木丹颗粒治疗糖尿病性周围神经病变的作用机制

文中对木丹颗粒在组方原则、作用机制、疗效特点等方面进行了分析。该药物是通过调整影响神经代谢物质水平、修复受损神经、提高神经传导速度、解除机体疼痛症状、改善血液微循环等综合作用,延缓或逆转糖尿病周围神经病变（DPN）的发生和发展。同时笔者概述了木丹颗粒的研发背景及组方原则,列举了现用于DPN的辅助治疗药物,提出木丹颗粒为专门用于治疗DPN的新药,木丹颗粒早期介入治疗可延缓或阻止DPN的发生。     

盐酸丁咯地尔治疗糖尿病周围神经病变 40例分析

目的 观察盐酸丁咯地尔注射液治疗糖尿病周围神经病变( ) DPN 的疗效。方法 将 80例 DPN 患者随机分成 2组,各 40例,对照组采用 DPN 的常规治疗方法,治疗组在对照组用药基础上加用盐酸丁咯地尔注射液治疗,每日静滴 150m g,用药 4周。结果 治疗 4周后,盐酸丁咯地尔治疗组对改善 DPN 患者的肢体疼痛、麻木、感觉异常等临床症状的总有效率为 79.2%,较对照组 53.3%有非常显著性差异(P <0.01) ,对神经传导速度的改善率 65.0%,较对照组 40.0%有非常显著性差异 (P <0.01) 。无明显不良反应。结论 盐酸丁咯地尔注射液对改善 DPN 患者的临床症状有明显疗效,且可以改善神经传导速度, 是有效的 DPN 治疗药物。     

银杏达莫联合甲钴胺治疗糖尿病周围神经病变的临床观察

糖尿病周围神经病变(DPN)作为糖尿病常见的慢性并发症,发病率高,临床症状以持续性疼痛、麻木及感觉减退为主要表现,给患者带来极大痛苦,但在目前尚缺乏疗效显著的治疗手段。由于DPN发病机制复杂,有多种病理因素参加,存在多个作用环节,因而仅针对某个病理作用环节的单独用药取得的临床疗效还不能令人十分满意。为提高疗效有必要探究作用于多个病理环节的最佳联合用药方案。为此,本文试用中药血管活性药物银杏达莫联合神经修复剂甲钴胺对DPN患者进行临床治疗研究。为评价联合治疗方案的临床疗效与安全性,本研究应用前瞻性、随机开放式临床…     

糖尿病周围神经病变治疗药物研究进展

目的:为糖尿病周围神经病变(DPN)的药物治疗提供参考。方法:就近年来DPN药物治疗研究进展进行文献归纳和综述。结果:用于对因治疗的西药包括控制血糖的药物(如胰岛素、磺酰脲类药物等)、扩张血管及改善微循环的药物(如钙离子拮抗药、血管紧张素Ⅱ-1型受体拮抗药、血管紧张素转换酶抑制剂等)、降低血黏度及抗凝和溶栓药物(如前列腺素E1及其类似物、阿司匹林等)、改善代谢紊乱的药物(如肌醇、醛糖还原酶抑制剂等)、抗氧化的药物(如α-硫辛酸、维生素E和维生素C等)、增加神经营养与修复神经的药物(如甲钴胺、神经生长因子等),用于对症治疗的西药主要是减轻或缓解疼痛的药物(如非甾体抗炎药、三环类抗抑郁药、抗惊厥药等),中医药治疗DPN的方法包括内服中药(如活血化瘀类中药)、使用中药注射剂(如丹参注射液、丹红注射液等)、针灸刺络、熏洗足浴。结论:DPN的发病机制复杂,其治疗除严格控制血糖外,还要从其他途径入手,针对导致DPN的各种病因探索更有效、更特异性的治疗方案,寻找治疗的新靶点将是今后研发DPN治疗药物的方向。     

痛性糖尿病神经病变的药物止痛治疗

痛性糖尿病神经病变是临床上慢性疼痛综合征最常见的原因之一,疼痛机制目前尚未完全阐明,比较认同的学说为中枢和(或)周围神经损伤,继而发生神经修复,引起疼痛。相应的治疗多为经验性与综合性用药,药物治疗在针对疼痛的同时,还要考虑改善神经功能。     

注射用鼠神经生长因子治疗糖尿病周围神经病变的临床分析

<正>糖尿病周围神经病变(diabetic peripheral neurology,DPN)是糖尿病常见的慢性并发症,临床多表现为肢体疼痛、麻木及感觉减退等,临床中的治疗除积极控制血糖外,还应用神经营养素等,如维生素B12,但疗效并不显著,在本研究中使用注射用鼠神经生长因子作为治疗DPN的药物,并与维生素B12相比较两者疗效以期取得新的治疗方案。     

缬沙坦联合甲钴胺注射液治疗糖尿病周围神经病变临床研究

糖尿病周围神经病变(DPN)是糖尿病常见的慢性并发症之一,临床以疼痛、麻木及感觉减退为主要表现,目前尚缺乏有效的治疗手段.我科应用血管紧张素受体拮抗剂缬沙坦联合神经修复剂甲钴胺注射液对DPN患者进行临床治疗研究.现报告如下.     

针灸并用丹红注射液治疗糖尿病周围神经病变疗效观察

目的观察针灸合用药物治疗糖尿病周围神经病变(DPN)的临床疗效。方法采用随机法将94例2型糖尿病患者分为治疗组和对照组。治疗组在对照组的用药的基础上予以固本通络为治疗原则的电针疗法联合静滴丹红注射液;对照组予以西药维生素B1,甲钴胺片口服,疗程2个星期。观察患者临床疗效及神经传导速度等变化情况。结果治疗组临床疗效及神经传导功能明显优于对照组(P<0.05),差异有统计学意义。结论针药并用可以改善DPN患者的临床症状和体征,优于单用西药治疗,是治疗DPN的一种有效方法。     

糖尿病痛性神经病治疗的现状和未来

糖尿病痛性神经病（DPN）是最常见的神经疾病。证据显示阿片类药物、抗癫痫药、抗抑郁药和辣椒素都能有效缓解DPN。曲马多和羟考酮在用药期内对DPN是有效的,但它们的副作用,如便秘和躯体依赖,限制了其作为一线药使用。加巴喷丁类药物,如加巴喷丁和普瑞巴林,是抗癫痫药中有效证据最多的DPN治疗药。较新的药物中lacosamide似乎最有希望。辣椒素是最好的局部药剂,局麻贴片也是一种有益治疗。目前还不能指定一种单药用于DPN的一线治疗,两种药物低剂量组合,缓解症状较好,副作用也较少,但需进一步研究以确定最佳组合。     

中西医结合治疗糖尿病周围神经病变的临床疗效观察

目的观察中西医结合的方法对糖尿病周围神经病变(DPN)疗效。方法采用川芎嗪+尼莫地平对DPN患者进行治疗。结果此方法能明显改善临床症状,提高神经传导速度。结论川芎嗪+尼莫地平是治疗DPN的理想药物,在临床上有推广应用的价值。     

Antiepileptic drugs in the treatment of neuropathic pain

Antiepileptic drugs are an effective treatment for various forms of neuropathic pain of peripheral origin, although they rarely provide complete pain relief. Multiple multicentre randomised controlled trials have shown clear efficacy of gabapentin and pregabalin for postherpetic neuralgia and painful diabetic neuropathy. Theses drugs can be rapidly titrated and are well tolerated. Topiramate, lamotrigine, carbamazepine and oxcarbazepine are alternatives for the treatment of painful diabetic neuropathy, but should be titrated slowly. Carbamazepine remains the drug of choice for trigeminal neuralgia; however, oxcarbazepine and lamotrigine are potential alternatives.There is an apparent need for large-scale randomised controlled trials on the efficacy of antiepileptic drugs in neuropathic pain in general, and in cancer-related neuropathic pain and neuropathic pain of central origin in particular. Trials with long-term follow-up are required to establish the long-term efficacy of antiepileptic drugs in neuropathic pain. There is only limited scientific evidence to support the idea that drug combinations are likely to be more efficacious and safer than each drug alone; further studies are warranted in this area.     

Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain

Neuropathic pain includes postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A) has been known for its analgesic effect in various pain conditions. Nevertheless, there are no data of nerve block in PHN and PDN. Here, we report two patients successfully treated with ultrasound-guided peripheral nerve block using BoNT-A for intractable PHN and PDN. One patient had PHN on the left upper extremity and the other patient had PDN on a lower extremity. Due to side effects of drugs, escalation of the drug dose could not be made. We injected 50 Botox units (BOTOX^®, Allergan Inc., Irvine, CA, USA) into brachial plexus and lumbar plexus, respectively, under ultrasound. Their pain was significantly decreased for about 4–5 months. Ultrasound-guided nerve block with BoNT-A may be an effective analgesic modality in a chronic intractable neuropathic pain especially when conventional treatment failed to achieve adequate pain relief.     

Role of topiramate for the treatment of painful diabetic peripheral neuropathy

OBJECTIVE: To review the possible role of topiramate for the treatment of neuropathic pain and, specifically, the pain of diabetic peripheral neuropathy. DATA SOURCES: Clinical studies and abstracts were identified by using PubMed (January 1966--October 2003), Ovid (January 1966--December 2003), and International Pharmaceutical Abstracts (January 1970--December 2003) and by reviewing bibliographies of published studies. Key search terms included pain, peripheral neuropathy, diabetes, and topiramate. English-language studies were identified, as were pertinent references from these articles. DATA SYNTHESIS: Published data are limited on the successful use of topiramate in the treatment of neuropathic pain syndromes, and only three prospective studies evaluated the effectiveness of topiramate in diabetic peripheral neuropathy. In addition, the use of topiramate to treat diabetic neuropathic pain syndromes successfully may be limited by patients' inability to tolerate the adverse effects associated with the agent. CONCLUSIONS: Topiramate has been used successfully in relieving the pain of various neuropathies, including painful diabetic peripheral neuropathy. Randomized controlled trials that specifically focus on the use of topiramate in patients with painful diabetic peripheral neuropathy are needed to confirm the initial findings in case reports, abstracts, and small clinical trials that have focused on treating numerous neuropathic pain syndromes, including diabetic peripheral neuropathy.     

Discovery of 4-aminobutyric acid derivatives possessing anticonvulsant and antinociceptive activities: a hybrid pharmacophore approach

Antiepileptic drugs are often utilized in the treatment of neuropathic pain. The present study aims at the design and synthesis of newer gamma-aminobutyric acid (GABA) derivatives with the combination of aryl semicarbazone and the GABA pharmacophores in order to develop a multifunctional drug useful in the treatment of neurological disorders like epilepsy and neuropathic pain. Various GABA semicarbazones were synthesized and screened for anticonvulsant, peripheral analgesic, antiallodynic, and antihyperalgesic activities. The structures of the synthesized compounds were confirmed by the use of their spectral data in addition to elemental analysis. The synthesized derivatives of the inhibitory neurotransmitter GABA produced anticonvulsant and antinociceptive actions in the acetic acid induced writhing test and peripheral nerve injury (chronic constriction injury and L5 spinal nerve ligation) models of neuropathic pain. The underlying mechanisms are expected to be enhancement of peripheral GABAergic neurotransmission owing to their activity in the scPIC screen and due to various reports on the involvement of GABAergic pathway in peripheral models of neuropathic pain.     

Cytokine Modulation is Necessary for Efficacious Treatment of Experimental Neuropathic Pain

Neuropathic pain originates from a damage or disease affecting the somatosensory system. Its treatment is unsatisfactory as it appears refractory to most analgesics. Animal models of neuropathic pain are now available that help to clarify the underlying mechanisms. Recently it has been recognized that inflammatory and immune mechanisms in the peripheral and in the central nervous system play a role in the onset and the maintenance of pain. In response to nervous tissue damage, activation of resident or recruited immune cells leads to the production of inflammatory mediators, as cytokines. In models of neuropathic pain, such as nerve injury and diabetes induced neuropathy, the time course of the expression of the proinflammatory cytokines TNF-α,IL-1β and IL-6 and of the antiinflammatory cytokine IL-10 has been well characterized both in the peripheral (sciatic nerve, dorsal root ganglia) and the central (spinal cord) nervous system. These cytokines appear activated/modulated in the nervous tissue in parallel with the occurrence of painful behaviour, i.e. allodynia and hyperalgesia. Novel therapeutic approaches efficacious to reduce painful symptoms, for example treatments with the non specific purinergic antagonist PPADS, the phytoestrogen genistein and a cell stem therapy with murine adult neural stem cells also re-established a balance between pro and antinflammatory mediators in the peripheral and central nervous system. These data suggest a pivotal role of immune system and inflammation in neuropathic pain. The modulation of inflammatory molecules appears to be a common trait accomplished throughout different mechanisms by different drugs that might converge in neuropathic pain modulation.     

Mechanisms and pharmacology of diabetic neuropathy – experimental and clinical studies

Neuropathic pain is the most common chronic complication of diabetes mellitus. The mechanisms involved in the development of diabetic neuropathy include changes in the blood vessels that supply the peripheral nerves; metabolic disorders, such as the enhanced activation of the polyol pathway; myo-inositol depletion; and increased non-enzymatic glycation. Currently, much attention is focused on the changes in the interactions between the nervous system and the immune system that occur in parallel with glial cell activation; these interactions may also be responsible for the development of neuropathic pain accompanying diabetes. Animal models of diabetic peripheral neuropathy have been utilized to better understand the phenomenon of neuropathic pain in individuals with diabetes and to define therapeutic goals. The studies on the effects of antidepressants on diabetic neuropathic pain in streptozotocin (STZ)-induced type 1 diabetes have been conducted. In experimental models of diabetic neuropathy, the most effective antidepressants are tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors. Clinical studies of diabetic neuropathy indicate that the first line treatment should be tricyclic antidepressants, which are followed by anticonvulsants and then opioids. In this review, we will discuss the mechanisms of the development of diabetic neuropathy and the most common drugs used in experimental and clinical studies.     

Targeting N-methyl-D-aspartate receptors for treatment of neuropathic pain

Neuropathic pain remains a major clinical problem and a therapeutic challenge because existing analgesics are often ineffective and can cause serious side effects. Increased N-methyl-d-aspartate receptor (NMDAR) activity contributes to central sensitization in certain types of neuropathic pain. NMDAR antagonists can reduce hyperalgesia and allodynia in animal models of neuropathic pain induced by nerve injury and diabetic neuropathy. Clinically used NMDAR antagonists, such as ketamine and dextromethorphan, are generally effective in patients with neuropathic pain, such as complex regional pain syndrome and painful diabetic neuropathy. However, patients with postherpetic neuralgia respond poorly to NMDAR antagonists. Recent studies on identifying NMDAR-interacting proteins and molecular mechanisms of increased NMDAR activity in neuropathic pain could facilitate the development of new drugs to attenuate abnormal NMDAR activity with minimal impairment of the physiological function of NMDARs. Combining NMDAR antagonists with other analgesics could also lead to better management of neuropathic pain without causing serious side effects.     

Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy

Neuropathic pain, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human models of neuropathic pain has shown that a number of pathophysiological and biochemical changes take place in the nervous system as a result of an insult. This property of the nervous system to adapt morphologically and functionally to external stimuli is known as neuroplasticity and plays a crucial role in the onset and maintenance of pain symptoms. Many similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders. Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic neuralgia. The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapentin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain. Evidence for the efficacy of phenytoin as an antinociceptive agent is, at best, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although another randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have antihyperalgesic and antinociceptive activities based on result in animal models of neuropathic pain, but the efficacy of these drugs in the treatment of human neuropathic pain has not yet been fully determined in clinical trials. The role of anticonvulsant drugs in the treatment of neuropathic pain is evolving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropathic pain syndromes and well-designed clinical trials should further the opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.     

Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats

This study was conducted to examine the role of nitric oxide (NO) in peripheral neuropathy induced by chronic constriction injury of sciatic nerve of rats by using NO precursor, NO donors and nitric oxide synthase (NOS) inhibitors. Chronic constriction injury of sciatic nerve of rats resulted in peripheral neuropathy as confirmed by nociceptive behavioural tests using mechanical, thermal and cold allodynia. NO precursor, L-arginine and NO donors sodium nitroprusside, S-nitroso-N-acetylpenicillamine potentiated the hyperalgesia and allodynia significantly suggesting proalgesic effect in neuropathic rats. Intracerebroventricular (i.c.v.) administration of rats with NOS inhibitors such as L-N(G)-nitroarginine methyl ester, N-iminoethyl lysine and 7-nitroindazole did not show any effect but i.p. administration of NOS inhibitors aminoguanidine, L-N(G)-nitroarginine methyl ester and 7-nitroindazole caused alleviation of pain. The study confirms the involvement of endogenously synthesized and exogenously administered NO in chronic constriction injury-induced neuropathy in rats. Significant increase in the levels of nitrate and nitrite in ligated sciatic nerve suggest that local up regulation of NO in the production and maintenance of neuropathic pain. In conclusion, initial attempt to manipulate L-arginine: NO pathway is indicative of therapeutic potential of these interventions in the management of neuropathic pain.