小胶质细胞与三磷酸腺苷在疼痛中的作用

大量证据表明,细胞内外三磷酸腺苷(adenosine 5'-triphosphate,ATP)在疼痛信号转导中起着重要作用.目前研究主要集中在ATP及其受体在慢性疼痛(尤其是神经病理性疼痛)中的作用及其可能机制.机体受到刺激后,激活的小胶质细胞会高表达P2X4受体和其他ATP受体,从而释放脑源性生长因子(brain-derived neurotrophic factor,BDNF)、白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-a,TNF-α)和一氧化氮(nitric oxide,NO).了解这些ATP受体的重要作用将为慢性疼痛治疗提供新的策略.     

CC类趋化因子亚家族在神经病理性疼痛中的作用机制

背景 现有的药物对慢性疼痛的治疗效果不佳且副作用较大,因而需要寻找新的、安全有效的治疗方法.而最近研究发现,趋化因子及其受体在慢性疼痛的发生发展中起着重要的作用. 目的 综述趋化因子在慢性疼痛尤其是神经病理性疼痛中的作用机制. 内容 就趋化因子家族CC类亚家族参与疼痛调控的相关研究进行综述,阐述其在神经病理性疼痛发生发展中的可能作用机制. 趋向 越来越多的学者发现CC类亚家族参与神经病理性疼痛的发生发展,其有望成为临床上治疗慢性疼痛的一个新靶点.     

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…     

离子通道与神经病理性疼痛

神经病理性疼痛是由神经系统损伤所致的一种慢性疼痛,发病机制复杂.已经证实异位放电是痛觉异常的电生理学基础,并且离子通道改变是形成异常放电的主要原因.就现有文献报道的感觉神经元中一些重要离子通道在神经病理性疼痛中的变化作一简单综述.     

Pannexin1在慢性神经病理性疼痛中的作用研究进展

慢性神经病理性疼痛（neuropathic pain, NP）是一种难治性疼痛,患者长期承受着巨大的痛苦,然而其治疗效果欠佳,严重降低患者的生活质量,也直接或间接地给患者家庭和社会带来沉重的经济负担。Pannexin1（Panx1）是一种新型缝隙连接蛋白,在神经系统中表达丰富,介导ATP的释放。动物实验证据表明,Pan...     

神经病理性疼痛中阿片类药物的应用

阿片类药物作为一种较为有效的药物用来治疗重度疼痛以及包括神经病理性疼痛在内的慢性疼痛.然而在神经病理性疼痛中,阿片类药物的疗效存在争议.长期持续的运用阿片类药物容易产生耐受的现象,表现为需要增加药物剂量来维持疼痛的缓解程度.但最近的几个研究都表明阿片类药物在神经病理痛中的应用是有效的.现就神经病理性疼痛中阿片类药物的耐受及应用发展作一阐述.     

情绪释放疗法对糖尿病周围神经病理性疼痛患者的影响

目的 探讨缓解糖尿病周围神经病理性疼痛、提高生活质量的有效干预方法.方法 将90例糖尿病周围神经病理性疼痛患者随机分成对照组和观察组各45例,对照组给予常规护理,观察组在对照组基础上增加情绪释放疗法,每次10～15 min,2次/d,连续8周.结果 干预后观察组疼痛灾难化、疼痛恐惧、疼痛程度得分显著低于对照组,生活质量得分显著高于对照组(均P＜0.01).结论 情绪释放疗法能有效缓解糖尿病周围神经病理性疼痛患者疼痛状况,提高患者生活质量.     

阿仑膦酸钠抑制骨巨细胞瘤细胞生长和诱导其凋亡的研究

[目的]骨巨细胞瘤是一种潜在的恶性病变，具有手术后易复发的特点。二膦酸盐是抗骨质疏松药，可以抑制破骨细胞性骨吸收，近来发现其还有抗肿瘤作用。本研究是探讨第3代二膦酸盐——阿仑膦酸钠是否能够抑制骨巨细胞瘤细胞生长，诱导骨巨细胞瘤细胞凋亡，探讨应用二膦酸盐能否成为一个防止骨巨细胞瘤复发的方法。[方法]在体外培养骨巨细胞瘤细胞，给予不同浓度的阿仑膦酸钠，作用不同时间后，应用M1Tr法检测骨巨细胞瘤细胞的活性是否受到抑制，TUNEL染色法观察骨巨细胞瘤细胞经药物作用后是否发生凋亡，流式细胞术检测凋亡率，观察药物作用后凋亡蛋白Caspase-3活性的表达是否增加。[结果]经阿仑膦酸钠作用后瘤细胞活性减低，可以发现阿仑膦酸钠抑制骨巨细胞瘤细胞生长的作用可以随时间和浓度的增加而增高。TUNEL法观察到瘤细胞凋亡染色阳性，流式细胞仪检测阿仑膦酸钠作用后骨巨细胞瘤细胞的凋亡率也随着时间和浓度的增加而增高。进一步检测随着阿仑膦酸钠浓度的提高，骨巨细胞瘤细胞的Caspase-3活性表达也增加。[结论]阿仑膦酸钠对于体外培养的骨巨细胞瘤细胞的活性有抑制作用，可以抑制其生长并诱导肿瘤细胞内的Caspase-3活性表达，促其凋亡，阿仑膦酸钠可能成为治疗和预防骨巨细胞瘤复发的一个治疗方法，但还需要进一步的体内实验研究。     

外周神经病理性疼痛的病理生理学：免疫细胞和分子机制

外周神经系统损伤常常导致慢性神经病理性疼痛，其特征表现为自发痛、痛觉过敏以及痛觉异常。这种疼痛状态常使患者极度虚弱且难以治疗。虽然人们一般认为炎性疼痛和神经病理性疼痛综合征的本质是不同的，但是显现出来的一些现象却与这一严格的分类不符。炎症极具特征性，涉及一系列不同的免疫细胞，如肥大细胞、中性粒细胞、巨噬细胞以及T淋巴细胞。此外，这些细胞还释放多种致痛复合物。最近研究表明，免疫细胞在外周神经病理性疼痛中起到了一定作用。本综述阐述了不同类型免疫细胞在外周神经病理性疼痛中的作用，及其致痛过程中释放出来的一些关键因子。     

神经调节蛋白1在慢性疼痛中的研究进展

背景 神经调节蛋白1 (neuregulin 1,NRG1)是一类表皮生长因子家族的成员,其在神经元及胶质细胞的生长发育及迁移等方面起着关键作用,但在成熟的神经系统及慢性疼痛中的作用却不甚清楚. 目的 阐述NRG1介导慢性疼痛的最新研究进展,并对其在疼痛中作用的研究提出展望. 内容 简述NRG1及其受体的功能以及在疼痛领域中作用的研究.趋向 NRG1通过复杂的机制参与了神经病理性疼痛的发生发展,有望为临床提供新的治疗靶点.     

Pain-relieving effects of intravenous ATP in chronic intractable orofacial pain: an open-label study

PURPOSE: Chronic orofacial pain is often refractory to conventional pain therapies. We conducted an open-label study to determine whether adenosine 5'-triphosphate (ATP) could alleviate chronic intractable orofacial pain, and if so, which type of pain could respond to ATP. METHODS: In 8 and 16 patients with non-neuropathic and neuropathic intractable orofacial pain, respectively, ATP was intravenously infused at a rate of 100 microgxkg(-1)xmin(-1) over 120 min. The magnitudes of spontaneous pain and brush-evoked allodynia were graded with a visual analog scale (VAS). When a VAS score for spontaneous pain was decreased by 50% or more by ATP, the patient was classified as a responder. RESULTS: The patients could be clearly divided into 10 responders and 14 non-responders. Ten of the 16 patients (62.5%) with neuropathic pain, but none of the 8 patients with non-neuropathic pain, responded to ATP. In particular, all of 8 patients with neuropathic pain following pulpectomy, with or without subsequent tooth extraction, responded to ATP. In the 10 responders, VAS scores for spontaneous pain decreased slowly but progressively during the infusion period, and eventually, ATP reduced the VAS scores for spontaneous pain and allodynia by 82 +/- 15% and 74 +/- 9%, respectively. In these responders, the analgesic and anti-allodynic effects of ATP outlasted the infusion period for medians of 7 and 12 h, respectively. CONCLUSION: Intravenous ATP did not relieve non-neuropathic orofacial pain. However, it exerted slowly expressed but long-lasting analgesic and anti-allodynic effects in patients with neuropathic orofacial pain, especially in those suffering from neuropathic pain following pulpectomy and/or tooth extraction.     

Clinical application of adenosine and ATP for pain control

This review summarizes clinical application of adenosine and adenosine 5′-triphosphate (ATP) in pain conditions. Investigations have been performed in patients with acute perioperative pain or chronic neuropathic pain treated with intravenous adenosine or ATP, or intrathecal adenosine. Characteristic central adenosine A1 receptor-mediated pain-relieving effects have been observed after intravenous adenosine infusion in human inflammation/sensitization pain models and in patients with chronic neuropathic pain. Adenosine compounds, in low doses, can reduce allodynia/hyperalgesia more consistently than spontaneous pain, suggesting that these compounds affect neuronal pathophysiological mechanisms involved in central sensitization. Such pain-relieving effects, which are mostly mediated via central adenosine A1 receptor activation, have a slow onset and long duration of action, lasting usually for hours or days and occasionally for months. With acute perioperative pain, treatment with a low-dose infusion of adenosine compounds and the A1 receptor-mediated central antisensitization mechanisms may play only a minor part in the total perioperative pain experience. By administering sufficient doses of adenosine compounds during surgery, however, significant and long-lasting perioperative pain relief can be achieved via central A1 receptor-mediated antinociceptive/analgesic actions as well as via peripheral A2a or A3 receptor-mediated antiinflammatory actions. Thus, adenosine compounds have significant potential for alleviating various types of pain.     

阿米替林在治疗神经病理性疼痛中作用机制研究和进展

背景 阿米替林(amitriptyline,AMI)是三环类抗抑郁药(tricyclic antidepressants,TCAs)在神经病理性疼痛(neuropathic pain,NPP)中应用最广泛的药物,历年文献分析总结证实TCAs对NPP有效,其中证据最确切的是AMI,并且其镇痛作用独立于抗抑郁作用,尤其适用...     

Reassessment of the role of cannabinoids in the management of pain

PURPOSE OF REVIEW: The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans. RECENT FINDINGS: Very few clinical trials looking at the analgesic effects of cannabinoids in the acute pain settings have been performed. Three recent studies have evaluated the oral administration of synthetic cannabinoids in postoperative pain. At low doses cannabinoids are not different from placebo, whereas at high doses they may be associated with adverse effects or even worsening of pain intensity. In chronic pain patients, the safety and analgesic efficacy of a number of cannabinoid compounds have recently been evaluated in several clinical trials in several chronic pain conditions. While the small size of the trials and the relatively short duration of follow-up limits broad generalization, to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS. SUMMARY: The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.     

Calcitonina como agente analgésico: revisão dos mecanismos de ação e das aplicações clínicas

Background and objectivesCalcitonin is a polypeptide hormone regulating the metabolism calcium in the body. For many years calcitonin has been used to maintain and improve bone mineral density and to reduce the fracture rate. Many studies showed that calcitonin had analgesic role in several painful circumstances. This pain‐ameliorating effect is irrelevant to its osteoclastic inhibitory effect and mechanisms like altering Na+ channel and serotonin receptor expression or hypothesis including the endorphin‐mediated mechanism were used to explain this effect. In this study we performed a thorough review on the role of calcitonin as an analgesic agent in different scenarios and investigated the fact that calcitonin can be a feasible medication to relieve pain.MethodMany studies focused on the analgesic effect of calcitonin in several painful circumstances, including acute pains related to vertebral fractures, metastasis, migraine and reflex sympathetic dystrophy as well as neuropathic pains related to spinal injuries or diabetes, and phantom pain. Also, calcitonin was showed to be a useful additive to local anesthesia in the case of controlling postoperative pain or trigeminal neuralgia more effectively. However we faced some contradictory data for conditions like lumbar canal stenosis, complex regional pain syndrome, phantom pain and malignancies.ConclusionThis study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.     

Voltage-gated sodium channels in nociception and their potential as targets for new drugs in treatment of chronic neuropathic pain

Voltage-gated sodium channels are important in the pathophysiology of chronic neuropathic pain and as targets for analgesic drugs. This review will cover the molecular structure and signalling roles for this ion channel super-family with a focus on the channels thought to be involved in nociception. We highlight the mode of action of current analgesic drugs and the difficulty of treating chronic inflammatory or neuropathic pain states. The discovery of key channel classes, or familial mutations, associated with chronic pain syndromes has resulted in intensive drug discovery programmes. The quest for selective drugs or toxins which safely and effectively block diseased channels without interfering with normal conduction in the central or peripheral nervous system has been frustratingly difficult. Nevertheless new small molecule drugs or channel selective toxins are in the development pipeline. It remains to be seen whether these will represent a significant development in the safe and effective treatment of chronic pain states.     

A ação analgésica da lidocaína intravenosa no tratamento da dor crônica: uma revisão de literatura

BackgroundPain is a public health problem, greatly impairing quality of life. Almost 80% of patients with chronic pain reported that their pain interferes with activities of daily living, and two thirds reported that the pain causes negative impact on their personal relationships. The physical and functional disability, whether temporary or permanent, compromises the professional activity and causes work absenteeism, increasing costs of health systems.ObjectivesThe aim of this review is to analyze, based on the literature, the analgesic effect of lidocaine administered intravenously for the treatment of chronic pain and to evaluate the reduction of pain intensity in patients with chronic pain, focusing on musculoskeletal and neuropathic etiology.MethodologyThe method used was a review of the literature, consisting in searching the scientific literature on the efficacy of intravenous lidocaine infusion in the treatment of patients with chronic pain.ContentOf the 19 studies reviewed, 12 had results that confirm the analgesic effect of intravenous lidocaine in patients with chronic pain. Most authors used doses of 5 mg/kg infused for 30 minutes or more, producing significant analgesia with variable duration (minutes to weeks).ConclusionsBased on the literature review, it is not possible to uniformly specify the most effective and safe dose of lidocaine administered intravenously for the treatment of neuropathic or musculoskeletal pain. As for effectiveness, the intravenous infusion of lidocaine as an alternative for the treatment of chronic pain of various etiologies seems very promising, but further studies need to be conducted.     

Intrathecal implants of microencapsulated xenogenic chromaffin cells provide a long-term source of analgesic substances

Adrenal medullary chromaffin cells secrete several neuroactive substances including catecholamines and opioid peptides that produce analgesic effects in the central nervous system. This study was designed to investigate whether intrathecal microencapsulated chromaffin cells could release analgesic materials producing antiallodynic effects on the chronic neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Prior to intrathecal implantation, chromaffin cells were encapsulated with alginate and poly-L-lysine to protect them from the host immune system. Behavior tests were performed before CCI, 1 week later, and at 4, 7, 14, 21, 28 days postimplantation. At the end of study, we performed cerebrospinal fluid (CSF) collection and implant retrieval. We observed that intrathecal implantation of encapsulated xenogenic chromaffin cells reduced the mechanical and cold allodynia in a model of neuropathic pain. CSF levels of catecholamines and metenkephalin in the rats that received implants were higher than the controls. In addition, we observed chronic survival of implants. These results suggested that intrathecal microencapsulated chromaffin cells may represent a new approach to chronic neuropathic pain management.     

The long-term effect of repeated intravenous lidocaine on central pain and possible correlation in positron emission tomography measurements

Functional neuroimaging suggests that similar brain regions are involved in the processing of pain in healthy subjects and in patients with chronic neuropathic central pain. We present a patient with chronic neuropathic central pain due to a unique lesion to the trigeminal and spinothalamic pathway who had persistent pain relief after repeated IV lidocaine infusions. Positron emission tomography scan results showed a relative hypoactivity of the left posterolateral thalamus before treatment which disappeared after therapy. This case may suggest a stereo-selective analgesic effect of lidocaine accompanied by regional cerebral blood flow changes in the thalamus, indicating that sodium channels could, in fact, be highly expressed or modified in the thalamus after thalamic deafferentation. IMPLICATIONS: We present a case of persistent central pain after encephalitis in a patient who had long-term pain relief after a series of IV lidocaine infusions. A positron emission tomography scan study, done before and after treatment, suggested that lidocaine for the diagnosis of chronic neuropathic pain may have a specific site of action in the brain.