利多卡因与神经病理性疼痛

神经病理性疼痛是一种严重影响人类健康的疼痛性疾病,至今仍缺乏有效的治疗手段,其机制也未能完全阐明.大量临床和实验研究证实,局部麻醉药利多卡因对多种神经病理性疼痛有明显的疗效.正如慢性神经病理性疼痛机制破的复杂性一样,利多卡因对慢性神经病理性疼痛的镇痛机制也不是单一的,此文就利多卡因对神经病理性疼痛镇痛机制研究的进展作一综述.     

运动皮质电刺激治疗神经病理性疼痛的研究进展

背景 神经病理性疼痛表现为慢性、顽固性疼痛,发病机制仍不十分清楚.临床疗效不佳,探讨新的治疗神经病理性疼痛的方法,越来越受到更多临床医生的关注.目前神经病理性疼痛运动皮质刺激(motor cortex stimulation,MCS)的临床应用和研究较多. 目的 探讨慢性、顽固性神经病理性疼痛安全、有效的非药物治疗方法. 内容 总结分析近20年来国外MCS临床应用及研究有关文献,探讨其方法、可能的治疗机制及研究进展,对MCS临床疗效及优、缺点进行分析. 趋向 MCS是临床上治疗慢性、顽固性神经病理性疼痛较为理想的方法,但还存在一些问题,应进行更多研究、不断改进及完善.     

交感神经纤维芽生与神经病理性疼痛

神经病理性疼痛发病机制目前尚不明确,但多数研究表明交感神经纤维芽生在神经病理性疼痛中具有重要作用.研究表明,周围神经损伤后背根神经节内感觉神经元周围出现交感神经纤维芽生并形成篮状结构,使感觉神经元与交感神经元之间产生交感-感觉耦联,这种交感-感觉耦联是产生神经病理性疼痛的形态学基础;通过药物或手术方式阻滞交感神经纤维芽生,可明显缓解神经病理性疼痛.该文就交感神经纤维芽生与神经病理性疼痛关系研究进展作一综述.     

巨噬细胞在神经病理性疼痛中的作用

神经病理性疼痛（neuropathic pain, NP）是指由躯体感觉系统的损害或疾病导致的疼痛。NP的发病机制复杂,与免疫调节有关。巨噬细胞是体内重要的免疫细胞,在体内通过自身极化和神经免疫相互作用参与神经损伤后的外周及中枢敏化形成过程,促进NP的发展。文章对巨噬细胞在NP中的作用进行综述,研究巨噬细胞在NP形成与...     

神经病理性疼痛86例临床分析

目的分析神经病理性疼痛的常见临床类型及治疗方法。方法将86例神经病理性疼痛分为周围性神经病理疼痛和中枢性神经病理疼痛,并根据其临床类型给予相应的药物治疗。结果 86例神经病理性疼痛治愈68例,占79.1%,有效13例,占15.1%。结论神经病理性疼痛的治疗应首先查明病因,应用药物,结合理疗、针灸、心理治疗以及康复治疗等综合措施。     

黑皮质素受体在神经病理性疼痛中的介导作用

国际疼痛研究会将神经病理性疼痛定义为:“原发或原发病灶引发的或神经系统的功能障碍所引起的疼痛”[1]。神经系统内的损伤或功能障碍,被认为是外周神经病理性疼痛或中枢性疼痛的主要病因。Dvorkin[2]认为神经病理性疼痛即是通常所指的慢性疼痛,即持续超过3个月或在疾病治愈后持续时间超出正常范围的疼痛。感染、创伤、机体代谢性疾病、恶性肿瘤的化疗、外科手术、射线、神经毒性药物、神经受压、炎症和肿瘤的侵袭都可以引起外周神经病理性疼痛和中枢神经病理性疼痛。神经病理性疼痛的发病率近年来有逐渐增加的趋势。原因主要在于以下几方…     

炎症因子参与神经病理性疼痛-抑郁共病的研究进展

背景 神经病理性疼痛与抑郁症共病严重影响了患者的生活质量.近年来研究发现,炎症因子在神经病理性疼痛抑郁共病发病中起重要作用.目的 综述炎症因子参与神经病理性疼痛抑郁共病的研究进展,为该病的有效防治提供参考 内容 神经病理性疼痛与感觉系统的功能障碍相关,它包括触诱发痛、痛觉过敏、自发痛等一系列疼痛症状.抑郁症表现为心境低落和厌恶活动.小胶质细胞激活后,释放的炎症因子如TNF-α、IL-6、IL-1β,通过结合5-羟色胺受体、谷氨酸盐受体、γ-氨基丁酸能受体及激活下丘脑-垂体-肾上腺素轴促进神经病理性疼痛和抑郁症的发生.趋向 炎症因子可能是治疗神经病理性疼痛-抑郁共病的靶标.     

细胞因子和胶质细胞在神经病理性疼痛中的作用

在神经病理性疼痛的机制研究中,许多学者发现神经免疫及神经系统炎症反应是造成疼痛的重要原因之一.其中,细胞因子和胶质细胞激活在疼痛的产生和维持中起到非常重要的作用.因而它们有可能成为治疗神经病理性疼痛的新的靶点.     

甲基化修饰与神经病理性疼痛

<正>神经病理性疼痛是一种由躯体感觉神经系统病变或疾病造成的疼痛,其病因多变,症状复杂,治疗效果不理想,这与其机制的复杂性有关。研究表明表观遗传调控参与神经病理性疼痛发生发展的过程[1]。甲基化修饰作为表观遗传学的重要组成部分,在神经病理性疼痛中发挥重要作用。本文就有关甲基化修饰在神经病理性疼痛中发挥作用的相关研究作一综述。甲基化的概念甲基化是指在底物中添加甲基集团的反应,包括DNA     

一氧化氮在神经病理性痛大鼠脊髓敏化中的作用

目的 评价一氧化氮(NO)在神经病理性痛大鼠脊髓敏化中的作用.方法 成年雄性Wistar大鼠32只,体重200～300 g,随机分为4组(n=8):假手术组(S组)、假手术预先给药组(S-N组)、坐骨神经慢性压迫性损伤(CCI)组和CCI预先给药组(CCI-N组).建立CCI致神经病理性痛模型,S-N组和CCI-N组分别于模型制备前鞘内注射10 μl(250 μg)NC-硝基-L-精氨酸-甲基酯,分别于术前和术后3 d测定热痛阈,于术后4、7 d各处死4只大鼠,取L4,5脊髓,测定脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(pCREB)表达水平.结果 各组术后3 d热痛阈较基础值均降低(P＜0.05);与S组和S-N组比较,CCI组热痛阈降低,脊髓背角pCREB表达上调(P＜0.05),CCI-N组上述指标差异无统计学意义(P＞0.05);与CCI组比较,CCI-N组热痛阈升高,脊髓背角pCREB表达下调(P＜0.05).结论 NO参与神经病理性痛大鼠脊髓敏化,其作用机制与促进脊髓背角pCREB释放有关.     

The genesis of pain

This article explores mechanisms that may generate pain as a multidimensional and embodied construct rather than a simple sensory state. Existing models of pain will be reviewed alongside dynamic functional imaging data and contemporary cognitive neuroscience principles, including Bayesian predictive processing, to provide a potential explanation of chronic pain states. The focus is upon an exploration of integrated cortico-limbic processing as opposed to peripheral and central sensitization.     

Immunohistochemical observations on spinal tissue innervation. A review of hypothetical mechanisms of back pain.

Immunohistochemical studies support earlier reports of a rich nerve supply to the posterior longitudinal ligament, a less developed innervation of the anterior ligament and the outermost annular ring, and a total lack of innervation in deeper parts of the intervertebral disc. Whether this pattern of innervation is altered when the disc becomes severely degenerated is presently uncertain. Recent studies have also revealed neuropeptide-immunoreactive nerves in the outermost parts of the annulus and adjacent peridiscal ligaments. These nerves are probably involved in discogenic back pain, and may become sensitized when disc tissue is injured. This sensitization appears to be coupled to an alteration of neuropeptide pools in the nearby dorsal root ganglion, the important site of neuropeptide production. Direct influences on the dorsal root ganglion, mechanical and/or chemical, may also be important, and may be involved in spinal segment degeneration.     

The anatomy and physiology of pain

Pain is an unpleasant experience that results from both physical and psychological responses to injury. A complex set of pathways transmits pain messages from the periphery to the central nervous system, where control occurs from higher centres. Primary afferent pain fibres synapse with second-order neurons in the dorsal horn of the spinal cord. Ascending spinothalamic and spinoreticular tracts convey pain up to the brain, where pain signals are processed by the thalamus and sent to the cortex. Descending tracts, via the midbrain periaquaductal grey and nucleus raphe magnus, have a role in pain modulation. When nerves are damaged, neuropathic pain results and various mechanisms have been proposed for how this takes place. These mechanisms involve both peripheral and central sensitization.     

The anatomy and physiology of pain

Pain is an unpleasant experience which results from both physical and psychological responses to injury. A complex set of pathways transmits pain messages from the periphery to the central nervous system, where control occurs from higher centres. Primary afferent pain fibres synapse with second-order neurons in the dorsal horn of the spinal cord. Ascending spinothalamic and spinoreticular tracts convey pain up to the brain, where pain signals are processed by the thalamus and sent to the cortex. Descending tracts, via the midbrain periaquaductal grey and nucleus raphe magnus, have a role in pain modulation. When nerves are damaged, neuropathic pain results and various mechanisms have been proposed for how this takes place. These mechanisms involve both peripheral and central sensitization.     

Anatomy,physiology and pharmacology of pain

Although there is an anatomical framework that is involved in pain processing, this system is not ‘hard wired’ but undergoes changes affecting the sensitivity and the ‘gain’ of nociception. Peripheral sensitization contributes to increasing afferent barrage to the spinal cord. It is mediated by many diverse elements, including nerve and immune cells, in a complex array of algogenic products. Numerous receptors and ion channels are involved. Continuing increased input into the spinal cord causes further changes of central sensitization. The glutamate receptor, N-methyl-d-aspartate (NMDA) is pivotal to these processes. The NMDA receptor is therefore a potential target for analgesic therapy. Visceral pain shares the features of the pain mechanisms described in this article, but there are some anatomical, physiological and biochemical differences to somatic pain. Damage to nerves causes changes in excitability, which induce similar peripheral and central sensitization processes that contribute to neuropathic pain. Knowledge of all these processes identifies not only a rationale for standard pain treatments but also novel potential analgesic targets. However, these systems display complex interactions and, rather than targeting a single moiety, a multi-mechanistic approach to analgesia is required.     

Antagonism of nerve growth factor-TrkA signaling and the relief of pain

Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.     

Recent topics in the management of pain: Development of the concept of preemptive analgesia

Recent studies concerned with the relationship between injury responses and acute and chronic pain were reviewed. Basic and clinical studies of pain have revealed that a large proportion of the mechanisms that produce strange signs and symptoms, such as allodynia, hyperalgesia and hyperpathia, after tissue injury are ascribed to increased excitability, or to sensitization derived from biological changes in spinal dorsal horn cells subjected to excessive noxious stimuli from injured tissues. Preemptive analgesia has been under consideration as a means of preventing the predictable sensitization to pain that follows surgery. The findings of many clinical investigations, however, remain controversial. This report discusses the importance of preemptive analgesia including the possibilities of prevention, and of extension to the control, of chronic pain syndromes.     

The adrenergic pharmacology of sympathetically-maintained pain.

The authors seek to highlight some of the recent advances in understanding the pharmacology and pathophysiology of sympathetically-maintained pain, and to develop alternate, and possibly more specific, diagnostic tests for this phenomenon. Mechanical hyperalgesia in sympathetically-maintained pain can be explained by central sensitization so that the activation of A-beta mechanoreceptors now causes pain. The sensitization of central pain-signaling neurons is dynamic and reversible. The authors propose that an ongoing input from peripheral nociceptive afferents is necessary to maintain central sensitization. This nociceptive input may be due to an alpha-adrenoceptor mediated excitatory action of sympathetic efferents on sensory nerves that is independent of neurovascular transmission.     

Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats

BACKGROUND: Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA) receptor-gated ion channels, which are usually blocked by magnesium plugs. As magnesium-deficient rats develop a mechanical hyperalgesia and intrathecal or intraperitoneal magnesium suppresses neuropathic pain, the magnesium concentrations in serum and cerebrospinal fluid may be altered in neuropathic pain. We therefore compared the magnesium concentrations in serum and cerebrospinal fluid of neuropathic rats with those in injured rats without symptoms of neuropathic pain and normal rats. METHODS: Mechanical allodynia was induced in male Sprague-Dawley rats by tight ligature of the left lumbar fifth and sixth spinal nerves. The threshold of paw withdrawal was evaluated by the up-down method using withdrawal response to stimulus with a von Frey filament on the third, seventh and 14th days. Rats with a threshold of less than 4 g were selected as the symptomatic group and compared with an asymptomatic group, an unoperated control group and a sham-operated group. On the 16th day, the Mg2+ concentrations in serum and cerebrospinal fluid were measured. RESULTS: The magnesium concentrations in the serum and cerebrospinal fluid of symptomatic neuropathic rats did not differ from those in the injured rats without symptoms of neuropathic pain, sham-operated rats and normal rats. CONCLUSION: Our results suggest that physiologic homeostasis is maintained by active transport through the blood-brain barrier despite the activation of NMDA receptor-gated ion channels. However, rats with neuropathic pain may be in a magnesium-deficient condition at the effector site, such that magnesium treatment can decrease neuropathic pain.     

Cell and molecular approaches to the attenuation of pain after spinal cord injury

Recent experimental research to treat spinal cord injury (SCI) pain has greatly increased our understanding of how such chronic pain might be modulated in the human population. Neuropathic pain is caused by the structural and biochemical changes associated with the peripheral and central nervous system damage associated with nervous system trauma, often leading to an imbalance in endogenous excitatory and inhibitory spinal systems that modulate sensory processing. But current pharmacological therapies are often ineffective over time for the greater number of patients. Although there are a variety of useful surgical and pharmacologic interventions (including electric stimulation, implantable mechanical pumps and a myriad of drugs for pain relief) cell and molecular technologies are a new frontier in pain medicine. These other potential therapeutic agents of pain are based on current and developing treatment strategies elucidated from recent research, especially concerning central spinal sensitization, and the spinal mechanisms that are thought to be the origin and ongoing cause of chronic pain, even when the injury is peripheral in location. Newly developing translational strategies such as molecular agents, viral-mediated gene transfer or cellular transplants to treat chronic pain are being evaluated in a variety of peripheral and central injury models. They seek to address both the causes of neuropathic pain, to interfere with its development and maintenance over time, and give the injured person with pain an improved quality-of-life that allows them to better deal with the larger tasks of daily life and the strenuous rehabilitation that might also improve motor function after SCI.