白介素-1β与术后疼痛关系的研究进展

背景 术后疼痛的形成和维持过程中存在炎症反应,白介素-1β(interleukin-1β,IL-1β)是手术创伤诱导伤口附近产生和释放的重要炎症介质,在触发疼痛信号产生痛觉敏化和疼痛的过程中发挥着重要的作用.目的 分析总结细胞因子IL-1β信号通路与术后疼痛的相关性及其机制的文献资料.内容 综述IL-1β的生物学特性及在术后疼痛中的可能作用机制和调节IL-1β信号通路对术后疼痛的影响.趋向 IL-1β在手术在创伤后的炎症过程和痛觉神经传导中发挥重要作用,在不同水平参与术后疼痛形成和维持.进一步认识其确切的细胞和分子机制,由此开发出新一代疼痛治疗药物和手段,为术后疼痛的治疗提供一个新渠道.     

白介素和神经病理性疼痛

近来实验发现免疫细胞活化对于人类和实验动物神经病理性疼痛的病因和症状有密切联系,而免疫细胞活化的一类产物--白介素在疼痛形成和维持过程中发挥重要作用.此文讨论白介素-1(白介素-1α、白介素-1β、白介素-1ra)、白介素-6和白介素-10在神经病理性疼痛的产生和维持过程的作用,探讨白介素在神经病理性疼痛治疗的前景.     

白介素-1β与胃癌关系的研究进展

目的介绍白介素-1β(IL-1β)的概况及其与胃癌关系的研究进展。方法收集近年来国内、外关于IL-1β及其与胃癌关系的相关文献并进行综述。结果 IL-1β是一种促炎性细胞因子,可以介导炎症发生、调节免疫反应、诱导基因发生表观遗传学改变等,在胃癌组织中高表达。影响IL-1β在胃癌组织中表达水平的因素包括IL-1β的基因多态性、核因子-κB的干预和幽门螺旋杆菌感染。IL-1β可以抑制胃酸分泌、诱导DNA发生甲基化改变、募集骨髓源细胞、促进胃癌血管形成及促进血管细胞黏附分子-1、细胞间黏附分子-1、CD44等黏附分子的表达,在胃癌的发生、发展和转移中均发挥了重要作用。结论靶向性地阻断IL-1β及其受体具有抑制胃癌发生的作用,有望成为胃癌治疗新的策略之一。     

乌司他丁对兔髓核细胞中诱导型一氧化氮合酶和基质金属蛋白酶表达的影响

目的 探讨乌司他丁对白介素-1β(interleukin-1β,IL-1β)诱导的兔椎间盘髓核细胞中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)和MMP-3表达的影响.方法 用酶消化法...     

术后反应性疼痛与引流液炎症因子相关性

目的探讨腰椎术后反应性疼痛与引流液中炎症因子的相关性。方法 2012年3月—7月,40例单节段腰椎椎间盘突出患者在本院行单节段腰椎后路椎板减压、椎间盘切除、椎间植骨融合内固定术。其中出现术后非切口部位的腰臀部或下肢疼痛13例。于术后1~3 d连续记录出现非切口部位疼痛的视觉模拟量表(VAS)评分。术后1~3 d连续留取伤口引流液,检测伤口局部炎症因子白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平及外周血炎症因子水平;术后1~3 d连续检测红细胞沉降率(ESR)、C反应蛋白(CRP)。通过统计学分析,探讨炎症因子与疼痛程度、ESR及CRP的相关性。结果引流液IL-1β,IL-6,TNF-α水平与术后疼痛VAS评分呈正相关,而与血液中炎症因子水平无相关性,与ESR,CRP无相关性。结论腰椎术后反应性疼痛与术后引流液中IL-1β,IL-6,TNF-α水平显著相关,提示疼痛与术后炎症因子的局部增加有密切的关系。     

白介素-6信号传递途径及其与结肠癌的关系

白介素-6(interleukin-6,IL-6)家族的特征是在其受体的组成中至少包括一个为gp130(dycopeptides 130,CD130)、具有跨膜信号传递功能的亚单位[1].     

缺氧-复氧诱导HK2细胞HMGB1/TLR-4信号通路活化调控TNF-α、IL-1β表达的意义

目的:观察缺氧-复氧诱导后HK2细胞的凋亡率、高迁移率蛋白B1(HMGB1)、Toll样受体4(TLR-4)、肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)水平的改变,探讨缺氧-复氧模拟肾缺血-再灌注诱导HGMB1/TLR-4信号通路活化在调控晚期炎症反应和细胞凋亡的意义。方法:用抗霉素A处理HK2细胞(0.1μmol/L)耗竭ATP的方法建立缺氧-复氧HK2细胞模型以模拟缺血-再灌注损伤。将HK2细胞随机分成3组:normal组、I/R组和重组人HGMB1组(r HGMB1组),在复氧后12 h、24 h、48 h 3个时间点,用流式细胞术检测细胞的凋亡率,ELISA法检测细胞上清液HMGB1、TNF-α、IL-1β的水平,免疫激光共聚焦和western blot检测HK2细胞TLR-4蛋白的表达。结果:缺氧-复氧可诱导HK2细胞凋亡比率、细胞上清液重组人HMGB1、TNF-α、IL-1β水平及HK2细胞TLR-4蛋白12 h即明显增多,24 h达高峰,与normal组相同时间点相比较,差异均有统计学意义(P<0.01)。经重组人HGMB1处理后,细胞的凋亡率、上清液HMGB1、TNF-α、IL-1β水平及HK2细胞TLR-4蛋白均明显降低,与I/R组相同时间点相比较差异均有统计学意义(P<0.01或P<0.05)。结论:缺氧-复氧模拟肾缺血-再灌注可诱导HK2细胞HGMB1/TLR-4信号通路活化,参与调控TNF-α、IL-1β炎症介质的表达及HK2细胞的凋亡,通过晚期炎症和凋亡机制介导AKI的发生和发展。     

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.     

α7烟碱型乙酰胆碱受体在重症肌无力胸腺细胞中的表达及其功能

目的 探讨重症肌无力(myasthenia gravis,MG)患者胸腺细胞中α7烟碱型乙酰胆碱受体(α7nicotinic acetylcholine receptor,α7 nAChR)的表达及其对胸腺细胞分泌细胞因子和T细胞增殖的影响。方法 选取2021年6月—2022年6月河南省人民医院重症肌无力综合诊疗中心收治的行胸腔镜下胸腺扩大切除术MG患者为MG组，另选取阜外华中心血管病医院成人心外科2021年6月—2022年9月行心脏疾病手术过程中为暴露术野行部分胸腺切除术的患者为对照组。制备MG组及对照组胸腺单细胞悬液，采用实时荧光聚合酶链式反应、蛋白免疫印迹法检测患者胸腺细胞中α7 nAChR的表达情况。采用CD3/CD28单抗偶联磁珠诱导T细胞活化，酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测胸腺细胞中细胞因子干扰素-γ(interferongamma,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-4(interleukin-4,IL-4)、IL-6、IL-10、IL...     

肾移植受者的细胞因子及其受体单核苷酸多态性与术后感染的相关性

目的探讨肾移植受者的某些细胞因子及其受体基因多态性与术后感染的相关性。方法采用自行研制的细胞因子及其受体单核苷酸多态性检测芯片,分析129例肾移植受者的肿瘤坏死因子(TNF-α)、白细胞介素10(IL-10)、转化生长因子(TGF-β1)、IL-4、IL-6及其受体的21个位点的基因多态性分布情况,并按照患者术后是否发生感染进行分组比较。结果5种细胞因子及其受体单核苷酸多态性在感染组和非感染组中分布明显不同,分别是基因型IL-6R(-183GG、G/A)、IL-10(-824C/T,-597C/A)及TNF-α(-308GG、G/A);等位基因为IL-10R1(1112G/A)、IL-6R(-183G/A)、IL-4R(1902A/G)、TNF-α(-308G/A)及TGF-β1( 869T/C)。结论基因型IL-6R(-183GG)、IL-10(-824C/T,-597C/A)及TNF-α(-308GG),等位基因IL-4R(1902A)、IL-6R(-183G)、IL-10R1(1112G)、TNF-α(-308G)及TGF-β1( 869C)是肾移植后感染的易患因素;而基因型IL-6R(-183G/A)和TNF-α(-308G/A)可能为移植后感染的非易患因素。     

Potential value of adenosine 5'-triphosphate (ATP) and adenosine in anaesthesia and intensive care medicine

Extracellular adenosine and adenosine triphosphate (ATP) areinvolved in biological processes including neurotransmission,muscle contraction, cardiac function, platelet function, vasodilatation,signal transduction and secretion in a variety of cell types.They are released from the cytoplasm of several cell types andinteract with specific purinergic receptors which are presenton the surface of many cells. This review summarizes the evidenceon the potential value and applicability of ATP (not restrictedto ATP–MgCl₂) and adenosine in the field of anaesthesiaand intensive care medicine. It focuses, in particular, on evidenceand roles in treatment of acute and chronic pain and in sepsis.Based on the evidence from animal and clinical studies performedduring the last 20 years, ATP could provide a valuable additionto the therapeutic options in anaesthesia and intensive caremedicine. It may have particular roles in pain management, modulationof haemodynamics and treatment of shock.     

The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review

There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors. Among NMDA receptor subtypes, the NR2B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.     

骨质疏松慢性疼痛的分类及其与溶酶体-VNUT-ATP的关系

骨质疏松症(osteoporosis, OP)是中老年人常见的全身代谢性骨病,目前临床医师在OP的治疗中更加关注骨密度的变化,常常忽略OP带来的疼痛,而疼痛是OP最常见、最典型的症状,其长期存在,严重影响患者的生理及心理健康。现阶段,引起OP慢性疼痛的具体机制仍未被阐明,按照病理学特征分类,疼痛可分为伤害感受性疼痛和神经病理性疼痛,其中神经病理性疼痛在OP慢性疼痛中的研究逐渐被重视,可能成为治疗OP慢性疼痛的一把新钥匙。在骨吸收活跃状态,骨与软组织会释放各种刺激因子,ATP是其中一种,同时ATP可充当神经递质,在神经元之间传导冲动,研究证实ATP的释放会导致疼痛的发生,特别是神经病理性疼痛,抑制ATP的释放可以起到抑制疼痛的作用,ATP带有高度负电荷,其释放需要特定蛋白的参与。氯膦酸盐是第一代不含氮双膦酸盐,除抗骨质疏松外,还有良好的镇痛作用。研究发现,氯膦酸盐是一种对囊泡核苷酸转运蛋白选择性强且有效的抑制剂,可以抑制ATP通过囊泡核苷酸转运蛋白进入溶酶体,进而阻断了ATP的释放,达到止痛效果。因此,溶酶体-VNUT-ATP途径在OP慢性疼痛中发挥重要作用,深入研究该途径可以为OP慢性...     

慢性非细菌性前列腺炎/慢性盆腔疼痛综合征患者前列腺液中炎症因子差异表达的临床意义

目的 探讨慢性非细菌性前列腺炎/慢性盆腔疼痛综合征(CAP/CPPS)患者前列腺液(EPS)中炎症因子差异表达的临床意义.方法选取符合CAP/CPPS诊断标准的患者EPS标本38例(CAP 18例,CPPS 20例),20例健康者EPS标本作对照.应用抗体芯片检测EPS中40种炎症因子的表达差异.结果 与对照组比较,CAP患者7种炎症因子包括单核细胞趋化因子(MCP)-1、可溶性肿瘤坏死因子受体Ⅱ(s TNF RⅡ)、血小板衍生生长因子-BB(PDGF-BB)、白细胞介素(IL)-1β、IL-11、IL-6、MCP-2表达增高了1.50倍以上,CPPS患者5种炎症因子包括MCP-1、PDGF-BB、MCP-2、s TNF RⅡ、IL-11表达增高了1.50倍以上;聚类分析结果表明,MCP-1、PDGF-BB为最后聚合的炎症因子,CAP组中分别上调3.47、2.07倍,CPPS组中分别上调2.25、2.19倍;与CPPS组比较,CAP组IL-1β,MCP-1、S TNF RⅡ表达分别上调1.85、1.55、1.67倍.结论 CAP/CPPS发病过程中炎症因子表达明显增高,CAP的炎症反应程度高于CPPS,MCP-1、PIX;F-BB有可能成为CAP/CPPS诊断的炎症标志物.     

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.     

开放式前入路腹股沟疝修补术后慢性疼痛的超声诊断

目的分析开放式前入路腹股沟疝修补术后慢性疼痛的超声诊断意义。 方法选取2009年8月至2014年5月,复旦大学附属华东医院164侧因开放式前入路腹股沟疝修补术后持续慢性疼痛病例,通过超声检查明确慢性疼痛的病因,对合并出现的各项病因进行分组比较。 结果超声检查发现引起术后慢性疼痛的阳性诊断有：包裹性积液、阴囊壁水肿、睾丸炎症、睾丸鞘膜腔积液、精索在重建内环口处活动受限、精索静脉曲张、耻骨处瘢痕增生、补片皱缩变形、补片或网塞堆积、复发疝、精索囊肿、附睾头囊肿。在两两合并出现的阳性诊断各组中,包裹性积液合并阴囊壁水肿、精索静脉曲张合并精索在重建内环口处活动受限、补片变形皱缩合并和复发疝的发生率在各自分组内存在显著差异（χ²=41.37、20.07、13.19、7.36,P均<0.05）。 结论超声检查对于开放式前入路腹股沟疝修补术后慢性疼痛的诊断具有重要价值,部分阳性诊断因病程发展常合并出现,临床医师诊断时需全面考虑。     

Vocalization responses after intrathecal administration of ionotropic glutamate receptor agonists in rats

Inotropic glutamate receptors in the spinal cord (N-methyl-D-aspartic acid [NMDA], alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kainate receptors) seem to play a key role in acute pain transmission and the neuronal plasticity in chronic pain states. Vocalization responses produced by activation of these receptors on the pain pathways can be quantified semiautomatically and thus could be used as a research tool. We studied vocalization responses induced by intrathecal administration of various agonists acting at the glutamate receptors in normal rats and in the presence of peripheral inflammation and a chronic constriction injury model of neuropathic pain. The nonselective endogenous agonist, glutamate, and the NMDA receptor glycine site agonist D-serine did not produce vocalization, whereas selective agonists acting at AMPA, NMDA, and kainate receptors produced dose-related vocalization responses. The vocalization response evoked by the administration of AMPA was significantly increased in the neuropathic pain model. In conclusion, spinal administration of ionotropic glutamate receptor agonists produce short-lasting, dose-related vocalization responses that can be used as a basic research and screening tool for analgesic studies. However, peripheral inflammation or nerve injury did not substantially alter vocalization responses overall, possibly indicating that the vocalization test is not a good tool for studying the role of excitatory amino acids in these pathological pain conditions. IMPLICATIONS: Vocalization responses evoked by spinal administration of ionotropic glutamate receptor agonists can be used for experimental analgesic studies. However, pathological pain models did not substantially alter vocalization responses, possibly indicating that this test is not suitable for studying the role of spinal excitatory amino acids in central sensitization.     

Chronic pain and comorbid depression

Opinion statement For patients with chronic pain, the experience of pain is intimately linked with psychologic distress. Epidemiologic studies indicate that depression is a common comorbidity accompanying chronic pain states. Longitudinal studies also suggest that depression can predict the emergence of chronic pain in selected populations. Emerging evidence suggests numerous pathophysiologic mechanisms that underlie the coexistence of depression and chronic pain states. Comorbid depression can complicate the presentation, clinical course, and response to treatment of patients with chronic pain. The literature reviewed herein focuses on treatment approaches applicable to chronic, nonmalignant pain states predominantly. Although antidepressants offer advantages in simultaneously producing pain relief and mitigating depression, not all antidepressants share equal efficacy; those with noradrenergic and serotonergic influences seem to fare better than agents with single neurotransmitter influences. Treatment of depression may be essential to fully enlist the patient with chronic pain in comprehensive pain management and rehabilitative approaches. Management plans of patients with chronic pain can be designed with specific individual patient needs in mind, and may involve concurrent use of antidepressants, analgesics, and psychotherapeutic approaches.     

Synovial membrane receptors as therapeutic targets: A review of receptor localization,structure, and function

Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology of many arthropathies and may be adversely affected in joint disease. Improving knowledge of the receptors present within the synovium will aid in a better understanding of joint pathology and the development of new treatments for diseases such as osteoarthritis and rheumatoid arthritis. Knowledge of the location and function of synovial membrane receptors (both in healthy and diseased synovium) may provide important targets in the treatment of various arthropathies. Classic pain receptors such as opioid receptors in the synovium are a mainstay in local and systemic management of chronic pain in many species. In addition to these, many other receptors such as bradykinin, neurokinin, transient receptor potential vanilloid, and inflammatory receptors, such as prostanoid and interleukin receptors have been discovered within the synovial membrane. These receptors are important in pain, inflammation, and in maintenance of normal joint function and may serve as targets for pharmacologic intervention in pathologic states. The goal of this review is to outline synovial membrane receptor localization and local therapeutic modulation of these receptors, in order to stimulate further research into pharmacological management of arthropathies at the local level. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1589–1605, 2017.