Therapeutic potential of cannabinoids in CNS disease

The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.     

CT 引导下射频复合阿霉素介入治疗三叉神经痛的临床观察

目的：研究CT引导下阿霉素复合热凝射频对三叉神经痛的临床疗效及安全性。方法三叉神经痛患者60例,随机分为A组和B组,每组30例。在CT引导下,所有患者行半月神经节穿刺,A组患者给予阿霉素治疗,B组给予热凝射频＋阿霉素治疗。比较2组患者起效时间,治疗前、治疗后1周、1个月、2个月、4个月和8个月的疗效评分、视觉模拟评分（ VAS）和睡眠评分,同时观察患者术后不良反应。结果 B组起效时间明显短于A组（ P ＜0．05）,治疗后1周、2个月、4个月和8个月的优良率明显高于A组（ P ＜0．05）。 B组治疗后1周、2个月、4个月和8个月VAS评分明显低于A组,治疗后2个月、4个月和8个月的睡眠评分明显高于A组（ P ＜0．05）。 B组麻木发生率高于A组（ P ＜0．05）,其他不良反应相比差异无统计学意义（ P ＞0．05）。结论 CT引导下热凝射频复合阿霉素治疗三叉神经具有起效快,疗效长的优点,值得临床推广。     

Dofetilide induced trigeminal neuralgia

Anti-arrhythmic medications are uncommonly used due to their pro-arrhythmic effect. However, just like any other class of medication, they can cause idiosyncratic reactions that may or may not be related to their mechanism of action. Those reactions can be severe enough to warrant discontinuation of a successful therapeutic intervention. In this case, we present a case of trigeminal neuralgia caused by dofetilide.KEY WORDS: Adverse effects, dofetilide, trigeminal neuralgia     

Therapeutic potential of cannabinoids in the treatment of neuroinflammation associated with Parkinson's disease

The cannabinoid system is represented by two principal receptor subtypes, termed CB1 and CB2, along with several endogenous ligands. In the central nervous system it is involved in several processes. CB1 receptors are mainly expressed by neurons and their activation is primarily implicated in psychotropic and motor effects of cannabinoids. CB2 receptors are expressed by glial cells and are thought to participate in regulation of neuroimmune reactions. This review aims to highlight several reported properties of cannabinoids that could be used to inhibit the adverse neuroinflammatory processes contributing to Parkinson's disease and possibly other neurodegenerative disorders. These include anti-oxidant properties of phytocannabinoids and synthetic cannabinoids as well as hypothermic and antipyretic effects. However, cannabinoids may also trigger signaling cascades leading to impaired mitochondrial enzyme activity, reduced mitochondrial biogenesis, and increased oxidative stress, all of which could contribute to neurotoxicity. Therefore, further pharmacological studies are needed to allow rational design of new cannabinoid-based drugs lacking detrimental in vivo effects.     

原发性三叉神经痛的显微手术治疗

目的 探讨原发性三叉神经痛病因及显微血管减压治疗.方法 回顾性分析显微血管减压术治疗的60例原发性三叉神经痛病例资料.结果 术后疼痛完全缓解58例(96.7%),明显缓解、对症处理能够控制满意者2例.出现术侧耳鸣2例,面瘫2例,脑脊液漏1例.随访3～48个月,无复发病例.结论 三叉神经入脑干区受血管压迫是原发性三叉神经痛的常见病因.显微血管减压术是有效的治疗方法.充分认识责任血管,术中注重手术技巧,是提高手术安全性和减少并发症的关键措施.     

三叉神经痛大鼠三叉神经节中BDNF的表达变化

目的观察脑源性神经生长因子(brain-derived neurotropic factor,BDNF)及其高亲和力受体TrkB在三叉神经痛(trigeminal neuralgia,TN)大鼠三叉神经节(trigeminal ganglion, TG)中的表达变化。方法 TN大鼠模型由眶下神经慢性损伤压迫模型(ION-CCI)制备。♂SD大鼠随机分为假手术组(Sham组)和TN模型组。测定两组大鼠损伤侧机械阈值,应用实时荧光定量PCR、免疫组织化学技术和免疫荧光双标技术,检测损伤侧TG中BDNF及TrkB表达变化,并测定损伤侧TG中前炎症因子TNF-α、IL-1β的变化。结果建模2周后,与假手术组相比,TN组的机械痛阈明显下调,TG中BDNF及TrkB较假手术组明显升高,同时前炎症因子TNF-α、IL-1β水平也明显升高(P<0.05)。结论 TN状态下,ION-CCI大鼠TG中BDNF及TrkB表达升高,可能参与TN的发病机制,促进了TN的痛觉传递。     

三叉神经痛的分子发病机制的研究进展

三叉神经痛(trigeminal neuralgia,TN)是指三叉神经的一支或几支分布区的反复性、阵发性剧痛,对病人的生活质量影响较大的一种较难完全治愈的疾病,临床一般分为原发性和继发性TN。关于原发性TN的病因和发病机制目前尚不明确。现在,随着分子生物学研究的进展,已经发现多种神经类物质和TN有着密切的联系。该文从分子方面对TN的发病机制研究进展情况作一综述,旨在为TN的治疗提供理论依据。     

消退素D1抗三叉神经痛的研究

目的 探讨消退素D1的抗三叉神经痛作用。方法 健康SD大鼠按体质量随机分为模型组、消退素D1（30、90、270 μg/kg）组和苯妥英钠阳性对照组,采用脑内注射青霉素G钾致大鼠三叉神经痛模型,考察消退素D1抗三叉神经痛作用。健康SD大鼠按体质量随机分为假手术组、模型组、消退素D1（30、90、270 μg/kg）组和苯妥英钠阳性对照组,采用慢性压迫性损伤眶下神经致大鼠三叉神经痛模型,考察消退素D1抗三叉神经痛作用。结果 消退素D1（30、90、270 μg/kg）能够显著延长大鼠出现疼痛反应（发生尖叫、甩头和后肢抓挠面部）的潜伏期,减少大鼠60 min内的疼痛反应时间;能够显著升高慢性压迫性损伤大鼠眶下神经致三叉神经痛模型大鼠的疼痛反应阈值。结论 消退素D1具有抗三叉神经痛作用。     

克林霉素磷酸酯致耳鸣和三叉神经痛

1例40岁肺部感染男性患者，给予克林霉素磷酸酯600mg静脉滴注治疗后出现轻度耳鸣。6h后第2次滴注，又出现耳呜，伴恶心呕吐，之后耳鸣加重和左侧面部电击样痛。疼痛发作共10余次，每次持续数秒至2min，诊为三叉神经痛。停用克林霉素，12h后症状缓解。     

The therapeutic potential of the cannabinoids in neuroprotection

After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the legislature of modern medicine to these compounds. The ability of this diverse family of compounds to modulate neurotransmission and act as anti-inflammatory and antioxidative agents has prompted researchers to investigate their potential as neuroprotective agents. Indeed, various cannabinoids rescue dying neurones in experimental forms of acute neuronal injury, such as cerebral ischaemia and traumatic brain injury. Cannabinoids also provide symptomatic relief in experimental models of chronic neurodegenerative diseases, such as multiple sclerosis and Huntington's disease. This preclinical evidence has provided the impetus for the launch of a number of clinical trials in various conditions of neurodegeneration and neuronal injury using compounds derived from the cannabis plant. Our understanding of cannabinoid neurobiology, however, must improve if we are to effectively exploit this system and take advantage of the numerous characteristics that make this group of compounds potential neuroprotective agents.     

The therapeutic potential of the cannabinoids in neuroprotection

After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the legislature of modern medicine to these compounds. The ability of this diverse family of compounds to modulate neurotransmission and act as anti-inflammatory and antioxidative agents has prompted researchers to investigate their potential as neuroprotective agents. Indeed, various cannabinoids rescue dying neurons in experimental forms of acute neuronal injury, such as cerebral ischaemia and traumatic brain injury. Cannabinoids also provide symptomatic relief in experimental models of chronic neurodegenerative diseases, such as multiple sclerosis and Huntington’s disease. This preclinical evidence has provided the impetus for the launch of a number of clinical trials in various conditions of neurodegeneration and neuronal injury using compounds derived from the cannabis plant. Our understanding of cannabinoid neurobiology, however, must improve if we are to effectively exploit this system and take advantage of the numerous characteristics that make this group of compounds potential neuroprotective agents.     

Oxcarbazepine. A review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders.

Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct pharmacokinetic profile. In contrast to the oxidative metabolism of carbamazepine, oxcarbazepine is rapidly reduced to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. With the possible exception of the P450IIIA isozyme of the cytochrome P450 family, neither oxcarbazepine nor its monohydroxy derivative induce hepatic oxidative metabolism. Direct comparison of oxcarbazepine and carbamazepine has shown no difference in efficacy between these 2 agents in terms of reducing seizure frequency in patients with partial epilepsy with or without secondary generalisation, or with tonic-clonic seizures. Substitution of oxcarbazepine for carbamazepine in multiple antiepileptic drug regimens improved seizure control in some patients with refractory epilepsy; however, the rise in serum concentrations of concurrent antiepileptic agents secondary to elimination of carbamazepine-associated hepatic enzyme induction may have also played a role. Substitution of oxcarbazepine for carbamazepine was associated with improved cognition and alertness in some patients with epilepsy. Limited data indicate that oxcarbazepine may be a useful alternative to carbamazepine in the management of trigeminal neuralgia. Experience in patients with acute mania is promising, but the value of oxcarbazepine in managing affective disorders, particularly as a prophylactic agent, is not established. Oxcarbazepine may be better tolerated than carbamazepine; however, the current published database is small and the potential for oxcarbazepine to induce the type of serious idiosyncratic reactions occasionally associated with carbamazepine is unknown. Hyponatraemia has been reported in patients treated with oxcarbazepine. Although apparently asymptomatic, fluid restriction may be deemed necessary in some patients to reduce the risk of precipitating seizures secondary to low serum sodium. Thus, oxcarbazepine appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant drug interactions. Wider clinical experience should help clarify the long term efficacy and tolerability of oxcarbazepine. Pharmacokinetic advantages over current antiepileptic drugs, carbamazepine in particular, may then favour oxcarbazepine for consideration as a first-line agent in the management of partial and tonic-clonic epilepsy.     

微血管减压术治疗三叉神经痛的临床研究

目的探讨微血管减压术治疗三叉神经痛的手术效果、并发症和副作用,提出改良方案,提高对该病的诊疗效果。方法回顾性分析本院2008年8月～2011年4月收治住院的采用微血管减压手术治疗的原发性三叉神经痛患者74例,对手术技术及血管的处理方法进行改良,观察其治疗效果。结果手术的总有效率为98.6%,无一例发生脑脊液漏、听力丧失、颅内感染等严重并发症,术后随访发现复发率1.4%。结论微血管减压术从根本上解除了三叉神经痛的常见病因,术后完全保留了三叉神经各分支的功能,是目前手术治疗三叉神经痛的有效方法之一。     

射频治疗术治疗原发性三叉神经痛的护理

目的 总结原发性三叉神经痛患者射频手术治疗期间护理要点.方法 本院2014年3月至2015年3月收治的原发性三叉神经痛47例患者射频治疗术干预,为患者提供常规护理服务,作为一般组;2015年4月至2016年5月收治的47例患者提供优质护理干预,作为观察组;总结两组满意度、焦虑评分及干预前后机体疼痛度.结果 两组入院时中度及重度疼痛患者例数均较多,差异无统计学意义(均P＞0.05);经治疗及护理干预后,观察组无痛、轻度例数均高于一般组,中度及重度例数低于一般组,均P＜ 0.05.两组入院时焦虑评分差异无统计学意义(P＞0.05);经护理干预后,观察组评分低于一般组(P＜0.05).一般组满意度为70.21％,观察组为93.62％,P＜0.05.结论 对于原发性三叉神经痛的患者提供射频治疗术治疗,加强护理干预措施,大部分患者表示满意度较高,入院时患者因疼痛感均表现出较大程度的焦虑情绪,经干预后患者焦虑情绪得到良好改善,机体疼痛度有一定改善.     

显微手术治疗原发性三叉神经痛的临床体会

目的 探讨原发性三叉神经痛的病因及显微血管减压术的治疗效果.方法 回顾分析2010年1月至2014年12月收治的原发性三叉神经痛患者81例,行微血管减压术80例,同时行感觉根部分切断术22例,感觉根部分切断术加蛛网膜粘连松解1例,术中均严密缝合硬膜,术后随访半年以上,分析治疗效果.结果 81例患者中,术中发现有血管压迫80例,蛛网膜粘连1例,术后1天疼痛完全消失70例,术后1周疼痛完全消失8例,另外3例延迟缓解,术后无颅内感染及皮下积液等并发症,平均随访15个月.结论 显微手术行微血管减压术是治疗原发性三叉神经痛的最佳方法,根据情况可同时行感觉根部分切断术,疗效好,安全可靠,应作为原发性三叉神经痛患者的首选治疗方法.     

颅痛宁糖浆治疗特发性三叉神经痛的疗效观察

OBJECTIVETo observe the effect of Lu Tong-Ning syrupus In treatment of idiopathic trigeminal neuragia.METHODNine hundred and eighty- three patients with idiopathic trigeminal neuragina were radomLy divided into two groups.The Lu Tong-Ning group of 500 p