A型肉毒毒素作用于神经胶质细胞缓解神经病理性疼痛机制的研究进展

神经病理性疼痛是一个重要的临床问题,常规药物治疗效果不佳。A型肉毒毒素可缓解多种疼痛,其镇痛作用被认为与神经胶质细胞相关。本文概要介绍A型肉毒毒素作用于神经胶质细胞缓解神经病理性疼痛机制的研究进展,进一步探究A型肉毒毒素在神经病理性疼痛治疗上的临床潜力。     

神经病理性疼痛治疗药物的研究进展

神经病理性疼痛治疗药物的研究是目前药物设计及研究领域的热点和难点之一。本文对目前临床应用及正在研究中的、作用机制不同的及疗效较好的治疗神经病理性疼痛的药物类型及其适应证等作了综述，并对当前的研究现状及趋势作一展望。     

神经病理性疼痛发生机制的研究进展

为了获得高效治疗神经病理性疼痛的方法,本研究对近几年国内外神经病理性疼痛机制与治疗方面的研究进行分析。大量动物模型实验研究证实,脊髓背角星形胶质细胞激活、C-纤维的敏化调节、嘌呤受体信号的激活以及TNF-α细胞因子释放等途径或机制共同作用导致神经病理性疼痛的发生。针对这些机制的研究可指导临床从不同途径阻断疼痛的发生及发展过程,从而治疗该类疼痛,并可为通过减少外周刺激、提高疼痛阈值、阻断疼痛感觉传导等相应手段治疗神经病理性疼痛提供重要理论依据。     

糖尿病周围神经病变药物治疗的原则与策略

糖尿病周围神经病变(DPN)属于神经病理性疼痛,治疗方法多样,其中药物治疗是最主要的方法。DPN治疗的原则是积极控制血糖和早期积极有效地进行神经修复。治疗DPN的药物包括治疗神经病理性疼痛的药物、神经修复药物、局部治疗药物、抗氧化剂及钙拮抗药等。单一用药难以达到很好的效果,往往需要联合用药。     

晚期癌症病人的护理

维持病人生命的希望和满足病人的要求是晚期癌症病人护理的基本原则。具体护理重点是: 1 缓解疼痛 癌症通过多种机制产生疼痛,如侵入周围组织后对局部神经产生疼痛刺激,压迫神经根或神经干引起疼痛,静脉阻塞或动脉闭塞引起疼痛。病理性骨折损伤骨膜引起疼痛。镇痛治疗总以作用较小的药物开始,如阿斯匹林、消炎痛等。当此类药物无效时,     

基于炎症信号通路的生物碱治疗神经病理性疼痛的研究进展

神经病理性疼痛是由神经系统原发性损害和功能障碍所激发或引起的疼痛,炎症作为神经病理性疼痛发展的重要病机之一,是生物体对组织损伤做出的一种正常生理反应。炎症介导的神经病理性疼痛发展机制与外周神经敏化、中枢神经敏化息息相关,包括神经炎症反应、氧化应激反应、离子通道改变、胶质细胞的活化。常见的中药成分马钱子碱、小檗碱、去氢紫堇鳞茎碱、川芎嗪、氧化苦参碱、青藤碱均可缓解神经病理性疼痛。生物碱可通过多条途径影响神经病理性疼痛,其发挥的抗炎作用影响着外周神经敏化和中枢神经敏化,是治疗神经病理性疼痛的重要机制之一。因此生物碱介导的炎症反应具有良好的抗神经元损伤作用,对神经病理性疼痛产生一定的治疗作用。总结了炎症参与神经病理性疼痛和生物碱抗炎镇痛的机制,拟从分子层面阐释生物碱发挥抗神经病理性疼痛的作用机制。     

SNRIs类药物在神经病理性疼痛中的临床应用进展

5-羟色胺(5-HT)和去甲肾上腺素(NE)再摄取抑制剂(SNRIs)类药物主要在疼痛传导下行抑制通路中发挥抑制疼痛作用。SNRIs类药物广泛应用于糖尿病周围神经病理性疼痛、化疗诱导的周围神经病理性痛、幻肢痛等方面，目前为神经病理性疼痛一线推荐药物。该文就SNRIs类药物对神经病理性疼痛的作用机制及SNRIs药物在神经病理性疼痛的具体临床应用及注意事项进行综述，旨在为SNRIs类药物在神经病理性疼痛方面的临床应用提供参考。     

加巴喷丁用于神经病理性疼痛治疗的研究进展

研究表明加巴喷丁(gabapentin)可作用于脊髓背角神经原突触后钙离子通道，从而可能阻断了神经病理性疼痛产生的过程。临床证实加巴喷丁对糖尿病神经病变和带状疱疹后神经痛的治疗效果，是治疗神经病理性疼痛有效的药物。     

调控环磷腺苷信号通路治疗病理性疼痛

病理性疼痛是困扰人类健康的一种常见疾患,寻找合适的治疗靶点控制病理性疼痛是目前疼痛研究的一个重要方向。近年的研究发现,活化的炎细胞、神经胶质细胞在病理性疼痛中发挥重要作用。环磷腺苷是存在于多种细胞内的第二信使,有文献报道促进环磷腺苷通路能抑制炎细胞及胶质细胞活性,进而治疗病理性疼痛。该文对环磷腺苷通路抑制炎细胞及胶质细胞活化的机制,以及磷酸二酯酶抑制剂治疗病理性疼痛的研究现状做一综述。     

丝裂原活化的蛋白激酶:一个治疗病理性痛潜在的药物新靶点

病理性痛(pathological pain)是临床上常见的疼痛,通常分为炎性痛(inflammatory pain)和神经病理性痛(neuro-pathic pain),具有痛觉过敏和痛觉异常等疼痛神经可塑性特点;丝裂原活化的蛋白激酶(mitogen-activated proteins kinases,MAPKs)作为一种关键细胞信号分子,包括细胞外信号调节激酶(ERK)、p38和c-Jun氨基末端激酶(JNK)3条主要激活通路,在病理性痛觉信号转导和神经可塑性调控中起重要作用。在不同动物模型中,抑制MAPKs信号通路,可明显减轻炎症痛和神经病理性痛,这为MAPKs抑制剂开发成为治疗病理性痛的药物提供了可能,MAPKs已成为治疗病理性痛药物作用的一个重要的潜在的靶点。     

Emerging trends in the pharmacotherapy of chronic pain

The pharmacotherapy for pain is dominated by conventional analgesics such as the opioids and the non-steroidal anti-inflammatory drugs. Recent advances in the understanding of the mechanisms of pain in general and chronic pain in particular, opened the field of analgesic therapy to newer pharmacological targets, which are aimed at improved efficacy and enhanced tolerability over conventional antipain treatments. Many novel targets are still in preclinical development, but some have made it into human trials and have shown promise. Newer anticonvulsants, new generation cyclooxygenase inhibitors, better tolerated glutamate modulators and balanced serotonin/noradrenaline re-uptake inhibitors are some targets that have shown promise in the clinic. These and other compounds that are in advanced phases of development for chronic pain are reviewed in this paper. It is hoped that the decade of pain control and research will lead us to an arsenal of effective and safe analgesics that will conquer the problem of chronic pain.     

The role of 5-HT1A receptors in research strategy for extensive pain treatment

In the last few years, there has been a great increase in our understanding of pain mechanisms. Given the complexity of the mechanisms involved in pain modulation, it is surprising that the pharmacological control of pain through the application of relatively simple analgesics can be effective. Nevertheless, the application of single analgesics is not always effective in diverse painful conditions such as chronic pain syndromes. In these circumstances, we can take advantage of the complexity of pain regulation and try to identify new targets in these intricate processes. It is becoming clear that the combination of different mechanisms, which improves efficacy with reduced toxicity, is necessary for the reliable pharmacotherapy of pain, and is at the forefront in the search for better analgesics. Serotonin is involved at multiple levels in the regulation of nociception. In particular, the raphe nuclei may play a crucial role in integrating the nociceptive and affective information through descending projections to the spinal cord and ascending projections to the forebrain. In these nuclei, 5-HT1A receptors function as somatodendritic autoreceptors controlling the release of serotonin in terminal areas. Different studies have shown that, by preventing this inhibitory control of serotonin release, it is possible to enhance the analgesic effect of drugs that increase serotonin levels (i.e. antidepressants, opiates, and non-steroidal anti-inflammatory drugs) by facilitating descending, and also ascending, pathways involved in pain modulation. Therefore, 5-HT1A receptors may be used as a new target in the search for new pharmacological approaches in the augmentation of analgesia.     

Evaluation of anticonvulsants for possible use in neuropathic pain

Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development. Therefore, it is already a phenomenon that researchers turn their projects toward a larger market, related with possible similar mechanism. Anticonvulsant mechanism of action is in the first place among primary indications for drugs revealing potential analgesic activity. Therefore, many drug candidates for epilepsy, still in preclinical stage, are being evaluated for activity in neuropathic pain. This review is focusing on antiepileptic drugs, which are evaluated for their analgesic activity in major tests related with neuropathic pain. Relation between structure, mechanism of action and result in tests such as the Chung model (spinal nerve ligation SNL), the Bennett model (chronic constriction injury of sciatic nerve CCI) and other tests are considered. The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with listed animal models has been discussed.     

Postoperative pain management: a practical review, part 2.

PURPOSE: The pharmacotherapy and assessment of postoperative pain in general pharmacy practice settings are reviewed. SUMMARY: Numerous factors related to all levels of society and the health care system contribute to suboptimal treatment of postoperative pain, despite awareness of this challenge for at least the past 30 years and the availability of potent analgesics and tools to help clinicians care for persons with postoperative pain. The consequences of acute pain include clinical, economic, and patient-reported outcomes; thus, improving the treatment of postoperative pain has the potential to improve health care from a broad perspective. Opioids remain the cornerstone of treatment of postoperative pain. Multimodal analgesia also has the potential to improve the pharmacotherapy of postoperative pain. In addition to the appropriate use of drugs, it is important that clinicians be comfortable with equianalgesic dosage conversion, helping ensure that analgesic-related adverse effects are minimal, assessing pain and function, and incorporating this information into patient care. CONCLUSION: Providing optimal management of postoperative pain is a vital goal for all health care providers. There is substantial potential for pharmacists to help meet this goal.     

Postoperative pain management: a practical review, part 1.

PURPOSE: The pharmacotherapy and assessment of postoperative pain in general pharmacy practice settings are reviewed. SUMMARY: Numerous factors related to all levels of society and the health care system contribute to suboptimal treatment of postoperative pain, despite awareness of this challenge for at least the past 30 years and the availability of potent analgesics and tools to help clinicians care for persons with postoperative pain. The consequences of acute pain include clinical, economic, and patient-reported outcomes; thus, improving the treatment of postoperative pain has the potential to improve health care from a broad perspective. Opioids remain the cornerstone of treatment of postoperative pain. Multimodal analgesia also has the potential to improve the pharmacotherapy of postoperative pain. In addition to the appropriate use of drugs, it is important that clinicians be comfortable with equianalgesic dosage conversion, helping ensure that analgesic-related adverse effects are minimal, assessing pain and function, and incorporating this information into patient care. CONCLUSION: Providing optimal management of postoperative pain is a vital goal for all health care providers. There is substantial potential for pharmacists to help meet this goal.     

Current status and future directions in the pharmacotherapy of epilepsy

Considerable progress in the pharmacotherapy of epilepsy has been witnessed during the 20th century. However, despite the development of various antiepileptic drugs, about a third of patients are resistant to current pharmacotherapies. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not affect the progression or underlying natural history of the condition. Furthermore, currently there are no drugs available that prevent the development of epilepsy following, for example, head trauma. The rapid expansion of information about the cellular, molecular and genetic mechanisms of epilepsy is expected to lead to more effective therapies, prevention or even a cure for different types of epilepsy. In this article, I assess the current status of antiepileptic therapies and highlight innovative approaches for future treatments.     

Progress in acetylcholinesterase inhibitors for Alzheimer’s disease

Current pharmacotherapy of Alzheimer’s disease (AD) involves drugs that are known as acetylcholinesterase inhibitors (AChEIs), which increase the acetylcholine concentration in the brain. Although effective in improving cognitive, behavioural and functional impairments, these drugs are not able to alter disease progression. In this review, the recent patent literature on AChEIs from 2002 to early 2005 will be discussed, focusing attention on the novel analogues of the approved drugs, as well as on the most important AD therapeutic advances. The clinical efficacy of AChEIs will probably be enhanced by their combination with other drugs acting through different pharmacological mechanisms. As the neuronal loss comprises more than the forebrain cholinergic system, the weak effectiveness of AChEIs is not surprising. Besides the ‘cholinergic hypothesis’ approaches, new treatments are emerging based on multipotent compounds able to target the underlying pathogenic mechanisms of AD; these treatments are summarised herein.     

Latest research and development trends in non-insulin anti-diabetics

Type 2 diabetes mellitus, also called non-insulin dependent diabetes mellitus, is a chronic endocrine disease characterized by insulin resistance in tissues such as fat, liver and skeletal muscle, and impaired insulin secretion in pancreatic β cells. The prevalence and incidence of type 2 diabetes exploded over last decades along with increased population obesity owing to western lifestyle factors such as lack of exercise and high calorie diets. As diabetes progresses without appropriate treatment, many micro- and macro-vascular complications occur, leading to increased risk of mortality. Although lifestyle modifications including a healthier diet and more frequent exercise are suggested as initial therapy for type 2 diabetes, pharmacotherapy is required in many cases. Currently, several anti-diabetic drugs with different mechanisms of action are available, but increased effectiveness and tolerability are a still unmet need for diabetes pharmacotherapy. Thus, the development of new anti-diabetic drugs is an active research area in both academia and the pharmaceutical industry. This review focuses on the targets in the latest developments of non-insulin anti-diabetics that attract the most interest in this disease area.     

抗抑郁药用于疼痛治疗的研究进展

慢性痛或神经痛是一种临床综合征,常伴有抑郁障碍,严重影响患者生活质量.对于神经痛,常规镇痛药物、甚至麻醉性镇痛药经常无效,而抗抑郁药、抗精神病药和抗癫痫药物等则有效.本文综述了抗抑郁药用于镇痛的作用机制和不同类型的抗抑郁药在疼痛治疗中的应用,旨在为疼痛的临床治疗提供参考.