while methysergide, a 5-HT antagonist, was found to increase the intensity of amantadine-induced stereotypy. These results suggest that the intensity of amantadine-induced stereotypy depends on the balance between central dopamine and 5-HT systems and that the central 5-HT systems may have an opposing, tonic effect upon central dopamine systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a 5-HT agonist, and clomipramine, a selective 5-HT neuronal reuptake blocker, was found to potentiate the stereotyped behaviour induced by amantadine.