氟哌啶醇与吗啡协同镇痛作用机制分析

目的 研究氟哌啶醇与吗啡协同镇痛作用的机制。方法 热板法。结果 氟哌啶醇与阈下剂量的吗啡配伍注射可显著提高小鼠的痛阈。纳洛酮和苯丙胺均可降低氟哌啶醇与吗啡配伍使用后小鼠的痛阈。结论 氟哌啶醇与吗啡的协同镇痛作用中,吗啡可能起主导作用,而多巴胺能神经的活动仅起到调节作用。     

氟哌啶醇协同阈下剂量哌替啶镇痛作用的研究

目的 观察阈下剂量哌替啶对氟哌啶醇合用后对镇痛作用的影响。方法 热板法。结果 氟哌啶醇与阈下剂量哌替啶配伍注射可显著提高小鼠痛阈。结论 氟哌啶醇与哌替啶合用后可产生明显协同镇痛作用。     

氟哌啶醇与阈下镇痛剂量强痛定协同镇痛作用实验研究

目的：研究氟哌啶醇与阈下镇痛剂量强痛定协同镇痛作用。方法：参照药理实验方法学热板法,以小鼠放置热板至舔后足时间做为痛阈。结果：阈下镇痛剂量的强痛定与氟哌啶醇叠加后,镇痛作用显著增强,并有良好时效关系。结论：氟哌啶醇与强痛定之间具协同的抗痛作用。     

氟哌啶醇与吗啡合用对醋酸导致小鼠扭体反应的影响

目的 观测阈下镇痛剂量的吗啡与氟哌啶醇合用后对醋酸导致小鼠扭体反应的抑制作用。方法 小鼠腹腔注射（ip)药物20min后,再ip0.7%醋酸致痛,记录注射醋酸后小鼠出现扭体的时间和20min内的扭体次数。结果 阈下镇痛剂量的吗啡（1．25mg/kg）与氟哌啶醇（0．625mg/kg)合用后,显著地抑制醋酸导致小鼠扭体次数和延长扭体出现的潜伏期。结论 氟哌啶醇与吗啡合用后可产生明显的协同镇痛作用。     

氟哌啶醇与阈下剂量吗啡合用对小鼠成瘾性的研究

目的：观察氟哌啶醇与阈下剂量吗啡合用对小鼠成瘾性的影响。方法：自然戒断试验。结果：吗啡与氟哌啶醇配伍组元一发生竖尾和自发惊厥。结论：吗啡与氟哌啶醇合用,在产生明显协同镇痛作用的同时,致成瘾性却比等效剂量吗啡低得多。     

脑室注射r-氨基丁酸(GABA)对大鼠垂体-甲状腺分泌功能的抑制效应

脑室注射10μl含8molGABA的人工脑脊液后60min,大鼠血清TSH、T4、T3含量与注射人工脑脊液的对照组比显著降低(P<0.001、0.01、0.05);若在注射GABA前1min,预先注射10μl多巴胺受体阻断剂氟哌啶醇(5g/1)、10μl肾上腺素受体阻断剂酚妥拉明(10g/1)或10μlGABA受体阻断剂青霉素(3.35×10~(-2)mol/l),可以阻断GABA对TSH、T4、T3分泌的抑制效应.结果证明脑中GABA能系统参与垂体-甲状腺功能的调制,提示GABA通过多巴胺能和肾上腺素能神经元,抑制下丘脑分泌TRH,从而影响垂体分泌TSH,最终抑制了甲状腺的分泌功能.     

大鼠侧脑室注射云芝糖肽的镇痛试验

本文以Ｋ＋透入法测定大鼠的甩尾阈，观察侧脑室注射云芝糖肽对大鼠甩尾阈的影响并与腹腔注射云芝糖肽的作用比较．实验结果表明侧脑室注射４００μｇ或２００μｇ云芝糖肽都能极显著地提高大鼠的甩尾阈，量效关系显著．侧脑室注射１０μｇ吗啡的镇痛作用显著高于２００μｇ云芝糖肽的作用，但与４００μｇ云芝糖肽的作用相近．腹腔注射１００ｍｇ／ｋｇ云芝糖肽也能极显著地提高大鼠的甩尾阈，但其镇痛作用远较侧脑室注射４００μｇ云芝糖肽和腹腔注射４ｍｇ／ｋｇ吗啡的作用弱．     

首乌制剂对MPTP引起的小鼠帕金森病的防治

实验选用成年ICR纯系小鼠，通过对小鼠主动运动以及脑内多巴胺（DA）含量的测定，观察首乌的醇提取物对MPTP引起的小鼠帕金森病的预防与治疗作用。实验发现，注射MPTP后，小鼠主动性活动明显减少，脑内DA含量明显降低，表现出帕金森病的特征。对这些小鼠再注射首乌制剂能促进小鼠的运动，脑内DA的含量得以恢复。若同时注射MPTP和首乌制剂，则小鼠主动性活动时间以及纹状体多巴胺的含量都明显高于单独注射MPTP组。实验提示，MPTP可引起ICR小鼠脑内多巴胺神经元损伤并产生帕金森病症状，而首乌制剂对MPTP的毒性作用有明显的预防作用和一定的治疗作用，这可能与首乌制剂抑制型单腔氧化酶的活性有关。     

辣椒总碱对实验动物的镇痛效果研究

目的:探讨辣椒总碱的镇痛作用。方法:观察辣椒总碱溶液对醋酸引起的小鼠扭体反应次数的影响,对小鼠痛阈的影响(热板法),对大鼠痛阈的影响(甩尾法);辣椒总碱软膏对大鼠痛阈的影响(福尔马林炎症痛模型)。结果:辣椒总碱溶液(0.01%、0.03%、0.05%)能显著降低小鼠扭体次数,能显著提高小鼠和大鼠的痛阈值;辣椒总碱软膏(0.09%)能显著提高大鼠的痛阈值。结论:辣椒总碱对小鼠和大鼠具有显著的镇痛作用。     

下丘脑—垂体—肾上腺皮质系统在针刺镇痛中的作用(Ⅱ) 环—磷酸腺苷(CAMP)及三磷酸腺苷(ATP)对大白鼠垂体——肾上腺皮质系统及针刺镇痛效应的影响

大量临床实践及动物实验表明,机能调整可能是针刺镇痛的基础。即在针刺作用下,机体内发生一种生理范畴的积极主动的调整过程,通过神经——体液系统,改变机体的原有机能状态,使之达到新的统一,从而影响痛阈,起到针刺镇痛效果。针刺作用下肾上腺皮质机能亢进及其与针刺镇痛的关系,已有不少报导。我们用脑内激素埋藏技术,在大白鼠下丘脑腹内侧核埋藏氢化可的松,可以阻断下丘脑——垂体——肾上腺皮质系统,并发现这样的大白鼠动物模型,其针刺镇痛效应下降。为了进一步探讨这一系统在针刺镇痛中的作用,能否激活这一系统,同时观察动物痛阈及针刺镇痛效应的变化,不仅有助于从理论上阐明垂体——肾上腺皮质系统与针刺镇痛的关系,而且从临床实践角度来看,通过机能调整探索克服针麻存在问题的有效途径,也将是有意义的。激素作用的第二信使环一磷酸腺苷(CAMP)与三磷酸腺苷(ATP)合用可以激活下丘脑——垂体——肾上腺皮质系统。因此,我们应用这一方法希望激活大白鼠这一系统时,观察动物痛阈、肾上腺抗坏血酸及针刺镇痛效应等的变化,以便进一步了解这一系统与针麻效应的关系。     

A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser.

It is generally accepted that morphine exerts its analgesic effect by binding to specific opiate receptors in the brain and spinal cord. Since Hughes et al. isolated and identified two endogenous pentapeptides, Met- and Leu-enkephalin, from the brain and found that they acted as agonists at opiate receptors, alpha-, beta- and gamma-endorphins, larger peptides than enkephalins and having morphine-like activity, have been identified in either the brain or pituitary of various species. Several studies have demonstrated that enkephalins possess analgesic properties and that they are distributed in the pain-mediated pathways in the central nervous system. These findings suggest that enkephalins are important neurotransmitters or neuromodulators regulating pain transmission. We now report the isolation of a novel substance which has a Met-enkephalin releasing action. Our findings suggest the possibility of a regulating mechanism for the release of endogenous opioid peptides, especially Met-enkephalin.     

茴香霉素对镇痛耐受及脑线粒体钙的影响

本文研究了蛋白质合成抑制茴香霉素对吗啡、丁丙诺啡和电针耐受发展的影响,监用铽离子探针测定被处理动物不同脑区的线粒体一Ca~2+水平。结果表明,茴香霉素能抑制吗啡和电针的耐受,但不能抑制丁丙诺啡耐受发展。痛阈与下丘脑和导水管周固灰质区线粒体-Ca~(2+)水平有良好的平行关系。本文还对Tb~(3+)与线粒体上色氨酸和酪氨酸的结合及影响荧光测定的因素进行了探讨。     

Do human platelets have opiate receptors?

In their study of prostaglandin E1 (PGE1)-sensitive adenylate cyclase (AC) in rat brain homogenates, Collier and Roy claimed that the activity of this enzyme is inhibited by opiates. They also proposed that opiates exert their analgesic and allied effects by inhibiting AC of neurones that are normally stimulated by E prostaglandins. Studies using neuroblastoma x glioma hybrid cells supported this hypothesis. However, subsequent studies with mammalian brain and rat brain tissue slices yielded conflicting results. PGE1 also inhibits platelet aggregation, probably through activation of platelet AC. Gryglewski et al. showed that morphine inhibits the anti-aggregating effect of PGE1 on ADP- and adrenaline-induced platelet aggregation, and suggested that the inhibition by morphine is mediated through platelet AC activity. We report here our attempts to reproduce the results of Gryglewski et al. and our examination of the effect of morphine on PGE1-sensitive AC activity in platelet lysates and on PGE1-induced accumulation of cyclic AMP in intact platelets. The possible existence of opiate receptors in platelets was also assessed by direct binding studies with 3H-etorphine. In contrast to Gryglewski et al., we could not detect any effect of opiates on the aggregation of human platelets, nor did we find any other evidence supporting the presence of opiate receptors in these cells. Thus we conclude that the presence of opiate receptors in human platelets is unlikely.     

酮络酸复合芬太尼硬膜外术后镇痛的效应观察

酮络酸为新型强效非类固醇类镇痛抗炎药．本研究拟观察静注酮络酸加强芬太尼硬膜外术后镇痛的效应．结果显示：单纯静注酮络酸或硬膜外芬太尼均有较明显的术后镇痛作用，但仍需辅用较大剂量的哌替啶；而静注酮络酸和硬膜外芬太尼联合用药，则术后镇痛效果明显加强，镇痛持续时间显著延长，哌替啶的用量锐减，恶心、呕吐发生率降低，未出现呼吸抑制现象．本研究还证实酮络酸可加强芬太尼硬膜外术后镇痛的效果，减少其用量，减轻其副作用，为较理想的用药组合．     

Morphine reward in dopamine-deficient mice

Dopamine has been widely implicated as a mediator of many of the behavioural responses to drugs of abuse. To test the hypothesis that dopamine is an essential mediator of various opiate-induced responses, we administered morphine to mice unable to synthesize dopamine. We found that dopamine-deficient mice are unable to mount a normal locomotor response to morphine, but a small dopamine-independent increase in locomotion remains. Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia. In contrast, dopamine-deficient mice display a robust conditioned place preference for morphine when given either caffeine or l-dihydroxyphenylalanine (a dopamine precursor that restores dopamine throughout the brain) during the testing phases. Together, these data demonstrate that dopamine is a crucial component of morphine-induced locomotion, dopamine may contribute to morphine analgesia, but that dopamine is not required for morphine-induced reward as measured by conditioned place preference.     

Effect of nocistatin in pain modulation

Using tail-flick latency as the nociceptive index and von Frey hair to measure the mechanical allodynia, the aim of the present study is to determine whether nocistatin, injected intracerebroventricularly (i.c.v.), would reverse the anti-morphine effect of orphanin FQ (OFQ), and, injected i.c.v. or intrathecally (Lt.), would inhibit the mechanical allodynia in a L5 and L6 spinal nerve ligation model of neuropathic pain in rats. The results show that i.c.v. injection of nocistatin produces no significant changes in the TFL, nor does it affect morphine analgesia. In addition, i.c.v. or i.t. nocistatin produces no significant changes in withdrawal threshold of the nerve-lesioned hind paw. However, nocistatin significantly reverses the antagonistic effect of OFQ on morphine analgesia when it was coinjected i.c.v. with OFQ. The results suggest that nocistatin can reverse the anti-morphine effect of OFQ in rat brain, but cannot inhibit the mechanical allodynia of neuropathic pain in rat brain and spinal cord.     

金铃子散复方配伍的镇痛研究

为观察金铃子散及其各单味药对小鼠镇痛作用的影响,通过热板法和醋酸扭体法研究了金铃子散及其单味药的镇痛作用效果。结果表明：金铃子散复方及其单味药水煎液可使热板法小鼠在给药后30min,60min,90min及120min痛阈值明显延长,醋酸所致小鼠扭体次数明显减少（p＜0.05,p＜0.01）,其中金铃子散作用效果最为明显。可见金铃子散具有明显的镇痛作用,且镇痛效果优于单味药。     

乙酰水杨酸对福尔马林致痛大鼠的行为学影响

以往用细胞内微电极技术研究发现乙酰水杨酸可引起大鼠背根神经节神经元膜产生明显的超极化反应,即能产生外周神经镇痛作用。本实验旨在利用大鼠福尔马林致痛模型,通过观察大鼠的痛行为反应,建立乙酰水杨酸镇痛模型,以探索乙酰水杨酸可能的中枢及外周镇痛机制。将24只Wistar大鼠随机分为3组:生理盐水组、福尔马林致痛组和乙酰水杨酸镇痛组。结果发现,福尔马林致痛组大鼠的缩腿次数和舔爪时间都明显长于生理盐水组,给予乙酰水杨酸后,缩腿次数和舔爪时间均明显减少。故认为乙酰水杨酸可明显减轻福尔马林所致的痛行为反应。     

铁棒锤氯仿部位的毒-效关系研究

为探讨铁棒锤的毒效关系,提取分离其氯仿部位并采用HPLC分析其主成分,比较了该部位与铁棒锤其他活性部位的急性毒性,以热板法和扭体法考察了不同剂量铁棒锤氯仿部位对小鼠的镇痛作用.结果表明:铁棒锤不同部位对小鼠急性毒性强度差别较大,氯仿部位的毒性最强,正丁醇和石油醚部位次之,三者的LD50分别为37.514,6766.928,5492.337 mg/kg.不同剂量的铁棒锤氯仿部位均能提高小鼠热板痛阈值,呈剂量依赖性关系.20mg/kg铁棒锤60 min时的镇痛百分率为108.7%,远低于阳性对照10 mg/kg吗啡组(261.6%),但高于同剂量的铁棒锤总提物组(75.2%).不同剂量的铁棒锤氯仿部位均能有效抑制冰醋酸对所致小鼠扭体反应,呈剂量依赖性关系.20 mg/kg组的扭体抑制率为76.4%,明显高于200 mg/kg阿司匹林(50.5%)和20 mg/kg总提物组(51.0%).说明铁棒锤氯仿部位具有显著的毒性和镇痛活性呈剂量依赖性,推测其镇痛活性与毒性存在一定的关联.