RESUMEN
The dorsal raphe nucleus (DRN) is a key structure of the endogenous pain inhibitory system. Although the DRN is rich in serotoninergic neurons, cholinergic neurons are also found in that nucleus. Both ictal and inter-ictal states are followed by post-ictal analgesia. The present study investigated the role of cholinergic mechanisms in postictal antinociceptive processes using microinjections of atropine and mecamylamine, muscarinic and nicotinic cholinergic receptor antagonists, respectively, in the DRN of rats. Intraperitoneal injection of pentylenetetrazole (PTZ) (at 64mg/kg) caused tonic and tonic-clonic seizures. The convulsive motor reactions were followed by an increase in pain thresholds, a phenomenon known as post-ictal analgesia. Pre-treatment of the DRN with atropine or mecamylamine at 1µg, 3µg and 5µg/0.2µL decreased the post-ictal antinociceptive phenomenon. The present results showed that the post-ictal analgesia was mediated by muscarinic and nicotinic cholinergic receptors in the DRN, a structure crucially involved in the neural network that organises post-ictal hypoalgesia.
Asunto(s)
Núcleo Dorsal del Rafe/fisiopatología , Umbral del Dolor/efectos de los fármacos , Receptores Muscarínicos/fisiología , Receptores Nicotínicos/fisiología , Transmisión Sináptica/fisiología , Acetilcolina/farmacología , Analgésicos/farmacología , Animales , Atropina/farmacología , Núcleo Dorsal del Rafe/efectos de los fármacos , Epilepsia Tónico-Clónica/metabolismo , Epilepsia Tónico-Clónica/fisiopatología , Neuronas GABAérgicas/metabolismo , Masculino , Mecamilamina/farmacología , Antagonistas Muscarínicos/farmacología , Antagonistas Nicotínicos/farmacología , Dimensión del Dolor/métodos , Umbral del Dolor/fisiología , Ratas , Ratas Wistar , Neuronas Serotoninérgicas/fisiología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Pentylenetetrazol (PTZ), a non-competitive antagonist that blocks GABA-mediated Cl(-) flux, was used in the present work to induce seizures in animals. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significative increase in the tail-flick latencies (TFL), for at least 120 min of the post-ictal period. Peripheral administration of naltrexone (5 mg/kg, 10 mg/kg and 20 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. These data were corroborated with peripheral administration of naloxonazine (10 mg/kg and 20 mg/kg), a mu(1)-opioid blocker, in the same doses used for non-specific antagonist. These results indicate that endogenous opioids may be involved in the post-ictal analgesia. The involvement of mu(1)-opioid receptor was also considered.