Neuman R S
Electroencephalogr Clin Neurophysiol. 1986 Dec;64(6):546-55. doi: 10.1016/0013-4694(86)90193-8.
Noxious stimulation has a well known suppressant effect on epileptiform activity in both laboratory animals and man. To study this phenomenon in an animal model, focal epileptiform activity was induced in anaesthetized rats by applying penicillin from one barrel of a micropipette while recording intracortical electrical activity from another barrel. Penicillin produced either focal epileptiform activity or focal penicillin spikes, depending somewhat on the rate of penicillin release. Focal epileptiform activity was suppressed by noxious stimulation, both somatic and olfactory, whereas non-noxious stimulation was ineffective in this regard. Focal penicillin spikes were only rarely suppressed by noxious stimulation. Reserpine blocked the suppressant effect of noxious stimulation as did p-chlorophenylalanine, a more selective depletor of 5-hydroxytryptamine. L-5-Hydroxytryptophan, a 5-hydroxytryptamine precursor, restored the suppressant effect of noxious stimulation blocked by reserpine and p-chlorophenylalanine. These results suggest that the suppression of SW by noxious stimulation is mediated by 5-hydroxytryptamine. Data from experiments employing pharmacological antagonists suggest the suppression of spike and wave activity by noxious stimulation not to be mediated by activation of dopamine receptors, alpha 2 or beta adrenoceptors, or muscarinic cholinoceptors. Prazosin, a selective alpha 1 adrenoceptor antagonist, did block the suppressant effect of noxious stimulation but only at a very high dose (2.4 mumols/kg). This likely reflects a known analgesic action of prazosin or weak binding to the 5-HT receptor. Methysergide, a 5-hydroxytryptamine antagonist, failed to antagonize the suppressant effect of noxious stimulation, however, many inhibitory actions of 5-hydroxytryptamine are not blocked by methysergide. It is concluded that suppression of focal epileptiform activity by noxious stimulation is mediated, at least in part, by 5-hydroxytryptamine.
伤害性刺激对实验动物和人类的癫痫样活动具有众所周知的抑制作用。为了在动物模型中研究这一现象，在麻醉大鼠中，通过微量移液器的一个管腔施加青霉素来诱导局灶性癫痫样活动，同时从另一个管腔记录皮质内电活动。青霉素产生局灶性癫痫样活动或局灶性青霉素棘波，这在一定程度上取决于青霉素的释放速率。伤害性刺激（包括躯体刺激和嗅觉刺激）可抑制局灶性癫痫样活动，而非伤害性刺激在这方面无效。局灶性青霉素棘波很少被伤害性刺激抑制。利血平阻断了伤害性刺激的抑制作用，对氯苯丙氨酸（一种更具选择性的5-羟色胺耗竭剂）也有同样的作用。5-羟色胺前体L-5-羟色氨酸恢复了被利血平和对氯苯丙氨酸阻断的伤害性刺激的抑制作用。这些结果表明，伤害性刺激对棘慢波的抑制作用是由5-羟色胺介导的。使用药理学拮抗剂的实验数据表明，伤害性刺激对棘波和慢波活动的抑制作用不是由多巴胺受体、α2或β肾上腺素能受体或毒蕈碱胆碱能受体的激活介导的。选择性α1肾上腺素能受体拮抗剂哌唑嗪确实阻断了伤害性刺激的抑制作用，但仅在非常高的剂量（2.4 μmol/kg）下。这可能反映了哌唑嗪已知的镇痛作用或与5-羟色胺受体的弱结合。5-羟色胺拮抗剂麦角新碱未能拮抗伤害性刺激的抑制作用，然而，5-羟色胺的许多抑制作用并未被麦角新碱阻断。得出的结论是，伤害性刺激对局灶性癫痫样活动的抑制作用至少部分是由5-羟色胺介导的。
