左旋精氨酸及左旋精氨酸脱羧酶抗血清对吗啡镇痛及耐受的影响

目的:分析左旋精氨酸及左旋精氨酸脱羧酶(L-ADC)对吗啡镇痛及其所致耐受的影响。方法:用家兔制备L-ADC多克隆抗体;以小鼠热辐射甩尾法和小鼠55℃热板测痛模型分析此抗体及左旋精氨酸对吗啡镇痛和耐受的影响。结果:在热辐射甩尾和热板测痛模型中,0.5-50mg·kg~(-1)的左旋精氨酸(sc)不影响吗啡镇痛和耐受(P>0.05)。L-ADC抗血清(脑室注射,1:1000-1:10稀释)能对抗吗啡镇痛作用,在热辐射甩尾和热板测痛模型中,它能使吗啡可能最大镇痛百分率分别从94.3％和80.6％下降到57.7％和42.9％(P<0.01)。吗啡连续处理小鼠3d后形成耐受:在热辐射甩尾和热板测痛模型中,吗啡的可能最大镇痛百分率分别从90.3％和80.3％下降到47.2％和40.5％;L-ADC抗血清能进一步加重吗啡所致耐受,其可能最大镇痛百分率进一步下降至19.8％和27.7％(P<0.01)。结论:L-ADC可能参与调节了吗啡镇痛及耐受形成过程;而左旋精氨酸不影响吗啡镇痛和耐受。     

咪唑克生对吗啡镇痛、耐受和身体依赖的影响

目的:观察咪唑克生对吗啡镇痛及吗啡所致耐受和躯体依赖的影响.方法:采用小鼠醋酸扭体实验和55℃热板实验观察咪唑克生对基础痛阈及吗啡镇痛作用的影响;采用小鼠热辐射甩尾实验和小鼠55℃热板实验观察咪唑克生对吗啡耐受形成过程的影响;采用大鼠、小鼠身体依赖模型观察咪唑克生对吗啡所致身体依赖的影响.结果:咪唑克生(3-9mg/kg)能显著降低小鼠基础痛阈,抑制吗啡镇痛;加重吗啡所致耐受;诱发大、小鼠发生戒断综合征.结论:咪唑啉受体参与痛阈形成;咪唑克生能抑制吗啡镇痛,加重吗啡所致耐受;并诱发吗啡依赖性动物发生戒断综合征.     

利鲁唑对吗啡镇痛、耐受和依赖作用的影响(英文)

目的　研究利鲁唑对阿片镇痛、耐受及躯体功能的调节。方法　采用冰醋酸扭体 ,5 5℃热板法和热辐射甩尾法观察利鲁唑对小鼠痛阈及吗啡镇痛效应的影响 ;采用小鼠急性和慢性吗啡耐受模型及小鼠吗啡依赖模型 ,观察利鲁唑对吗啡耐受和依赖的作用。结果　单独皮下注射利鲁唑 2 .5～ 10mg·kg- 1在以上 3种模型无镇痛作用 ,然而能剂量依赖性地增强吗啡镇痛效应。利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地对抗吗啡引起的急性和慢性耐受。在小鼠吗啡依赖模型中 ,利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地抑制吗啡戒断症状的产生。结论　利鲁唑自身无镇痛作用 ,但能显著增强吗啡镇痛效应 ,并能预防吗啡所引起的耐受和依赖     

Analgesic effect of agmatine and its enhancement on morphine analgesia in mice and rats

目的：观察胍丁胺镇痛和对吗啡镇痛的作用．方法：在小鼠热辐射甩尾,醋酸扭体,大鼠４％盐水实验中观察胍丁胺的镇痛作用;在小鼠和大鼠热辐射甩尾实验中观察其对吗啡和可乐定镇痛的作用．结果：胍丁胺不延长小鼠甩尾潜伏期,使小鼠醋酸扭体次数减少,完全抑制大鼠盐水扭体．在小鼠甩尾实验中,胍丁胺剂量依赖性地增强吗啡和可乐定的镇痛,使吗啡和可乐定的镇痛ＥＤ５０减小了７５％．胍丁胺的上述作用可被咪唑克生所对抗．结论：胍丁胺通过激动咪唑啉受体而具有较弱镇痛和加强吗啡及可乐定镇痛作用     

胍丁胺代谢产物腐胺对吗啡镇痛、耐受和依赖的影响

目的观察腐胺对吗啡镇痛、耐受及依赖的影响,探讨腐胺治疗阿片耐受性和依赖性的潜力。方法小鼠醋酸扭体模型和55℃热板法测痛阈;吗啡恒定剂量给药制备耐受模型,55℃热板法测痛阈;吗啡递增剂量给药制备依赖模型,纳洛酮催促观察戒断症状,以胍丁胺(40 mg.kg-1,ig)为阳性对照药,腐胺灌胃给药剂量分别为10,20,40,80 mg.kg-1。结果在小鼠醋酸扭体模型中腐胺具有镇痛作用;而在小鼠55℃热板实验中,腐胺本身无镇痛作用,能较弱地增强吗啡镇痛;腐胺能够减弱吗啡耐受的形成,对已形成的吗啡耐受也有治疗作用;腐胺能够减弱吗啡躯体依赖的形成和表达。结论腐胺和胍丁胺具有相似的生物学活性,具有治疗阿片耐受和依赖的潜力。     

河豚毒素与吗啡联合用药对吗啡依赖性与镇痛耐受作用的影响

目的:研究河豚毒素(tetrodotoxin,TTX)与吗啡联合使用对吗啡依赖性及镇痛耐受作用的影响。方法:采用吗啡依赖性小鼠模型及热板实验,评价单独使用吗啡(2.5 ml.kg-1)以及联合给药(吗啡2.5 mg·kg-1+TTX 0.5μg·kg-1、吗啡2.5 mg·kg-1+TTX 1.0μg·kg-1)对纳洛酮催促戒断症状及镇痛耐受性的影响。结果:联合用药可以抑制吗啡依赖性小鼠戒断后体重的丢失,明显抑制吗啡依赖小鼠纳洛酮催促后的跳跃反应,抑制小鼠热板实验的潜伏期时间的增加。结论:TTX与吗啡联合用药可以抑制吗啡的依赖性与镇痛耐受作用的产生。     

三氟拉嗪对吗啡镇痛耐受性的翻转作用

目的··:研究三氟拉嗪对吗啡镇痛耐受性的影响。方法··:热板测痛法,测定三氟拉嗪对小鼠热板(55℃)痛阈值(s)的影响;慢性吗啡处理使小鼠对吗啡的镇痛作用产生耐受性 ,观察低剂量三氟拉嗪对吗啡耐受小鼠最大镇痛效率的影响。结果··:(1)三氟拉嗪(2-20mg·kg-1)呈剂量依赖性延长小鼠的热板(55℃)痛阈值(s) ;(2)慢性吗啡处理使6mg·kg-1 吗啡最大镇痛效率降低42.2%(P<0.05),9mg·kg-1 吗啡最大镇痛效率降低9.8%(P>0.05) ;(3)合用低剂量三氟拉嗪(2mg·kg-1)和吗啡(6mg.kg-1)可以使吗啡耐受小鼠的最大镇痛效率提高47.9 %(P<0.01),其最大镇痛效率与单独急性吗啡(6mg·kg-1)处理相同。结论··:三氟拉嗪对小鼠的吗啡镇痛耐受性存在翻转作用     

1,6-二(4-苯乙基-1-甲基-1-哌嗪基)己烷二溴化物的镇痛活性研究

目的　研究哌嗪类新化合物 1,6 二 (4 苯乙基 1 甲基 1 哌嗪基 )己烷二溴化物 (97 9 G4 )的镇痛作用及机制。方法　通过醋酸扭体模型、热板、甩尾、纳洛酮拮抗试验及豚鼠回肠离体标本研究样品的镇痛活性及机制。结果　sc 97 9 G4 5mg·kg-1即可有效抑制小鼠扭体反应 (P <0 0 5 ) ,ID50为 8 8mg·kg-1;sc 4 0mg·kg-1、icv 2 5 μg·kg-1均可延长热板实验的舔足阈 (P <0 0 5 ) ;sc 2 0mg·kg-1可延长甩尾试验的潜伏期 (P <0 0 1) ;纳洛酮可拮抗其镇痛活性 ;97 9 G4可激动豚鼠回肠离体标本上的阿片受体。结论　 97 9 G4具有的镇痛活性 ,主要作用部位在中枢 ,其镇痛活性可被纳洛酮拮抗 ,但作用特点有别于吗啡     

右酮洛芬对实验动物的解热镇痛和抗炎作用

目的 :研究右酮洛芬的解热镇痛和抗炎作用。方法 :采用小鼠热板法和热辐射甩尾法 ;角叉菜胶诱导的大鼠和伤寒疫苗诱导的兔体温升高 ;二甲苯诱导的小鼠耳水肿 ,大鼠角叉菜胶诱导的足肿胀和大鼠棉球肉芽肿胀实验模型。结果 :右酮洛芬( 7.5,15,30mg·kg- 1)能明显延长小鼠热板和热辐射甩尾的痛阈时间 ;右酮洛芬 ( 7.5,15,30mg·kg- 1)对角叉菜胶诱导的大鼠体温升高 ,右酮洛芬( 1.9,3.8,7.5mg·kg- 1)对伤寒疫苗诱导的兔体温升高均有明显的降温作用 ;右酮洛芬 ( 7.5,15,30mg·kg- 1)对二甲苯诱导的小鼠耳水肿有显著的抑制作用 ;右酮洛芬 ( 3.8,7.5,15mg·kg- 1)对大鼠角叉菜胶引起的足肿胀及棉球诱导的大鼠肉芽肿均有显著的抑制作用。结论 :实验结果表明 ,右酮洛芬具有良好的解热镇痛和抗炎作用     

三氟拉嗪的抗伤害作用及其作用机理

应用小鼠热板法和醋酸扭体法伤害实验 ,评价三氟拉嗪的抗伤害作用 ,并对其作用机理进行探讨 .结果表明 :在热板法伤害实验中 ,三氟拉嗪 (2～ 2 0mg·kg- 1)剂量依赖性地延长热板伤害反应的潜伏期 ,三氟拉嗪 (2mg·kg- 1)和吗啡 (1,3和 6mg·kg- 1)合并使用 ,增加吗啡抗伤害的作用和效率(2 9.4 %～ 5 4 .4 % ) ;在醋酸扭体法伤害实验中 ,三氟拉嗪 (0 .1～ 3mg·kg- 1)非常显著地抑制醋酸伤害刺激所致小鼠扭体反应的次数 ,增加扭体反应的潜伏期 ,呈剂量依赖性 .进一步研究结果表明 :μ受体拮抗剂纳洛酮 (1～ 9mg·kg- 1)和多巴胺 1(DA1) /多巴胺 2 (DA2 )受体激动剂阿扑吗啡 (1～ 9mg·kg- 1)对三氟拉嗪的抗伤害作用无翻转作用 .这些结果提示 :三氟拉嗪具有一定的抗伤害刺激的药理作用 ,但是中枢神经系统中的 μ受体和DA2 受体不参与三氟拉嗪的抗伤害作用     

Central components in the antinociceptive activity of dipyrone in mice

Dipyrone is classified as a nonsteroidal anti-inflammatory drug. It has analgesic, antipyretic and anti-inflammatory properties and exerts its analgesic effect via both peripheral and central action. Dipyrone at the dose of 250 and 500 mg/kg showed dose-dependent antinociceptive activity in the hot plate, tail flick tests to radiant heat and tail clip test and the writhing test induced by acetic acid in mice. The antinociceptive effects of dipyrone (500 mg/kg) were antagonized by naloxone (1, 2, 5 mg/kg) in the tail flick test to radiant heat and tail clip test and hot plate tests but not in the writhing test. Cyproheptadine (100 g/kg) decreased the antinociceptive effect of dipyrone. There was an increase in the antinociceptive effects of dipyrone (500 mg/kg) when combined with buspiron (0.5 mg/kg) in the tail flick test to radiant heat and tail clip test. The results provide evidence for a central antinociceptive effect of dipyrone antagonized by naloxone which suggests that its activity may also involve the serotoninergic system.     

生长抑素及其拮抗剂对小鼠吗啡镇痛的影响(英文)

AIM: To study the effects of somatostatin (SST) andits antagonist cyclo- (7 - aminoheptanoyl- Phe-D-Trp-Lys-Thr [Bzl]) (SSA) on morphine-induced analgesia.METHODS: The pain assays were the hot plate andthe tail flick test. RESULTS: SST or SSA per seadministered intracerebrally at the doses of 0.1 and Img/mouse did not change the pain threshold of miceboth in the hot plate and in the tail flick test.However, at the higher dose (10 mg/mouse), SST andSSA decreased the pain threshold in the tail flick test     

生长抑素及其拮抗剂对小鼠吗啡镇痛的影响

AIM: To study the effects of somatostatin (SST) and its antagonist cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr [Bzl]) (SSA) on morphine-induced analgesia. METHODS: The pain assays were the hot plate and the tail flick test. RESULTS: SST or SSA per se administered intracerebrally at the doses of 0.1 and 1 mg/mouse did not change the pain threshold of mice both in the hot plate and in the tail flick test. However, at the higher dose (10 mg/mouse), SST and SSA decreased the pain threshold in the tail flick test only. SST and SSA administered at the dose of 0.1 mg/mouse did not change morphine-induced analgesia. By contrast, SST and SSA at the doses of 1 and 10 mg/mouse reduced morphine analgesia effects both in the hot plate as well as in the tail flick test. CONCLUSION: Our results indicate that SSA as well as SST may be useful in studying pain mechanisms.     

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.     

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with mu opioid receptor and alpha2-adrenoceptor agonists in acute pain models in mice

1. Cannabinoid receptor agonists elicit analgesic effects in acute and chronic pain states via spinal and supraspinal pathways. We investigated whether the combination of a cannabinoid agonist with other classes of antinociceptive drugs exerted supra-additive (synergistic) or additive effects in acute pain models in mice. 2. The interactions between the cannabinoid agonist CP55,940, alpha2-adrenoceptor agonist dexmedetomidine and mu-opioid receptor agonist morphine were evaluated by isobolographic analysis of antinociception in hot plate (55 degrees C) and tail flick assays in conscious male Swiss mice. Drug interactions were examined by administering fixed-ratio combinations of agonists (s.c.) in 1:1, 3:1 and 1:3 ratios of their respective ED50 fractions. 3. CP55,940, dexmedetomidine and morphine all caused dose-dependent antinociception. In the hot plate and tail flick assays, ED50 values (mg kg(-1)) were CP55,940 1.13 and 0.51, dexmedetomidine 0.066 and 0.023, and morphine 29.4 and 11.3, respectively. Synergistic interactions existed between CP55,940 and dexmedetomidine in the hot plate assay, and CP55,940 and morphine in both assays. Additive interactions were found for CP55,940 and dexmedetomidine in the tail flick assay, and dexmedetomidine and morphine in both assays. 4. Thus, an alpha2-adrenoceptor agonist or mu opioid receptor agonist when combined with a cannabinoid receptor agonist showed significant synergy in antinociception in the hot plate test. However, for the tail flick nociceptive response to heat, only cannabinoid and mu opioid receptor antinociceptive synergy was demonstrated. If these results translate to humans, then prudent selection of dose and receptor-specific agonists may allow an improved therapeutic separation from unwanted side effects.     

Modulation of morphine antinociception in the mouse by endogenous nitric oxide.

1. L-Arginine (100-1000 mg kg-1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5-10 mg kg-1 s.c.) assessed in mice using three different tests: hot plate, tail-flick and acetic acid-induced writhing. D-Arginine (up to 1000 mg kg-1 p.o. or i.p.) was ineffective. 2. NG-Monomethyl-L-arginine (L-NMMA, 5-50 mg kg-1 i.p.) and NG-nitro-L-arginine methyl ester (L-NAME, 5- 30 mg kg-1 i.p.), but not NG-nitro-D-arginine methyl ester (D-NAME, 30 mg kg-1 i.p.), reversed in all assays the effect of L-arginine on morphine-induced antinociception. 3. Morphine (10 mg kg-1 s.c.), L-arginine (1000 mg kg-1 p.o.) or L-NAME (30 mg kg-1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. 4. These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes.