阿片类药物与基因多态性

由于在缓解中、重度疼痛方面的强效作用,所以阿片类药物在临床上被广泛用于辅助外科手术麻醉和手术后疼痛治疗.已经证实,阿片类药物的镇痛作用在不同人群和个体之间具有明显的变异.基因多态性可通过影响阿片转运蛋白、靶受体和代谢酶的表达而导致该现象的发生.现就基因多态性对阿片类物镇痛作用的影响作一综述.     

雌激素在阿片类药物镇痛中的作用

有关雌激素在阿片类药物中作用的研究越来越受到重视．它既可以通过影晌阿片药物的药效动力学和药代动力学来调节阿片镇痛的效果,也可以通过影响不同部位的阿片受体的基因和蛋白表达来影响阿片药物的镇痛效果。本文在回顾以往文献的基础上,对雌激素在阿片类药物镇痛中的作用机制作一综述。     

阿片类药物诱发痛觉过敏的药物干预

摘要应用阿片类药物进行镇痛时可能诱发痛觉过敏,此时增加阿片类药物的剂量不仅不能加强其镇痛效果,反而可能导致疼痛加剧,在这种情况下需应用其他的镇痛药物进行干预。该文总结可用于阿片类药物诱发痛觉过敏的药物及其作用机制,为临床医生选择镇痛药物提供参考。     

椎管内镇痛药之间的相互作用

临床和实验研究发现椎管内应用阿片类药物和局麻药、α_2-受体兴奋药之间;阿片类药物之间;阿片类药物和其它药物之间存在协同和叠加作用。临床椎管内应用阿片类药于慢性疼痛治疗应发挥药物的协同镇痛作用,减少毒、副作用的产生。     

阿片类药物的性别特异性反应：动物及人类研究

已有大量的研究报道显示，作用于μ、κ、和δ阿片受体的麻醉性镇痛药物对男性和女性的作用存在质和量的差异。这种性别相关的差异并不局限于阿片类药物的镇痛／抗伤害性感受的作用上，也表现在阿片类药物介导的副作用方面，如对呼吸、运动、学习（记忆）的影响、药物成瘾性以及心血管系统的变化等。越来越多的对照性动物和人类研究直接探讨了阿片类药物作用效能在性别方面的区别；结果显示，尽管性别可能影响阿片类药物的镇痛作用，但是这种性别差异的方向和大小取决于许多因素的相互影响。这些因素包括药物本身的一些特性，以及研究个体的一些特征，前者如药物剂量、药理学、给药途径与时间，后者包括实验动物的品系、疼痛的类型、遗传学差异、年龄、性腺／激素分泌的状态。本文系统地介绍了这些动物和人类研究的结果，并分析与各种因素相关的数据。尽管观察到的阿片类药物作用的性别差异可能与临床相关，但是对引起阿片类镇痛药物敏感性巨大个体差异的其他因素缺乏了解，迫使临床医师要根据患者个体需求来制定个体化给药方案。     

椎管内镇痛药之间的相互作用

临床和实验研究发现椎管内应用阿片类药物和局麻药、α２－受体兴奋药之间，阿片药物之间；阿片类药物和其它药物之间存在协同和叠珈作用。临床椎管内应用阿片类药于慢性疼痛治疗发挥药物的协同镇痛作用，减少毒、副作用的产生。     

阿片类药物外周镇痛的研究进展

当前治疗各种急、慢性疼痛的所用药物中,阿片类制剂仍然扮演了极为重要的角色,随之而来的是全身用药产生的副作用,如呕吐、呼吸抑制、成瘾等,限制了阿片类药物的应用,外周局部小剂量的应用阿片类药物可产生有效的外周镇痛,从而为临床上控制疼痛提供了一条新的途径.     

阿片类药物依赖患者的术后镇痛

背景 阿片类药物是术后镇痛的主要药物,但长期使用阿片类药物的患者因对阿片类药物产生耐受而难以得到较理想的临床术后镇痛效果.目的 讨论如何采用不同的镇痛技术和药物来更好地为这些患者提供良好镇痛.内容 介绍阿片类药物依赖的流行病学及术后镇痛特点,如何对阿片类药物依赖规范合理使用阿片类药物及辅助类镇痛药物,麻醉医生擅长的神经阻滞技术在该类患者应有独特的地位.趋向 在阿片类药物依赖患者,通过使用阿片类药物、局麻药和辅助性镇痛药,将不同作用机制的药物或方法联合使用,发挥药物的相加或协同作用的平衡镇痛及多模式镇痛将是术后镇痛技术的主要发展方向.     

阿片类药物的外周镇痛作用

阿片类药物的外周抗伤害和镇痛是通过外周阿片受体起作用。初级感觉神经元内存在着阿片受体，在炎症的条件下，阿片受体合成增加并转运到神经末梢，增强阿片类物质的外周作用。炎症部位的免疫细胞释放多种内源性阿片肽，作用于外周阿片受体产生抗伤害和镇痛作用。阿片肽代谢酶抑制剂也能增强阿片肽的外周作用。阿片类芗外周镇痛的临床研究正在进行。     

低阿片多模式镇痛在老年髋部骨折围手术期的应用进展

老年髋部骨折围术期会产生剧烈的疼痛,造成多种不良事件的发生。因此,有效的镇痛对老年髋部骨折患者至关重要。低阿片多模式镇痛指应用多种作用机制不同靶点不同的镇痛药物或镇痛方法,使其发挥协同作用,最大程度缓解疼痛,减少有害刺激传入中枢降低疼痛发生,同时在保证镇痛的前提下,达到阿片类药物的用量最小化,降低阿片药物相关不良反应。近年来,低阿片多模式镇痛理念在老年髋部骨折手术中的应用愈加广泛。本文就低阿片多模式镇痛在老年髋部骨折手术应用状况做一综述,以期指导未来的临床应用和研究。     

疼痛敏感性及阿片类镇痛药用量与多巴胺转运体基因多态性的相关性

目的探讨多巴胺转运体(dopamine transporter, DAT)基因(DAT1)多态性对疼痛敏感性及阿片类镇痛药用量的影响。方法选择择期上腹部手术的汉族患者121例,抽取患者外周静脉血通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测DAT1可变串联重复(VNTR)多态性,利用便携式压力测试仪对患者试验性疼痛压力痛阈(PPT)和压力耐痛阈(PTO)进行检测,记录患者术后阿片类镇痛药用量,分析患者的生物社会学特征和DAT1 VNTR多态性与疼痛敏感性和术后阿片类镇痛药用量的关系。结果 121例患者中,DAT1 VNTR等位基因的分布频率分别为9R(18.2%)、10R(81.8%),基因型分布频率分别为9R/9R(7.4%)、9R/10R(21.5%)、10R/10R(71.1%)。不同DAT1 VNTR等位基因型患者PPT和PTO差异无统计学意义,术后24 h和48 h阿片类药物用量差异无统计学意义。不同DAT1 VNTR等位基因型患者中,40岁以下患者的PTO明显高于65岁以上的患者(P0.05),阿片类镇痛药用量明显多于65岁以上患者(P0.05)。结论 DAT1 VNTR多态性可能与疼痛敏感性及术后阿片类镇痛药用量无关。     

Remarks on some analgesics used in the pain clinic

The mechanism of action of aspirin as an analgesic is an inhibition of biosynthesis of prostaglandins. Thus the site of action has been believed to be peripheral. However, when aspirin is injected intra- thecally, it produces an analgesic effect. Aspirin has a membrane-stabilizing effect and it is used locally for the treatment of post- herpetic neuralgia. Epidural opioids are frequently used for the management of post-operative pain or cancer pain. Pharmacokinetic studies have shown that delayed respiratory depression results from migration of morphine in the cerebrospinal fluid to the brain. Peak concentrations of morphine near the brain stem occur about 3 hours after lumbar epidural injection, whereas lipophilic opioids such as meperidine, peak concentration occur within 30 to 60 minutes. The clearance from cerebrospinal fluid of lipophilic opioids is more rapid than that of morphine. Besides opioids, alpha 2 receptor agonists such as clonidine also have analgesic action when administered into the epidural space. Somatostatin is one of many neuropeptides found in the spinal cord. It has dual action: a mediation of thermal nociception and a general antinociceptive action. When somatostatin is administered intrathecally or epidurally, it produces analgesic effect and its efficacy appears to be equal to that of morphine.     

过氧亚硝酸阴离子引起阿片耐受或痛觉过敏的研究进展

背景 吗啡等阿片类药物是临床疼痛治疗的代表性药物,主要用于急、慢性疼痛和癌痛的治疗,但长期应用可产生诸多副作用,如吗啡耐受和痛觉过敏等,从而大大限制了阿片类药物在临床上的使用. 目的 通过对近年过氧亚硝基阴离子在吗啡耐受和痛觉过敏中所起作用的研究进行总结,帮助读者了解国外相关研究的最新趋势和进展. 内容 就过氧亚硝基阴离子的生成途径、消除方式和过氧亚硝基阴离子在阿片耐受或痛觉过敏中的作用方式进行综述.得出如下结论,过氧亚硝基阴离子主要通过硝基化体内蛋白质酪氨酸残基、激活神经炎症和促进细胞凋亡3个方面,引起阿片耐受或痛觉过敏. 趋向 随着越来越多的学者对过氧亚硝基阴离子在吗啡耐受和痛觉过敏中发挥的重要作用达成共识,过氧亚硝基阴离子有望成为临床疼痛治疗的新靶点.     

Pain management after major orthopaedic surgery: current strategies and new concepts

Several recently developed analgesic techniques effectively control pain after major orthopaedic surgery. Neuraxial analgesia provided by epidural and spinal administration of local anesthetics and opioids provides the highest level of pain control; however, such therapy is highly invasive and labor intensive. Neuraxial analgesia is contraindicated in patients receiving low-molecular-weight heparin. Continuous plexus and peripheral neural blockades offer excellent analgesia without the side effects associated with neuraxial and parenteral opioids. Intravenous patient-controlled analgesia allows patients to titrate analgesics in amounts proportional to perceived pain stimulus and provide improved analgesic uniformity. Oral sustained-release opioids offer superior pain control and greater convenience than short-duration agents provide. Opioid dose requirements may be reduced by coadministration of COX-2-type nonsteroidal analgesics.     

Transdermal buprenorphine for treating nociceptive and neuropathic pain: four case studies

The use of opioids for treating neuropathic pain is controversial, and some studies have indicated that neuropathic pain may be relatively insensitive to typical mu-opioid analgesics such as morphine. However, it is becoming clear that different opioids produce analgesia by affecting different pain pathways. We present two cases of neuropathic pain and two cases of nociceptive pain with a significant neuropathic component that were treated with transdermal buprenorphine. In each case, sufficient pain relief was obtained and no problems were encountered in switching from prior analgesic therapy with larger doses of other opioids.     

Challenges in the Optimisation of Post-operative Pain Management with Opioids in Obese Patients: a Literature Review

An increasing number of obese patients are undergoing surgery, particularly bariatric and orthopaedic surgery. The physiological differences between obese and normal-weight subjects may modify not only anaesthetic requirements during surgery but also post-operative analgesic management, raising a number of challenges in a critical period. In this review, we analyse studies of post-operative pain management with opioids in obese subjects. We discuss the genetic factors common to pain and obesity and the factors potentially modifying opioid pharmacokinetics and pharmacodynamics in obese patients, and we analyse the overall efficacy and safety of opioids for pain management during the post-operative period in obese patients. Both modifications to surgical methods and additional analgesic treatments to decrease the requirement for opioids may improve early rehabilitation and quality of care and reduce adverse effects in obese patients.     

Peripheral opioid analgesia: from experimental to clinical studies

Previous experimental findings demonstrating that the local administration of opioids produces dose-dependent and naloxone-reversible analgesic effects, which are restricted to the periphery, have now been confirmed in clinical studies. Accordingly, opioid receptors have been identified on peripheral sensory neurons of animals and humans. In addition to their efficacy in somatic pain, peripheral opioids potently inhibit visceral pain. These effects are enhanced under inflammatory conditions. Initial clinical trials have now examined local opioid effects in chronic inflammatory states such as arthritis. They demonstrated surprisingly long-lasting analgesic effects, probably caused by additional anti-inflammatory effects. The introduction of a new generation of opioids that act selectively in the periphery may open a novel approach to treating pain effectively without undesirable central side-effects such as respiratory depression and addiction.     

Weak opioids--an educational substitute for morphine?

The World Health Organization guidelines suggest the use of weak opioids on the second step of the analgesic ladder for cancer pain relief. Weak opioids are important substitutes for low doses of morphine, although their analgesic efficacy is lower than that of non-opioid or strong opioid analgesics. The use of weak opioids has great educational impact and has helped spread the use of the guidelines. Furthermore, weak opioids are more freely available and are expected to have a better side-effect profile. Controlled long-term studies are required for confirmation.     

Opioid therapy in chronic non-malignant pain

In long-term treatment opioids seem to have only minimal side-effects compared with other analgesics and co-analgesics.Nevertheless, some risks have to be considered. While immunosuppression, neurotoxicity, teratogenity, tolerance and addiction are clinically not relevant or very rare, cognitive impairment, sedation and obstipation may have a clinical impact.However, these symptoms can usually be managed by adjuvant medication and patient education.Treatment of non-malignant pain with opioids can only be considered on an individual basis. Scientific evidence for general treatment with opioids, treatment of specific pain syndromes or treatment with certain opioids is not available. In conclusion, only recommendations regarding opioid treatment for certain chronic pain syndromes can be made. In only a minority of patients can a long-term analgesic effect be expected.Therefore, careful evaluation of alternative options of pain management is necessary before opioid therapy is started.With standardized documentation responders may be distinguished from non-responders.For clinical practice of long-term opioid therapy in non-malignant pain a specialized knowledge in pain management is a prerequisite.Future studies with more sophisticated methodology will be necessary to advocate more precise guidelines.However, the therapeutic recommendations from the DGSS consensus conference allow a safer,well structured and validated use of opioids for chronic non-malignant pain.