大鼠丘脑中央下核内注射5-HT2受体拮抗剂噻庚啶对强电针镇痛的阻断效应

以辐射热诱发浅麻大鼠甩尾(TF)反射潜伏期为痛反应指标,观察了不同强度电针的镇痛效应及丘脑中央下核(Sm)内微量注射5-HT2受体拮抗剂噻庚啶(CPT)对其效应的影响.结果表明,弱电针刺激(0.5mA)"足三里穴”仅可轻度抑制大鼠TF反射,而强电针(5 mA)对TF反射的抑制作用明显大于弱电针;单侧Sm内微量注射CPT(50 ng)可轻度易化TF反射,并使强电针的镇痛效应明显减弱,而对弱电针的效应无明显影响.提示Sm内的5-HT及其受体亚型(5-HT2受体)可能参与强电针的镇痛效应并具有紧张性下行抑制性影响.     

丘脑中央下核和顶盖前区前核分别参与介导强电针和弱电针的镇痛效应

在大鼠以强电刺激外周感受野诱发的脊髓背角ＷＤＲ和ＮＳ神经元的晚串放电（Ｃ－反应）作为伤害感受性反应,观察了双侧丘脑中央下核（Ｓｍ）或顶盖前区前核（ＡＰｔＮ）内微量注射局麻药利多卡因对不同强度电针引起的镇痛效应的影响。结果表明：双侧Ｓｍ局麻可明显减弱强电针对Ｃ－反应的抑制效应,但对弱电针的抑制效应无明显影响;双侧ＡＰｔＮ局麻可明显减弱弱电针对Ｃ－反应的抑制效应,但对强电针的抑制效应无明显影响。结果提示,不同强度的电针刺激可能由粗细不同的纤维传入,通过不同的中枢机制产生镇痛作用。Ｓｍ参与介导强电针兴奋细纤维产生的镇痛作用;ＡＰｔＮ则参与介导弱电针兴奋粗纤维产生的镇痛作用。     

丘脑中央下核和顶盖前区前核分别参与介导强电针和弱电针的 …

在大鼠以强电刺激外周感受野诱发的脊髓背角ＷＤＲ和ＮＳ神经元的晚串放电（Ｃ－反应）作为伤害感受性反应，观察了双侧丘脑中央下核（Ｓｍ）或顶盖前区前核（ＡＰｔＮ）内微量注射局麻药利多卡因对不同强度电针引起的镇痛效应的影响。结果表明：双侧Ｓｍ局麻可明显减弱强电针对Ｃ－反应的抑制效应，但对弱电针的抑制效应无明显影响，双侧ＡＰｔＮ局麻可明显减弱弱电针对Ｃ－反应的抑制效应，但以强电针的抑制效应无明显影响，结果提     

抑制大鼠大脑皮层SI区对电针抑制持续性痛反应的影响

在大鼠用玻璃微电极细胞外记录的方法,观察了电针同侧前肢“合谷”、“内关”穴对皮下注射福尔马林（５％ ,５０ μｌ）诱发的脊髓背角广动力型（ＷＤＲ）神经元晚时相放电反应的影响。结果表明,低频强电针（５ Ｈｚ, ５～６ ｍ Ａ）和高频弱电针（５０ Ｈｚ, １ ｍ Ａ）都可对背角ＷＤＲ神经元的晚时相反应产生明显的抑制作用,且低频强电针的抑制作用大于高频弱电针的作用。用４％ ＭｇＳＯ４ 抑制皮层体感Ⅰ区（ＳＩ区）的活动后,低频强电针对ＷＤＲ神经元晚时相反应的抑制作用明显减弱,提示ＳＩ区在电针对持续性痛的镇痛机制中具有重要作用。     

蓝斑参与刺激下丘脑视上核引起的加强电针镇痛

本工作应用核团灌流液的放射免疫测定（ＲＩＡ），高压液相（ＨＰＬＣ）以及核团内注射拮抗剂，观察了蓝斑（ＬＣ）在刺激下丘脑视上核（ＳＯＮ０引起的加强电针（ＥＡ）镇痛效应中的作用，结果表明，化学检测ＳＯＮ后电针期间和停针后３０，６０ｍｉｎ蓝斑灌流液内ＯＴ的含量明显升高，刺激ＳＯＮ后电针期间灌流液内精氨酸加压素（ＡＶＰ）含量明显升高，停针后ＡＶＰ的含量虽高于对照组及注射前的水平，但无统计学意义，ＬＣ灌流夜     

中脑导水管周围灰质内神经降压素可增强β-内啡肽的镇痛效应

目的探讨大鼠中脑导水管周围灰质内神经降压素对β-内啡肽在痛行为反应中的影响。方法以钾离子透入法引起大鼠甩尾反应的电流强度（mA）作为痛行为反应的指标,观察大鼠中脑导水管周围灰质内注入β-内啡肽、抗β-内啡肽血清、神经降压素和抗神经降压素血清对大鼠痛阈的影响。结果中脑导水管周围灰质内注入β-内啡肽后,大鼠痛阈明显升高;注入抗β-内啡肽血清后,痛阈则明显降低。中脑导水管周围灰质内注入微量神经降压素后,可明显加强β-内啡肽的镇痛效应;注入抗神经降压素血清后,则明显削弱β-内啡肽的镇痛效应。结论神经降压素参与中脑导水管周围灰质内注射β-内啡肽引起的镇痛效应。     

抵制大鼠大脑皮层SI区对电针抵制持续性痛反应的影响

在大鼠用玻璃微电极细胞外记录的方法，观察了电针同侧前肢“合谷”、“内关”穴对皮下注射福尔马林（５％，５０μ１）诱发的脊髓背角广动力型（ＷＤＲ）神经元晚时相放电反应的影响。结果表明，低频强电什（５ＨＺ，５￣６ｍＡ）和高频弱电针（５０ＨＺ，１ｍＡ）都可对背角ＷＤＲ神经元的晚时相反应产生明显的抑制作用，且低频强电针的抑制作用大于高频弱电针的作用。用４％ＭｇＳＯ４抑制皮层体感Ⅰ区（ＳＩ区）的活动后，低频强     

中枢P物质参与电针镇痛的证据

本文采用放射免疫分析和甩尾测试法观察不同频率电针对大鼠脊髓Ｐ物质（ＳＰ）释放的影响。发现在电针有效组，２Ｈｚ（低频）电针时大鼠脊髓灌流液中ＳＰ—ｉｒ明显减少，而１５Ｈｚ（中频）、１００Ｈｚ（高频）和２／１５Ｈｚ（变频）刺激时，ＳＰ—ｉｒ明显增加。在电针无效组，各种频率电针时的ＳＰ—ｉｒ测定均无明显变化。脊髓蛛网膜下腔（ｉ．ｔ．）注射高选择性非肽类ＳＰ受体拮抗剂ＲＰ６７５８０可明显阻断１５Ｈｚ、１００Ｈｚ和２／１５Ｈｚ电针镇痛，而对ＺＨＺ电针镇痛无影响。注射ＲＰ６７５８０的同分异构体ＲＰ６８６５１则不能阻断上述各频率的电针镇痛作用。鉴于中、高频和变频电针促进脊髓ＳＰ的释放，而阻断ＳＰ受体可阻断上述电针镇痛，提示电针引起大鼠脊髓中释放的ＳＰ不是参与伤害感受，而是发挥了镇痛作用．关键词     

苍白球在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨苍白球在电针镇痛及兴奋尾壳核镇痛中的作用。结果表明 :电针可以延长辐射热引起的缩腿潜伏期 ,电针或兴奋尾壳核可抑制丘脑束旁核神经元的伤害性反应 ;苍白球微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响 ,与毁损前相比有显著性差异 (P <0 .0 5 ) ,与苍白球微量注射生理盐水 7d后 ,电针可延长大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比有显著性差异 (P <0 .0 5 )。结果提示 :苍白球在电针及兴奋尾壳核镇痛中发挥重要作用     

中枢神经系统一氧化氮对大鼠的痛觉调制作用

以钾离子透入引起大鼠甩尾的电流强度(mA)作为痛反应指标,采用侧脑室微量注射L-精氨酸(L-Arg)、亚甲基蓝(MB)等,观察大鼠痛阈的变化,分析探讨中枢神经系统中一氧化氮(NO)对大鼠痛觉的调制作用.结果显示:大鼠侧脑室微量注射NO前体及供体物质L-Arg和硝普钠(SNP)均引起明显的痛敏效应.微量注射MB和L-NAME后大鼠痛阈升高非常显著.侧脑室微量注射MB和L-Arg混合液后,大鼠痛阈较单纯注射MB组表现出明显降低的趋势,但与L-Arg组相比大鼠痛阈升高明显.提示:提高中枢内NO水平具有明显的痛敏效应,而降低中枢神经系统NO水平表现显著镇痛作用.中枢神经系统NO对大鼠痛觉的调制作用至少部分是通过NO-cGMP途径实现的.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.