Freitas Renato Leonardo, Bassi Gabriel Shimizu, de Oliveira Ana Maria, Coimbra Norberto Cysne
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
Exp Neurol. 2008 Oct;213(2):410-8. doi: 10.1016/j.expneurol.2008.07.003. Epub 2008 Jul 11.
The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. Pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl(-) influx antagonist, was peripherally used to induce tonic-clonic seizures in Wistar rats. The nociceptive threshold was measured by the tail-flick test. Neurochemical lesions of the DRN, performed with microinjection of ibotenic acid (1.0 microg/0.2 microL), caused a significant decrease of tonic-clonic seizure-induced antinociception, suggesting the involvement of this nucleus in this antinociceptive process. Microinjections of methysergide (1.0 and 5.0 microg/0.2 microL), a non-selective serotonergic receptor antagonist, into DRN caused a significant decrease in the post-ictal antinociception in seizing animals, compared to controls, in all post-ictal periods presently studied. These findings were corroborated by microinjections of ketanserin (at 1.0 and 5.0 microg/0.2 microL) into DRN. Ketanserin is an antagonist with large affinity for 5-HT(2A/2C) serotonergic receptors, which, in this case, caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT(2A/2C) receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures.
发作后不动综合征之后，动物和人类的伤害性感受阈值会显著升高。本研究的目的是评估中缝背核（DRN）在发作后抗伤害感受中的作用。第二个目的是研究DRN的5-羟色胺能内在机制在这种痛觉减退现象中的作用。戊四氮（PTZ）是一种离子载体GABA介导的Cl(-)内流拮抗剂，经外周给药用于诱导Wistar大鼠的强直阵挛性发作。通过甩尾试验测量伤害性感受阈值。用微量注射鹅膏蕈氨酸（1.0微克/0.2微升）对DRN进行神经化学损伤，导致强直阵挛性发作诱导的抗伤害感受显著降低，表明该核参与了这一抗伤害感受过程。向DRN微量注射麦角新碱（1.0和5.0微克/0.2微升），一种非选择性5-羟色胺能受体拮抗剂，与对照组相比，在目前研究的所有发作后时期，均导致发作动物的发作后抗伤害感受显著降低。向DRN微量注射酮色林（1.0和5.0微克/0.2微升）证实了这些发现。酮色林是一种对5-HT(2A/2C)5-羟色胺能受体具有高亲和力的拮抗剂，在这种情况下，与强直阵挛性惊厥反应后的前20分钟后的对照组相比，导致发作动物的甩尾潜伏期显著缩短。这些结果表明，DRN神经元簇的5-羟色胺能神经传递参与了发作后痛觉减退的机制。DRN神经元的5-HT(2A/2C)受体似乎在强直阵挛性发作后伤害性感受阈值的升高过程中起关键作用。
