痛觉相关钠离子通道研究进展

疼痛是一种与组织损伤或潜在的损伤相关的不愉快的主观感觉和情感体验,是机体受到伤害性刺激后产生的一种防御反应。伤害性感觉神经元细胞膜上的电压门控钠离子通道是细胞表面一类跨膜糖蛋白,负责可兴奋细胞动作电位的产生和传导,并且在炎性痛、神经病理性疼痛和功能性痛的产生、传导以及维持上起到了重要的作用,成为近年来疼痛病理生理机制研究和疼痛治疗的分子靶标。本文将就痛觉相关钠离子通道的类型,结构,及其表达和功能的改变与疼痛的关系进行综述。     

一念放下,万般自在——能否训练自己去"遗忘"疼痛

1994年国际疼痛学会(IASP)明确定义:疼痛是一种与组织损伤或潜在损伤相关的不愉快的主观感觉和情绪体验.这个定义赋予疼痛两个方面的意义:感觉分辨(sensory discrimination)和情绪体验(affective dimensions).与躯体的其他感觉不同,除了生理上的感觉分辨,痛觉的另一个显著特征就...     

疼痛——生命的第五体征

正人体有各种各样的感觉,疼痛是不太讨人喜欢的那一种。但如同生老病死一样,疼痛又无处不在,不可避免。我们都或多或少经历过疼痛,甚至给我们的生活带来了难言的痛苦,对于疼痛这个人类的健康杀手,我们必须要关注它,认识它,了解它。疼痛是什么?疼痛是一种令人不快的感觉和情绪上的感受,伴有实质上或潜在的组织损伤,是一种主观感受。汉语的"疼"是指余痛,"痛"是指病人身体内部的伤害性感觉。"疼痛"一词来源于     

疼痛的性别差异

目前已有许多临床流行病学研究和实验研究证实了人类的疼痛存在性别差异。临床迹象表明疼痛存在性别差异,许多慢性疼痛疾病（偏头痛、颞下颌关节痛、纤维肌痛、风湿痛等）的发生率女性明显高于男性。女性对一些实验性疼痛（机械刺激痛、电刺激痛、热刺激痛等）更加敏感,痛阈和对疼痛的耐受性比男性低,而且女性月经周期与疼痛有关。啮齿动物实验研究也发现存在疼痛的性别差异。但是在不同动物研究或不同实验性疼痛刺激下雌雄性别的反应不完全相同,这些差异可能是由很多影响因素所导致的。目前许多研究对疼痛存在性别差异的解释也有所不同,机制尚不清楚,可能的因素包括：生物因素（性激素、内源性镇痛、基因等）、社会心理因素以及两者的相互作用等。     

疼痛的性别差异

目前已有许多临床流行病学研究和实验研究证实了人类的疼痛存在性别差异.临床迹象表明疼痛存在性别差异,许多慢性疼痛疾病(偏头痛、颞下颌关节痛、纤维肌痛、风湿痛等)的发生率女性明显高于男性.女性对一些实验性疼痛(机械刺激痛、电刺激痛、热刺激痛等)更加敏感,痛阈和对疼痛的耐受性比男性低,而且女性月经周期与疼痛有关.啮齿动物实验研究也发现存在疼痛的性别差异.但是在不同动物研究或不同实验性疼痛刺激下雌雄性别的反应不完全相同,这些差异可能是由很多影响因素所导致的.目前许多研究对疼痛存在性别差异的解释也有所不同,机制尚不清楚,可能的因素包括:生物因素(性激素、内源性镇痛、基因等)、社会心理因素以及两者的相互作用等.     

P2X7受体在病理性疼痛中的研究进展

病理性疼痛主要包括组织损伤或炎症引起的炎症痛、神经系统损伤或疾病引起的神经病理性疼痛和恶性肿瘤及治疗引起的癌症痛三大类。病理性疼痛对常规的镇痛药物反应不理想,迫切需要寻找新的对病理性疼痛更有效和更特异的治疗手段。P2X7受体作为离子通道型嘌呤能受体,在炎症痛、神经病理性疼痛和癌症痛中都具有重要作用。靶向P2X7受体的新药物将为病理性疼痛的治疗带来新的希望。该文综述了P2X7受体在三类病理性疼痛中的研究进展。     

活性氧在脊髓损伤性中枢疼痛敏化中作用机制的研究进展

活性氧是指氧的某些代谢产物和一些反应的含氧产物,研究证实脊髓损伤后继发产生的活性氧与中枢疼痛敏化关系密切。它可能通过激活兴奋性氨基酸受体,继而激活背角神经元中参与敏化的第二信使系统发挥作用,亦与胶质细胞活化和细胞因子、神经营养因子释放有关。本文对活性氧诱发脊髓损伤性中枢疼痛敏化的作用机制作一综述。     

小胶质细胞在神经病理性疼痛中的作用

神经病理性疼痛对患者的生理和心理健康都有着极大的影响。近几年来的研究表明,外周神经炎症或损伤激活的小胶质细胞通过表达及释放一系列介质分子,在神经病理性疼痛的产生和传递通路中发挥重要的调制作用。激活的小胶质细胞与神经元之间信息交互传递从而影响痛敏行为的这一崭新模式极大地推进了人们对于疼痛的理解。同时也为以小胶质细胞作为靶点,开辟镇痛药物治疗的新方法提供了理论依据。     

跑台运动通过调节大鼠前扣带回线粒体自噬改善神经病理性疼痛

本研究旨在考察跑台运动对神经病理性疼痛的影响,并探讨大鼠前扣带回皮质(anterior cingulate cortex, ACC)线粒体自噬在运动改善神经病理性疼痛中的潜在作用。为了探讨神经病理性疼痛对线粒体自噬的影响,采用慢性坐骨神经压迫损伤(chronic constriction injury of the sciatic nerve, CCI)方法建立神经病理性疼痛Sprague-Dawley (SD)大鼠模型。Von-Frey丝检测大鼠的机械性缩足反射阈值(paw withdrawal threshold, PWT),热辐射仪检测大鼠的热缩足潜伏期(paw withdrawal latency,PWL),qPCR检测ACC组织中线粒体自噬相关Pink1、Parkin、Fundc1、Bnip3 mRNA的表达,Western blot检测PINK1、PARKIN蛋白水平。为了探讨线粒体自噬诱导剂羰基氰化物间氯苯腙(carbonyl cyanide m-chlorophenylhydrazone, CCCP)激活线粒体自噬对CCI大鼠痛行为的影响,将24只SD大鼠随机分为CCI...     

胶质细胞与病理性疼痛

胶质细胞是中枢神经系统内的一类有别于神经元的细胞,可表达多种神经递质或细胞因子受体,在神经系统的多种功能中扮演着重要角色。组织损伤或炎症引起脊髓胶质细胞大量激活,激活的胶质细胞分泌多种细胞因子和神经-胶质兴奋物质,参与病理性疼痛的产生与维持。以胶质细胞为靶点可能为病理性疼痛的治疗另辟蹊径。     

Interrelated hypoalgesia,creep, and muscle fatigue following a repetitive trunk flexion exposure

Repetitive trunk flexion can damage spinal tissues, however its association with low back pain in the workplace may be confounded by factors related to pain sensitivity. Muscle fatigue, exercise-induced hypoalgesia, and creep-induced neuromuscular changes following repetitive trunk flexion may all affect this assumed exposure-pain relationship. This study’s purpose was to determine how mechanical pain sensitivity in the low back is affected by a repetitive trunk flexion exposure and identify factors associated with changes in low back pain sensitivity. Pressure pain thresholds, perceptions of sub-threshold stimuli, and muscle fatigue in the trunk and tibia, as well as lumbar spine creep were tracked in 37 young healthy adults before and up to 40 min after a 10-min repetitive trunk flexion exposure. Pressure pain thresholds (p = 0.033), but not perceptions of sub-threshold stimuli (p > 0.102) were associated with approximately a 12.5% reduction in pain sensitivity 10 min after completing the exposure, while creep and local muscle fatigue effects were only observed immediately following the exposure. Creep and fatigue interactions and the corresponding tibial measure co-varied with individual low back pressure pain thresholds. The net hypoalgesic effects of repetitive trunk flexion have the potential to partially mask possibly injurious loads, which could contribute to the severity or incidence of lower back injuries related to these exposures.     

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the "cuff model" of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.     

Minimising pain in farm animals: the 3S approach – ‘Suppress,Substitute, Soothe’

Recently, the French National Institute for Agricultural Research appointed an expert committee to review the issue of pain in food-producing farm animals. To minimise pain, the authors developed a ‘3S’ approach accounting for ‘Suppress, Substitute and Soothe’ by analogy with the ‘3Rs’ approach of ‘Reduction, Refinement and Replacement’ applied in the context of animal experimentation. Thus, when addressing the matter of pain, the following steps and solutions could be assessed, in the light of their feasibility (technical constraints, logistics and regulations), acceptability (societal and financial aspects) and availability. The first solution is to suppress any source of pain that brings no obvious advantage to the animals or the producers, as well as sources of pain for which potential benefits are largely exceeded by the negative effects. For instance, tail docking of cattle has recently been eliminated. Genetic selection on the basis of resistance criteria (as e.g. for lameness in cattle and poultry) or reduction of undesirable traits (e.g. boar taint in pigs) may also reduce painful conditions or procedures. The second solution is to substitute a technique causing pain by another less-painful method. For example, if dehorning cattle is unavoidable, it is preferable to perform it at a very young age, cauterising the horn bud. Animal management and constraint systems should be designed to reduce the risk for injury and bruising. Lastly, in situations where pain is known to be present, because of animal management procedures such as dehorning or castration, or because of pathology, for example lameness, systemic or local pharmacological treatments should be used to soothe pain. These treatments should take into account the duration of pain, which, in the case of some management procedures or diseases, may persist for longer periods. The administration of pain medication may require the intervention of veterinarians, but exemptions exist where breeders are allowed to use local anaesthesia (e.g. castration and dehorning in Switzerland). Extension of such exemptions, national or European legislation on pain management, or the introduction of animal welfare codes by retailers into their meat products may help further developments. In addition, veterinarians and farmers should be given the necessary tools and information to take into account animal pain in their management decisions.     

社会疼痛的神经机制

社会疼痛,指在生活中因为关系破裂、低社会评价和拒绝等负性事件引发的痛苦体验.本文从神经影像学、神经内分泌和神经免疫学等角度对社会疼痛发生的神经生理机制进行系统地阐述.未来的研究可以集中在进一步对社会疼痛和身体疼痛的关系进行阐明,对精神疾病患者(比如精神分裂症和自闭症)社会疼痛的特点和机制进行探索,以及对社会疼痛记忆加工的机制进行研究.     

New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review

Pain is an unpleasant sensory and emotional experience that is commonly associated with actual or potential tissue damage. Despite decades of pain research, many patients continue to suffer from chronic pain that is refractory to current treatments. Accumulating evidence has indicated an important role of protease-activated receptor 4 (PAR4) in the pathogenesis of inflammation and neuropathic pain. Here we reviewed PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. Understanding PAR4 and its corresponding signaling pathways will provide insight to further explore the molecular basis of pain, which will also help to identify new targets for pharmacological intervention for pain relief.     

New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review

Pain is an unpleasant sensory and emotional experience that is commonly associated with actual or potential tissue damage. Despite decades of pain research, many patients continue to suffer from chronic pain that is refractory to current treatments. Accumulating evidence has indicated an important role of protease-activated receptor 4 (PAR4) in the pathogenesis of inflammation and neuropathic pain. Here we reviewed PAR4 expression and activation via intracellular signaling pathways and the role of PAR4 signaling pathways in the development and maintenance of pain. Understanding PAR4 and its corresponding signaling pathways will provide insight to further explore the molecular basis of pain, which will also help to identify new targets for pharmacological intervention for pain relief.     

Painful Memories: Ritual and the Transformation of Community Trauma

This paper explores the question of how ritual can heal community pain or trauma. Drawing together recent insights into the ideological nature of healing with a focus on ritual process, I argue that in cases of social violence and healing, ritual's ability to assuage pain is linked to the ways in which it draws pain into the process of reconstructing memory. The argument is illustrated through an examination of how the Betsimisaraka of east Madagascar used rituals of cattle sacrifice to transform the pain they experienced during an anticolonial rebellion that took place in 1947.     

Mechanisms of ATP release in pain: role of pannexin and connexin channels

Pain is a physiological response to bodily damage and serves as a warning of potential threat. Pain can also transform from an acute response to noxious stimuli to a chronic condition with notable emotional and psychological components that requires treatment. Indeed, the management of chronic pain is currently an important unmet societal need. Several reports have implicated the release of the neurotransmitter adenosine triphosphate (ATP) and subsequent activation of purinergic receptors in distinct pain etiologies. Purinergic receptors are broadly expressed in peripheral neurons and the spinal cord; thus, purinergic signaling in sensory neurons or in spinal circuits may be critical for pain processing. Nevertheless, an outstanding question remains: what are the mechanisms of ATP release that initiate nociceptive signaling? Connexin and pannexin channels are established conduits of ATP release and have been suggested to play important roles in a variety of pathologies, including several models of pain. As such, these large-pore channels represent a new and exciting putative pharmacological target for pain treatment. Herein, we will review the current evidence for a role of connexin and pannexin channels in ATP release during nociceptive signaling, such as neuropathic and inflammatory pain. Collectively, these studies provide compelling evidence for an important role of connexins and pannexins in pain processing.     

Why is Pain Still Under‐Treated in the Emergency Department? Two New Hypotheses

Across the world, pain is under‐treated in emergency departments (EDs). We canvass the literature testifying to this problem, the reasons why this problem is so important, and then some of the main hypotheses that have been advanced in explanation of the problem. We then argue for the plausibility of two new hypotheses: pain's under‐treatment in the ED is due partly to (1) an epistemic preference for signs over symptoms on the part of some practitioners, and (2) some ED practices that themselves worsen pain by increasing patients' anxiety and fear. Our argument includes the following logic. Some ED practitioners depart from formal guidance in basing their acute pain assessments on observable features rather than on patient reports of pain. This is potentially due to an epistemic preference for signs over symptoms which aims to circumvent intentional and/or unintentional misrepresentation on the part of patients. However, conducting pain assessments in line with this epistemic preference contributes to the under‐treatment of pain in at least three respects, which we detail. Moreover, it may do little to help the practitioner circumvent any intentional misrepresentation on the part of the patient, as we explain. Second, we examine at least four ED practices that may be contributing to the under‐treatment of pain by increasing patient anxiety and fear, which can worsen pain. These practices include failing to provide orienting information and partially objectifying patients so as to problem‐solve along lines pre‐established by modern medical science. We conclude by touching on some potential solutions for ED practice.