组蛋白修饰调节异常在病理性疼痛中的作用

背景 组蛋白修饰是表观遗传学的一项重要内容.近年来研究证实组蛋白修饰调节异常在病理性疼痛的发生发展中起重要作用. 目的 阐述组蛋白修饰调节异常在病理性疼痛产生和维持中作用的研究进展,为病理性疼痛的治疗提供新思路. 内容 讨论组蛋白修饰、组蛋白乙酰化、组蛋白甲基化与病理性疼痛的关系以及组蛋白去乙酰化酶(histonedeacetylase,HDAC)抑制剂对病理性疼痛的治疗作用. 趋向 鉴于组蛋白修饰调节异常在病理性疼痛的重要作用,组蛋白修饰的调节将为病理性疼痛的治疗提供新的策略.     

miRNAs的异常表达与前列腺癌

微小RNA(miRNAs)是一族内源性非编码单链小RNA,通过结合靶基因mRNA的3'端非翻译区在转录后水平负性调节基因的表达。研究发现某些miRNAs的异常表达与前列腺癌(PCa)等多种肿瘤的发生密切相关,通过分析PCa组织、PCa患者血清和PCa细胞株中多种miRNAs的异常表达,并探讨其具体机制,可为临床PCa的诊断及治疗提供新的理论依据。     

疼痛调控相关miRNAs的筛选及脊髓miR-29c对神经病理性痛大鼠痛阈的影响

目的通过microRNAs(miRNAs)芯片技术筛选疼痛调控相关的miRNAs,观察microRNA-29c(miR-29c)对神经病理性痛大鼠痛阈的影响。方法实验一:雌性SD大鼠,随机分为神经病理性痛组(SNI组)及妊娠神经病理性痛组(PSNI组),测定机械缩足阈值(MWT),观察分娩对疼痛的影响。在SNI组及PSNI组大鼠分娩后MWT差异显著时,取脊髓腰膨大组织,筛选差异表达的miRNAs。实验二:选取目的miRNAs,包被过表达或沉默慢病毒,脊髓内注射干预后观察SNI组大鼠MWT变化。结果与SNI组大鼠比较,PSNI组大鼠分娩后第3天MWT明显升高,脊髓c-Fos蛋白含量明显降低(P0.05);miRNAs芯片分析共发现71条差异表达的miRNAs,在PSNI大鼠显著上调37条,显著下调34条;选取并包被miR-124a过表达、miR-29c沉默慢病毒注射,miR-29c表达沉默可明显提高SNI组大鼠MWT。结论 miR-29c是通过基因芯片筛选获得的miRNA,下调SNI大鼠脊髓miR-29c表达,能够显著改善病理性痛状态。     

miRNAs在前列腺癌激素非依赖性进展中的研究

微小RNA(miRNAs)是一族内源性非编码单链小RNA,通过结合靶基因mRNA的3'端非翻译区在转录后水平负性调节基因的表达。研究发现某些miRNAs(miR-221/222、146a和miR-125b等)的异常表达与前列腺癌激素非依赖性进展密切相关,通过分析激素非依赖性前列腺癌(AIPC)患者的细胞株、组织和血清中多种miRNAs的异常表达,并探讨其具体机制,可为临床AIPC的诊断及治疗提供新的理论依据。     

宫颈癌相关microRNAs表达调控机制的研究进展

宫颈癌是世界范围内三大妇科肿瘤之一,其高致死率严重威胁着女性的健康。microRNAs(miRNAs)是一类内源性非编码蛋白的、长度约为18~25个核苷酸的小RNA,在转录后水平调控靶基因的表达。现已证实miRNAs的异常表达与宫颈癌的发生发展密切相关。宫颈癌中调控miRNAs异常表达的研究报道相对较少,调控机制也不十分明确。有研究表明,表观遗传修饰、人乳头瘤病毒(HPV)、miRNAs海绵及miRNAs的多态性均可以对宫颈癌中miRNAs的表达及其功能产生影响。本文拟从这四个方面对miRNAs的表达调节以及所引起的宫颈癌发生发展的角度展开综述。     

肿瘤相关microRNAs的研究进展

微小RNA(miRNAs)为小分子非编码单链RNA片段,约22~24个核苷酸长度,通过与绑定的mRNA 3’端非翻译区的碱基配对调控mRNAs的翻译和降解,在基因表达的转录后调控中发挥功能。miRNAs可参与生命过程中的一系列重要进程,包括早期胚胎发育、细胞增殖、细胞凋亡,甚至可通过miRNAs途径调节干细胞的分化。异常miRNAs表达与肿瘤等许多疾病密切相关,自2002年首先发现miRNAs表达异常与肿瘤有关以来,关于miRNAs在肿瘤发生和耐药产生中的重要作用得到了迅速的发展。然而,全面认识了解miRNAs及其与人类肿瘤的关系仍有很长的路要走。该文简要对miRNAs生物起源以及在肿瘤发生和耐药性形成中的作用进行综述,阐述了miRNAs作为分子标志物或者新型的治疗手段在肿瘤治疗中的作用。     

MicroRNAs在Graves病中的诊断价值、作用及调控机制的新进展

毒性弥漫性甲状腺肿(GD)是最常见的自身免疫疾病,其典型临床表现为甲状腺毒症、甲状腺肿和眼病。GD的发病机制主要是甲状腺组织中淋巴细胞浸润导致产生促甲状腺激素受体(TSHR)抗体(TSAb),进而增加甲状腺激素的合成和释放并诱发其肥大。microRNAs(miRNAs)是一类长度约为22个核苷酸的非编码RNA,在真核生物的基因调控中发挥重要作用。miRNAs的形成过程十分复杂,主要由初级转录本进行一系列的处理,最终产生单链成熟的miRNAs。越来越多的证据表明,一些miRNAs在调节GD发生发展中扮演重要角色,并且血清中异常表达的某些miRNAs有助于GD的诊断。回顾miRNAs的生物发生过程,概括GD中miRNAs的表达变化,并系统阐述miRNAs在GD中的诊断价值、生物学作用及调控机制的相关进展。     

作为新型肿瘤标志物的分泌性miRNAs

MicroRNAs（miRNAs）是一类能够降解或抑制靶mRNA转录后水平的一类非编码小RNA.许多研究表明,在肿瘤的发生、转移等方面都与miRNA的调节异常有关.最近的研究表明在血液或其他体液中分泌性miRNA的表达水平与癌症的发展、治疗反应和患者的存活相关.因此miRNAs很可能成为一种新型非侵入性癌症标记物的检测指标.本文总结了分泌性miRNAs在不同类型肿瘤的研究现状,并进一步展示了miRNA作为癌症标记物在临床检测中的进展.     

黑皮质素-4受体在神经病理性疼痛中的作用

背景 黑皮质素系统在调节能量平衡、食物摄取、心血管功能和性功能中起重要作用,近年来发现其在神经病理性疼痛中也发挥着重要作用,尤其是黑皮质素-4受体（melanocortin receptor 4,MC4R）. 目的 阐明MC4R在神经病理性疼痛发生发展中的作用及机制,为寻找神经病理性疼痛的新靶点提供思路。 内容 MC4R与阿片受体、P38有丝分裂原活化蛋白激酶（mitogen-activated protein kinase,MAPK）、神经肽Y（neuropeptide tyrosine Y,NPY）、降钙素基因肽（calcitonin gene-related protein,CGRP）等相互作用,参与神经病理性疼痛的产生和维持。主要综述近几年来MC4R在神经病理性疼痛中的研究进展。趋向 黑皮质素受体很可能是潜在的治疗神经病理性疼痛的新靶点。     

Opioid responsiveness

Cancer pain generally responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment. A small proportion of patients, of the order of 20%, have pain that does not respond well to conventional analgesic management. Because opioid analgesics are the most important part of this pharmacological approach, a terminology has developed which centres around whether or not pain will respond to opioid analgesics. The terms opioid-responsive-pain and opioid-non-responsive pain, or opioid-resistant-pain, have been used to differentiate between patients whose pain falls into these two broad groups. This terminology is not satisfactory because it implies an all or none phenomenon, that is that pain either does or does not respond to opioid analgesics. Rarely is there such a clear distinction in practice. This is because the end point when titrating dose against pain with strong opioid analgesics is not simply pain relief or lack of relief: adverse effects may limit dose titration. It is preferable to describe patients with pain which is relatively less sensitive to opioids and/or patients where there is an inbalance between analgesia and unwanted effects as having “opioid-poorly-responsive pain”. A pragmatic definition of opioid-poorly-responsive pain is pain that is inadequately relieved by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them. Included in this definition is so called paradoxical pain which is not a distinct entity. Neuropathic pain is the most common form of opioid-poorly-responsive pain. The underlying pathophysiology remains unclear but abnormal metabolism of morphine is not the cause of a poor response to this drug. Patients with opioid-poorly-responsive-pain should be considered for treatment with the same opioid by an alternative (spinal) route or with an alternative opioid agonist administered by the same route (whether oral or parenteral), in conjunction with adjuvant analgesics such as tricyclic antidepressants. The most commonly used alternative oral opioids are phenazocine and methadone; transdermal fentanyl is an additional option.     

Rhetoric and reality on acute pain services in the UK: a national postal questionnaire survey

Background. The study aimed to explore the extent to which NHSacute pain services (APSs) have been established in accordancewith national guidance, and to assess the degree to which cliniciansin acute pain management believe that these services are fulfillingtheir role. Methods. A postal questionnaire survey addressed to the headof the acute pain service was sent to 403 National Health Servicehospitals each carrying out more than 1000 operative proceduresa year. Results. Completed questionnaires were received from 81% (325)of the hospitals, of which 83% (270) had an established acutepain service. Most of these (86%) described their service asMonday–Friday with a reduced service at other times; only5% described their service as covering 24 hours, 7 days a week.In the majority of hospitals (68%), the on-call anaesthetistwas the sole provider of out of hours services. Services werecategorized by respondents as thriving (30%), struggling tomanage (52%) or non-existent (17%). There was widespread agreement(     

Paediatric chronic pain

Many children and adolescents experience chronic pain at some point in their childhood. While the majority may be successfully supported by their local services, some may develop persistent pain-related functional disability that should prompt referral to a multidisciplinary paediatric pain service for assessment. These teams work with the family to provide a framework for promoting rehabilitation and restoration of function based on the biopsychosocial model. Mental health difficulties including psychological trauma are often a significant factor. Individualized therapeutic work is core to the pain management pathway. Medications and therapeutic injections are used less frequently in children compared to adult practice but may have a role in facilitating rehabilitation as part of a multidisciplinary approach.     

Medicines optimization in acute and chronic pain

Pain is a complex condition and warrants a multidisciplinary approach based on a bio-psycho-social model. Whilst often successful in acute pain, pharmacological treatment is rarely successful on its own in the management of chronic pain due to the high number of patients needed to treat to achieve a clinically meaningful improvement in function, quality of life and pain scores. There are also significant side effects in the short and long term. Recent re-analysis of clinic trial data focused on individual responder rates, showed that there is a cohort of patients who achieve 50% pain relief with subsequent improvement in physical function. To avoid intolerable side effects from medication used for chronic pain, titration needs to be slow and aimed towards the agreed risk–benefit between patients and treating physician with a clear plan for weaning and cessation if these goals are not achieved. Pain-orientated physiotherapy, either on its own or as part of a pain management programme, should be offered and medication reduced or weaned after restoration of function has been achieved.     

The post-operative painful knee—Clinical and societal causation

Persistent post-surgical pain (PPSP) remains a problem after knee replacement. “Pain” is not likely to be monolithic or a single entity. It can broadly be divided into mechanical pain that is not continuous and is influenced by movement and non-mechanical pain, which is continuous and is marginally affected by activity. If the cause of mechanical pain can be identified, corrective surgery may help.Non-mechanical pain can be subdivided into three groups as follows: sepsis, neuropathic, and perceived pain. The first two groups can be treated to some extent, but the perceived pain group that is very heterogeneous, remains a significant problem.     

Management of acute pain

Acute pain is a common feature in the presentation of surgical and traumatic pathology and in postoperative patients. In pathological presentations acute pain may have a protective role serving as a warning sign, with muscle spasm helping to limit movement and prevent further injury. Acute postoperative pain can hinder recovery due to limited mobility and may lead to a range of complications, increasing patient morbidity and mortality. Timely and effective management of acute pain is therefore imperative. An acute pain service (APS) is able to assist in the management of complex patients and those with specific invasive analgesic interventions. However, the immediate prescribing is the responsibility of the admitting surgical doctor and therefore this article aims to give an overview of the considerations needed to ensure safe and effective management of acute pain.