利血平与优降宁对动物痛阈和吗啡镇痛作用影响因素探讨

采用三种测痛方法,观察了利血平、优降宁对小鼠、大鼠正常痛阈和吗啡镇痛作用的影响,结果表明:ip利血平2 mg/kg,优降宁100 mg/kg均能明显抑制小鼠扭体反应;ip利血平1 mg/kg能明显提高小鼠热板反应时间,但ip优降宁75 mg/kg无明显影响;ip利血平6 mg/kg,优降宁75 mg/kg对大鼠甩尾反应时间均无明显影响;利血平(小鼠0.5～1.0 mg/kg,大鼠2 mg/kg ip)能明显对抗吗啡镇痛作用;优降宁(小鼠35 mg/kg,大鼠50 mg/kg ip)能明显增强吗啡镇痛作用,并能“逆转”利血平对抗吗啡镇痛作用。其“逆转”作用的强弱取决于利血平、优降宁给药的先后次序。     

不同药物对眼镜蛇神经毒素镇痛效应的影响

用电尾嘶叫法测量大鼠病阈。给大鼠侧脑室注射相当于1/10im有效量的眼镜蛇神经毒素(NT)可明显提高大鼠痛阈。利血平5mg/kg,ip并不影响NT的镇痛作用。纳洛酮3mg/kg,ip仅能轻度降低NT的镇痛作用。阿托品1mg/kg,im却能完全拮抗NT的镇痛效应。在对吗啡急性耐受的大鼠上,NT仍能产生明显的镇痛效应。结果提示,NT的镇痛部位可能位于中枢神经系统内。其镇痛机理可能涉及中枢的乙酰胆碱能系统。     

两面针结晶8的解痉和镇痛作用研究

结晶-8,是从两面针提出的一种单体。当浓度为1×10^-6～1×10^-4g/ml对正常离体豚鼠回肠活动无影响,但对乙酰胆硷、匹鲁卡品、氯化钡及组织胺所致肠肌收缩有明显的松弛作用;结晶-8腹腔注射10 mg/kg有明显抑制小鼠扭体反应;8～20 mg/kg明显提高家兔及大鼠痛阈,200μg/kg脑室注射亦有明显提高大鼠痛阈。其镇痛作用不被丙烯吗啡(5 mg/kg)所拮抗,而被利血平(4 mg/kg)所对抗。表明结晶-8的解痉作用直接作用于肠平滑肌。而镇痛作用具有中枢性,与吗啡受体无直接关系,但与脑内单胺类介质有关。     

痛稳素和痛稳素(10～17)对孤啡肽对抗内吗啡肽-1及内吗啡肽-2镇痛作用的影响

目的研究痛稳素及其碳末端八肽在小鼠脑内对孤啡肽对抗内吗啡肽-1及内吗啡肽-2镇痛作用的影响。方法以固相多肽合成法合成了痛稳素及其碳末端八肽,侧脑室注射孤啡肽、痛稳素及其碳末端八肽,用辐射热甩尾法测定痛阈。结果孤啡肽可对抗内吗啡肽-1及内吗啡肽-2的镇痛作用;痛稳素及其碳末端八肽不影响小鼠的基础痛阈,但可逆转孤啡肽对抗内吗啡肽-1及内吗啡肽-2的镇痛作用。结论痛稳素及其碳末端八肽在脊髓以上水平可逆转孤啡肽对抗内吗啡肽-1及内吗啡肽-2的镇痛作用。     

滇西嘟拉碱甲的镇痛和身体依赖性研究

用扭体法、热板法、光热-甩尾法和甲醛致痛法证实Bul有明显镇痛作用。连续给药9 d,镇痛作用无耐受现象。小鼠跳跃反应试验阴性;Bul对吗啡依赖大鼠或猴的戒断症状,均无替代作用。Bul的镇痛作用不能被纳络酮翻转;利血平可取消Bul的镇痛作用,补充5-HT或5-HTP能翻转利血平取消Bul的镇痛作用。     

不同剂量地西泮对小鼠吗啡镇痛效果的影响

目的观察不同剂量地西泮对吗啡镇痛效果的影响。方法30只小鼠随机均分为生理盐水组(NS组)、D1组(地西泮8 mg/kg)和D2组(地西泮16 mg/kg),连续注射14 d,第15日停止给药并正常饲喂1 d,第16日各组注射吗啡0.125 mg/kg,分别在地西泮注射及吗啡注射后以热甩尾法测定小鼠痛阈。结果不同剂量地西泮对吗啡镇痛效果的影响有显著性差异,D1组和D2组较NS组痛阈增加(P<0.01),而D1组与D2组间无显著性差异(P>0.05)。结论地西泮能显著增强吗啡的镇痛作用,且可能随剂量的增加增效的幅度有所降低。     

痛稳素碳末端八肽翻转孤啡肽对抗吗啡镇痛的作用

目的　观察痛稳素碳末端八肽在小鼠脑内对孤啡肽对抗吗啡的镇痛作用的影响。方法　固相多肽合成法合成了痛稳素碳末端八肽 ,用辐射热甩尾法测定痛阈 ,观察 (1)小鼠脑室注射 (icv)孤啡肽对吗啡镇痛作用的影响 ;(2 )小鼠脑室注射 (icv)痛稳素碳末端八肽对小鼠基础痛阈的影响 ;(3)小鼠脑室联合注射 (icv)痛稳素碳末端八肽和孤啡肽对吗啡镇痛作用的影响。结果　孤啡肽可对抗吗啡的镇痛作用 ;痛稳素碳末端八肽本身不影响小鼠的基础痛阈 ,但可逆转孤啡肽对抗吗啡的镇痛作用。结论　痛稳素碳末端八肽在脊髓以上水平可以逆转孤啡肽对抗吗啡的镇痛作用     

东亚钳蝎毒的提取物Tityustoxin-Ⅲ镇痛作用及其机理的研究

本文报告了蝎毒素-Ⅲ的镇痛作用及其作用机制。蝎毒素-Ⅲ(ti?yusioxin-Ⅲ)是一种镇痛活性多肽。它是从东亚钳蝎毒中经过Cm-sephaden G-50柱层析提取,再用Sephaden G50凝胶过滤纯化而成。小鼠扭体实验表明TT-Ⅲ的镇痛作用较粗毒强三倍,较安痛定作用亦强。小鼠光热甩尾法实验结果TT-Ⅲ(0.424mg/kg iv)使痛阈(甩尾反应时间)提高4倍。侧脑室注射TT-Ⅲ14μg/kg抑制皮层诱发电位N波82±12%,与等剂量吗啡相似。利血平化大鼠,TT-Ⅲ对皮层诱发电位N波失去抑制作用,Ⅲ由侧脑室注入5HT后,TT-Ⅲ对N波的抑制率恢复到68.9%。     

痛稳素碳末端八肽翻转弧啡肽对抗吗啡镇痛的作用

目的：观察痛稳素碳末端八肽在小鼠脑内对孤啡肽对抗吗啡的镇痛作用的影响。方法：固相多肽合成法合成了痛稳素碳末端八肽，用辐射热甩尾测定痛阈，观察（1）小鼠脑室注射（icv)孤啡肽对吗啡镇痛作用的影响；（2）小鼠脑室注射（icv）痛隐素碳末端八肽对小鼠基础痛阈的影响；（3）小鼠脑室联合注射（icv）痛稳素碳末端八肽和孤啡肽对吗啡镇痛作用的影响。结果：弧啡肽 抗吗啡的镇痛作用；痛稳素碳末端八肽本身不影响小鼠的基础痛阈，但可逆转孤啡肽对抗吗啡的镇痛作用。结论：痛稳素碳末端八肽在脊髓以上水平可以逆转弧肽对抗吗啡的镇痛作用。     

人参茎叶皂甙对正常和利血平化小鼠心肌cAMP和cGMP含量的影响

口服人参茎叶皂甙25mg/kg,连续服用7天组小鼠心肌 cAMP 含量显著升高(p<0.01),而对 cGMP 含量无明显影响;50mg/kg GSL 对 cAMP,cGMP 含量均无明显影响。对利血平化小鼠,50mg/kg 能明显提高小鼠心肌中 cAMP 的含量(p<0.01),对 cGMP 含量影响不明显。cAMP/cGMP 比值提示,25mg/kg 和50mg/kg GSL 对 cAMP/cGMP 比值均增高;对利血平化小鼠心肌 cAMP/cGMP 比值无明显变化。     

加钖果宁的镇痛作用及其作用机制

野花椒系芸香科植物(Zanthoxylum simulans Hance),其根皮有止痛及局麻作用。其水溶性生物碱有肌松作用,曾用于外科手术作为中麻辅助用药。常志青从中分离到加钖果宁[(—)edulinine,简称加钖碱,下同],并发现有镇痛及中枢抑制作用。本文进一步证明其镇痛作用及其作用机制与阿片受体有关。     

Potentiation of morphine analgesia in rats given a single exposure to restraint stress immobilization.

Rats exposed to restraint stress and injected with morphine show significantly greater increases in tail-flick latency compared to unstressed rats. However, it is not necessary for rats to be restrained at the time of testing to elicit a potentiated analgesic response to morphine. We reported recently that analgesia induced by 4.0 mg/kg morphine was significantly potentiated in rats that had been restrained for only 1 h at 24 h prior to testing. One purpose of the present study was to extend this observation by determining the ability of a single exposure to restraint stress to potentiate dose-dependently morphine (0.0, 2.0, 4.0, and 8.0 mg/kg)-induced analgesia in the tail-flick test. A second purpose was to assess the generality of the phenomenon by determining whether prior restraint would potentiate the analgesic effect of morphine in another common analgesic assay, the hot-plate test. Dose- and time-course (20-120 min) curves for morphine were generated in rats exposed to one of two treatments: no restraint stress (NS) and a single exposure to 1 h of restraint (RS). Rats subjected to 1 h of restraint and tested 24 h later displayed significant time- and dose-dependent potentiation (1.3-2.0-fold) of morphine-induced analgesia compared to unstressed rats in both the tail-flick and hot-plate tests. These results demonstrate that a single period of restraint is sufficient to activate the mechanisms responsible for potentiation of morphine-induced analgesia and that the degree to which stress modified morphine's analgesia can be demonstrated using both the tail-flick and hot-plate assays.     

The effect of adenosine receptor agonists on analgesic effects of morphine

The effect of adenosine, S-phenylisopropyladenosine (S-PIA) and dipyridamole (an adenosine reuptake inhibitor) on the analgesic action of morphine in mice and rats was investigated in the hot-plate (56 degrees C) and tail immersion (52 degrees C) tests. Adenosine, 50 and 100 mg/kg, induced analgesia in mice and rats in the hot-plate test and potentiated the action of morphine (particularly in mice). The analgesic effects of adenosine were completely abolished by caffeine (10 mg/kg in mice and rats), and partially inhibited by naloxone (1 mg/kg, only in mice). S-PIA given alone (0.6 mg/kg) produced in mice some analgesic effect in the hot-plate test: the effect was abolished by caffeine and partially by naloxone. The effect of S-PIA on the action of morphine depends on the dose and the animal species. Dipyridamole alone did not affect the reactivity of animals in tests for analgesia, but potentiated the action of morphine.     

松潘乌头总碱的镇痛作用和身体依赖性的实验研究

松潘乌头总碱(TAS)ip,ig,sc给药均呈剂量依赖性抑制小鼠热板、扭体及嘶叫反应。TAS的镇痛作用明显强于高乌甲素。连续给药7 d,TAS的镇痛作用无耐受现象。小鼠跳跃试验和竖尾试验均为阴性结果,提示TAS是一种不同于吗啡的非成瘾性镇痛剂。     

胍丁胺对小鼠和大鼠镇痛及增强吗啡镇痛

AIM: To study the effect of agmatine on pain and morphine analgesia. METHODS: The effect of agmatine on pain was observed in mouse heat radiant tail-flick test, mouse acetic acid writhing test, and rat 4% saline test. Its enhancing effect on analgesia of morphine and clonidine was assessed in rat and mouse heat radiant tail-flick tests. RESULTS: Agmatine did not significantly prolong tail-flick latency of mice, but reduced the number of acetic acid-induced writhing of mice and inhibited writhing responses to saline completely. It potentiated the analgesic effects of morphine and clonidine in dose-dependent manner and decreased the analgesic ED50 of morphine and clonidine by more than 75% in mouse heat radiant tail-flick test. These effects of agmatine were antagonized by idazoxan. CONCLUSION: Agmatine has weak analgesic effects and potentiates morphine and clonidine analgesia by activation of imidazoline receptors.     

A long-form α-neurotoxin from cobra venom produces potent opioidindependent analgesia

AIM: In light of the antinociceptive activity of the short-chain neurotoxin, cobrotoxin, and other acetylcholine antagonists, the antinociceptive activity and mechanisms of cobratoxin (CTX), a long-chain postsynaptic alpha-neurotoxin, was investigated in rodent pain models. METHODS: CTX was administered intraperitoneally (30, 45, 68 microg/kg), intra-cerebral ventricularly (4.5 microg/kg) or microinjected into periaqueductal gray (PAG; 4.5 microg/kg). The antinociceptive action was tested using the hot-plate and acetic acid writhing tests in mice and rats. The involvement of the cholinergic system and opioid system in CTX-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im; or 10 mg/kg, ip) or naloxone (1 and 5 mg/kg, ip). The effect of CTX on motor activity was tested using the Animex test. RESULTS: CTX exhibited a dose-dependent analgesic action in mice as determined by both the hot-plate and acetic acid writhing tests. The peak effect of analgesia was seen 3 h after administration. In the mouse acetic acid writhing test, the intra-cerebral ventricular administration of CTX at 4.5 microg/kg (1/12th of a systemic dose) produced marked analgesic effects. Microinjection of CTX (4.5 microg/kg) into the PAG region did not elicit an analgesic action in rats in the hot-plate test. Atropine at 0.5 mg/kg (im) and naloxone at 1 and 5 mg/kg (ip) both failed to block the analgesic effects of CTX, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CTX in the mouse acetic acid writhing test. Acetylsalicylic acid (300 mg/kg) did not enhance the analgesic effects of CTX. At the highest effective dose of 68 microg/kg the neurotoxin did not change the spontaneous mobility of mice. CONCLUSION: CTX has analgesic effects, which are mediated in the central nervous system though not through the PAG. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CTX.     

维生素K3中枢镇痛效应的探讨

经由大鼠、小鼠甩尾及兔甩头法测痛,证实k₃具有剂量依赖的镇痛作用。兔侧脑室微量注射k₃亦有显著镇痛效应。k₃的镇痛作用可被阿片拮抗剂纳络酮所拮抗。实验观察到k₃与吗啡的镇痛效应间存在交叉耐受现象。一定浓度的k₃可抑制电场刺激所致豚鼠回肠纵肌标本的收缩,这一效应亦可被纳络酮部分逆转。小鼠经k₃预处理后对k₃的镇痛产生耐受;连续k₃大剂量预处理后纳络酮激发不产生跳跃。     

褪黑素的镇痛作用和身体依赖性实验

本文在小鼠上观察褪黑素的镇痛作用和身体依赖性。热板法痛阈测试表明,腹腔注射（ｉｐ）褪黑素可产生显著的镇痛效应,并呈剂量依赖性。小鼠跳跃反应试验表明,在２ｄ内７次皮下注射（ｓｃ）褪黑素或吗啡后,再ｉｐ纳洛酮,吗啡组小鼠出现显著的跳跃反应,而褪黑素组则无;小鼠竖尾反应表明,ｉｐ不同剂量褪黑素,小鼠都未出现竖尾反应。上述结果提示,褪黑素对小鼠无身体依赖性作用,这为其开发研究提供了动物学实验依据