外周阿片类药镇痛的研究进展

外周感觉神经的阿片受体受炎症的调控。位于炎性组织范围内的免疫细胞表达阿片肽,与感觉神经上的阿片受体结合,通过抑制这些神经的兴奋性和（或）炎症前神经肽的释放而产生镇痛作用。现简要介绍外周阿片类药镇痛,并探讨其与临床药理学的联系。在临床药理学的研究中,我们要充分应用外周阿片类药镇痛,克服它的局限性,以此推动外周阿片类药应用在临床镇痛的发展。     

椎管内非阿片类药物镇痛研究进展

随着人们对脊髓,特别是脊髓背角结构功能的认识和疼痛机制研究的深入,脊髓水平用药改变机体对痛觉的感知已引起科学家的广泛兴趣。不仅椎管内注入阿片类药物能够改变伤害性感受的传入,一些作用于其它分子靶标的药物应用于椎管内也能产生镇痛作用或增强阿片类药物镇痛并抑制其所致的耐受和依赖。现就椎管内非阿片类药物镇痛研究进展进行综述。     

术后硬膜外阿片类药物镇痛的研究进展

对近期硬膜外阿片类药物术后镇痛相关文献进行了回顾,表明:持续输注亲水性阿片可产生选择性脊髓镇痛作用,而副作用发生率低;亲脂性阿片药镇痛的产生可能脊髓作用有关,但单独硬膜外给药与静脉内镇痛相比并无明显优势;联合使用小剂量脂溶性阿片和局麻药比全身性单独注射阿片可能具有明显的临床优势;还需进一步研究剂量范围以取得镇痛最佳、副作用发生率最低的临床效果。     

P-糖蛋白与阿片类药物镇痛的研究进展

P-糖蛋白(P-gp)是多药耐药基因编码的一种依赖ATP、能外排异物的跨膜蛋白,P-gp底物分为两大类:促进剂和抑制剂。促进剂如吗啡,可诱导P-gp表达。本文主要介绍血-脑脊液屏障上的P-gp在中枢神经系统中对阿片类药物生物利用度所起的作用,P-gp抑制剂与阿片类药物镇痛的关系及其研究进展。     

P-糖蛋白与阿片类药物镇痛的研究进展

P-糖蛋白(P-gp)是多药耐药基因编码的一种依赖ATP、能外排异物的跨膜蛋白，P-gp底物分为两大类：促进剂和抑制剂，促进剂如吗啡，可诱导P-gp表达。本文主要介绍血-脑脊液屏障上的P-gp在中枢神经系统中对阿片类药物生物利用度所起的作用，P-gp抑制剂与阿片类药物镇痛的关系及其研究进展。     

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。     

阿片类药物依赖性机制研究进展

阿片类药物依赖性的形成涉及复杂的生物学机制。在受体水平,主要涉及μ受体;受体后机制则主要体现在腺苷酸环化酶活性、离子通道和基因转录的改变。另外,多种神经递质如多巴胺、氨基酸和内源性阿片肽,以及突触可塑性变化如LTP等也参与了阿片类药物依赖性的形成。     

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。     

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。阿片类药物外周镇痛的临床研究正在进行。     

ICU镇痛与阿片类药物应用的利与弊

国际疼痛研究学会将疼痛定义为：与急性组织损伤或潜在组织损伤或类似损伤相关的不愉快的感觉和情感体验［1］。最新的研究表明,在内科和外科ICU的患者中,有超过50％的患者经受着疼痛的折磨,70％以上的患者在ICU期间存在着焦虑与躁动［2］。因此,对于IUC患者镇痛治疗是十分必要的。     

阿片类药预处理对心脏的保护作用

Murry于1986年首次描述了缺血预处理(ischem icpreconditioning)现象,即短暂的心肌缺血后能使心脏耐受更长时间的缺血刺激。分早期保护作用,发生于缺血刺激后1 h~3 h,延迟保护作用,发生于缺血刺激后12 h~72 h。后来在临床上也发现了缺血预处理的证据。心梗前短期内曾发生心绞痛     

Intra-articular morphine for pain relief after knee arthroscopy

BACKGROUND: Peripheral opioid analgesia is well documented. But the clinical usefulness of intra-articular morphine after surgery is uncertain. The aim of the present study was to evaluate the analgesic effects of intra-articular morphine after knee arthroscopy. METHODS: In this parallel-group, double-blind study, 90 patients were randomised to receive either morphine 1 mg, morphine 2 mg or placebo in 5 ml saline intra-articularly at the end of arthroscopic knee surgery. Anaesthetic technique was local infiltration and intra-articular injection of lidocaine. Analgesic efficacy was evaluated by a global pain score, pain intensity (visual analogue scale), and analgesic requirements (paracetamol) during the first 48 h postoperatively. RESULTS: No significant differences between the groups were found for any of the efficacy variables. A majority of the patients had mild pain throughout the study, thus possibly compromising study sensitivity. In a subgroup with more intense pain early after arthroscopy, intra-articular morphine 2 mg reduced pain intensity (P < 0.05) and analgesic requirements (P < 0.05) compared with placebo. CONCLUSION: Postoperative analgesic effect of intra-articular morphine was found only in a subgroup of patients with higher pain intensity in the immediate postanaesthetic period. Possible reasons for our overall negative findings include low study sensitivity due to weak pain stimulus, lack of inflammation that may be a prerequisite for peripheral opioid analgesia, and the local anaesthetic, which impedes local inflammatory reaction and expression of peripheral opioid receptors. These factors may also explain the conflicting results in other studies.     

阿片类药物延迟预处理心肌保护作用的研究进展

与缺血预处理类似,阿片类药物预处理亦可诱发延迟性心肌保护作用,临床应用麻醉性镇痛药如吗啡等可通过激动阿片受体而减轻缺血/再灌注损伤.研究发现,阿片类药物预处理的延迟性心肌保护作用持续时间较长,所以对预防心肌缺血/再灌注损伤更具临床应用价值.此文综述了阿片类药物预处理延迟性心肌保护作用的生理学基础和机制.     

阿片受体的外周作用与心脏保护

阿片受体（opioidreceptors,OR）在镇痛、心血管调节等方面的作用已为大家所知,但以往研究多于中枢水平。近年来,OR的外周作用日益受到重视。越来越多证据表明OR在心脏病理生理过程中有重要意义。现就心脏OR保护性作用研究的进展作一综述。     

Opioid mechanisms and opioid drugs

The opioid system comprises four receptor subtypes: μ (MOP), κ (KOP), δ (DOP), now called the ‘classical’ opioid receptors, and the ‘non classical’ nociceptin/orphanin FQ peptide (N/OFQ) receptor (NOP). Selective endogenous peptides, cleaved from larger precursor proteins, have been identified for all subtypes. Both classical and non-classical opioid receptors couple to inhibitory, pertussis toxin-sensitive G-proteins. Opioid receptors activate the same major intracellular pathways, which include: closing of voltage-sensitive calcium channels; opening of potassium channels and subsequent cellular hyperpolarization; and inhibition of cyclic adenosine monophosphate (cAMP) production through inhibition of the enzyme adenylate cyclase. All current, clinically used opioids work through activation of the MOP receptor. In an experimental setting, co-administration of MOP and DOP agonists has been shown to have a synergistic analgesic action. Administration of DOP-receptor antagonists has also been shown to reduce tolerance, physical dependence and other side effects of MOP-receptor agonists, without detriment to their analgesic action. In animal models NOP agonists are analgesic when administered spinally and have a pronociceptive/anti-analgesic (or anti-opioid) effect supraspinally. NOP knockout mice show a partial loss of tolerance to morphine and there is an up-regulation of N/OFQ production in chronic morphine tolerant mice. Analgesic tolerance that develops from repeated exposure to morphine is markedly attenuated in NOP knockout mice. The development of ligands with mixed action at MOP, DOP and NOP receptors offer new opportunities for opioid pharmacology.     

复合镇痛方剂用于脊柱后路手术术后镇痛的临床疗效观察

[目的]观察复合镇痛方剂用于脊柱后路胸腰椎内固定手术病人术后镇痛的临床疗效.[方法]选择行后路脊柱胸腰椎内固定手术患者60例,双盲法随机分为A、B两组:A组为观察组,在病人术毕缝合皮肤前给予复合镇痛方剂(吗啡+肾上腺素+罗哌卡因+生理盐水)椎旁肌肌注,B组为对照组,不予肌注.记录术后4、8、12、24、36、48 h病人刀口疼痛VAS评分、镇静评分、不良反应(皮肤瘙痒、头晕、恶心、呕吐、呼吸抑制)发生情况及术后补救镇痛情况,调查患者满意率.[结果]观察组术后4、8、12、24、36、48 h刀口疼痛评分显著降低,镇静评分升高,且手术12h后差异更明显,与对照组相比两组间差异有显著统计学意义(P＜0.01),术后患者整体镇痛满意度明显提高(P＜0.05),而有关不良反应发生率的差异无统计学意义(P＞0.05),观察组与对照组相比能明显降低术后疼痛评分,减少术后补救镇痛次数.[结论]该复合镇痛方剂用于脊柱后路胸腰椎手术术后镇痛可取得良好的镇痛、镇静效果,不良反应少,安全性高,值得临床推广.     

Choice of opioid for initiation of combined spinal epidural analgesia in labour--fentanyl or diamorphine

Sixty-two women requesting regional analgesia in labour wereallocated to receive a 1.5 ml intrathecal injection aspart of a combined spinal–epidural (CSE) analgesic technique.This contained either bupivacaine 2.5 mg plus fentanyl25 µg (group F) or bupivacaine 2.5 mg plus diamorphine250 µg (group D). Times of analgesic onset and offsetwere recorded, motor and proprioceptive assessments made andside-effects noted. Analgesic onset was not significantly differentbetween the groups (group F, 8.0 min; group D, 9.5 min; P=0.3)but time to first top-up request was significantly longer inthe diamorphine group (group F, 73 min; group D, 101 min; P=0.003).Motor loss, assessed by the modified Bromage score, was statisticallybut not clinically greater in the fentanyl group (P=0.01). Maternalhypotension, pruritis, proprioceptive loss, nausea and fetalbradycardia were rare and not severe, and their incidences didnot differ between groups. No respiratory depression was observedafter CSE. This use of diamorphine was not associated with increasedside-effects compared with fentanyl/bupivacaine, and it hasa longer duration of action. Br J Anaesth 2001; 86: 567–9