精氨酸及精氨酸脱羧酶抗体对痛阈及吗啡镇痛作用的影响(英文)

目的进一步阐明胍丁胺对阿片药理作用的影响。方法采用小鼠醋酸扭体法、小鼠热辐射甩尾法、小鼠热板法评价了精氨酸及精氨酸脱羧酶抗体对痛阈、吗啡镇痛及其耐受作用的影响。结果在小鼠醋酸扭体实验中,脑室注射精氨酸能剂量依赖性地抑制小鼠扭体次数,最大抑制率达84 %。在小鼠热辐射甩尾模型中,精氨酸不影响小鼠的甩尾时间,但能剂量依赖性地增强吗啡的镇痛作用,使吗啡2 .5 mg·kg-1的最大可能镇痛百分率从23 %增加到71 %。此外,在小鼠热辐射甩尾实验中,精氨酸能抑制吗啡100 mg·kg-1所诱导的急性耐受。精氨酸上述作用可被咪唑啉受体拮抗剂咪唑克生(3mg·kg-1,ip)所抑制。在小鼠热辐射甩尾实验和小鼠55℃热板实验中,精氨酸脱羧酶抗体能抑制吗啡镇痛,并能加重吗啡所致的耐受。结论上述结果提示,精氨酸及精氨酸脱羧酶在痛阈、吗啡镇痛及吗啡依赖形成过程中具有重要作用。     

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。     

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     

新疆阿魏挥发油对吗啡依赖大鼠、小鼠戒断症状的作用

目的 观察新疆阿魏挥发油(FSEO)对小鼠的镇痛作用以及对吗啡依赖大鼠、小鼠戒断症状的影响.方法 采用扭体法、热板法观察FSEO对小鼠的镇痛作用,吗啡依赖大鼠、小鼠采用纳洛酮催促戒断,观察FSEO对戒断症状的影响.结果 灌服不同剂量FSEO可不同程度的抑制化学刺激所致的小鼠扭体反应,提高热板致痛小鼠的痛阈值,扭体镇痛的...     

Effects of agmatine on tolerance to and substance dependence on morphine in mice

目的：观察胍丁胺对吗啡所致耐受和依赖的作用．方法：分别在小鼠耐受和跳跃实验中观察胍丁胺抑制吗啡所致耐受和物质依赖的作用．结果：胍丁胺０１２５－２５ｍｇ·ｋｇ－１剂量依赖性地阻止小鼠对吗啡耐受．用吗啡预处理小鼠使吗啡镇痛ＥＤ５０（２０１,１４４－２８０ｍｇ·ｋｇ－１）与盐水组相比（６３,５１－７８ｍｇ·ｋｇ－１）增加３倍以上．用胍丁胺和吗啡共同预处理小鼠则使吗啡丧失引起耐受的能力．胍丁胺（２５－１０ｍｇ·ｋｇ－１）剂量依赖性地抑制由纳洛酮引起的吗啡依赖小鼠之戒断跳跃和体重减轻．用胍丁胺和吗啡共同处理小鼠使引起小鼠之戒断跳跃所需纳洛酮ＥＤ５０（２１４,１８４－２４ｍｇ·ｋｇ－１）较吗啡处理组（２５,２１－２８ｍｇ·ｋｇ－１）增大８倍．胍丁胺的上述作用均被咪唑克生所阻断．结论：胍丁胺通过激活咪唑啉受体而阻止小鼠对吗啡耐受和依赖．     

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。     

吗啡长期给药后大鼠脑内MAO—B活性及咪唑啉受体的下调

目的:探讨吗啡长期给药处理后大鼠不同脑区MAO-B活性及咪唑啉受体含量的变化。方法:用[~3H]咪唑克生配体结合试验测定咪唑啉受体含量,用高效液相色谱法测定MAO-B活性。结果:咪唑克生和吗啡能剂量依赖性地抑制大鼠脑匀浆MAO-B活性。咪唑啉受体的内源性配体胍丁胺既不影响MAO-B活性,也不影响咪唑克生及吗啡对MAO-B活性的抑制作用。吗啡连续给药16d后大鼠大脑、海马、丘脑、纹状体及小脑内MAO-B活性均显著下调(P<0.01)。纳洛酮及咪唑克生单次给药对吗啡依赖大鼠上述脑区MAO-B活性均没有进一步影响;胍丁胺伴随吗啡给药后能显著抑制吗啡降低MAO-B活性的作用。吗啡连续给药后大鼠皮层和小脑咪唑啉受体数量减少而亲和力上调(P<0.05)或P<0.01)。结论:MAO-B活性与吗啡依赖大鼠发生戒断综合征相关,但与胍丁胺对吗啡镇痛作用的影响无关;胍丁胺对吗啡药理作用的影响与其激活咪唑啉受体有关。     

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。     

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。     

济泰片对小鼠诱发性疼痛及对吗啡躯体依赖小鼠戒断症状的影响

目的:观察济泰片对诱发的小鼠疼痛的镇痛作用和对吗啡依赖小鼠催促戒断症状的影响。方法:(1)采用小鼠醋酸扭体法,观察经胃给予2.4 g.kg-1,3.6 g.kg-1,4.8 g.kg-1三种浓度济泰片的镇痛作用;(2)采用小鼠热板法,观察经胃给予6.0 g.kg-1,9.0 g.kg-1,12.0 g.kg-1三种浓度济泰片的镇痛作用;(3)采用连续递增给药法建立吗啡依赖小鼠模型,观察经胃给予1.2 g.kg-1,2.4 g.kg-1,3.6 g.kg-1济泰片后对吗啡依赖小鼠的纳洛酮催促戒断跳跃反应的影响。结果:(1)济泰片溶液呈剂量依赖性的抑制醋酸诱发的小鼠扭体次数(P<0.01),对扭体次数的抑制率最高可达71.7%;(2)济泰片溶液能明显提高热板法诱发的小鼠疼痛痛阈值,其镇痛的ED50=8.34 g.kg-1;(3)伴随给予济泰片溶液能剂量依赖性地抑制纳洛酮催促所引起的吗啡躯体依赖戒断症状,使吗啡依赖小鼠跳跃次数明显减少(P<0.01)。结论:济泰片对诱发的小鼠疼痛有明显的镇痛作用,并能抑制吗啡躯体依赖小鼠的戒断症状。     

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     

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     

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.     

Analgesic activity of ZC88, a novel N-type voltage-dependent calcium channel blocker, and its modulation of morphine analgesia, tolerance and dependence

ZC88 is a novel non-peptide N-type voltage-sensitive calcium channel blocker synthesized by our institute. In the present study, the oral analgesic activity of ZC88 in animal models of acute and neuropathic pain, and functional interactions between ZC88 and morphine in terms of analgesia, tolerance and dependence were investigated. In mice acetic acid writhing tests, ZC88 (10-80 mg/kg) administered by oral route showed significant antinociceptive effects in a dose-dependent manner. The ED50 values of ZC88 were 14.5 and 14.3 mg/kg in male and female mice, respectively. In sciatic nerve chronic constriction injury rats, mechanical allodynia was ameliorated by oral administration of ZC88 at doses of 14, 28 and 56 mg/kg, suggesting ZC88 relieved allodynic response of neuropathic pain. When concurrently administered with morphine, ZC88 (20-80 mg/kg) dose-dependently potentiated morphine analgesia and attenuated morphine analgesic tolerance in hot-plate tests. ZC88 also prevented chronic exposure to morphine-induced physical dependence and withdrawal, but not morphine-induced psychological dependence in conditioned place preference model. These results suggested that ZC88, a new non-peptide N-type calcium channel blocker, had notable oral analgesia and anti-allodynia for acute and neuropathic pain. ZC88 might be used in pain relief by either application alone or in combination with opioids because it enhanced morphine analgesia while prevented morphine-induced tolerance and physical dependence.     

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.     

当归注射液的镇痛作用

目的:研究当归注射液的镇痛作用.方法:采用小鼠扭体法、小鼠热板法、大鼠电刺激鼠尾法进行镇痛实验.结果:当归注射液可显著抑制醋酸所致小鼠扭体反应,作用强度呈剂量依赖性,且可提高热板法所致小鼠痛觉反应的痛阈及大鼠电刺激法所致的痛阈,其强度与阿司匹林相当.结论:当归注射液具有镇痛作用.     

仙鹤草提取物镇痛抗炎试验的实验研究

目的:初步探讨中药仙鹤草提取物的镇痛抗炎作用.方法:取仙鹤草的水提取物和乙醇提取物,应用醋酸致小鼠扭体法、小鼠热板法、二甲苯致小鼠耳廓肿胀法和大鼠角叉菜胶足跖肿胀法研究其镇痛抗炎作用.结果:仙鹤草乙醇提取物和水提起物可减少醋酸致小鼠扭体次数,延长小鼠舔足时间,减轻二甲苯致小鼠耳廓肿胀程度,减小角叉菜胶致足跖肿胀程度;乙醇提取物作用强于水提取物.结论:中药仙鹤草乙醇提取物具有明显的镇痛抗炎作用.     

Antinociceptive activity of intracisternally and intrathecally administered eptazocine, a novel analgesic, in mice

Antinociceptive potency of eptazocine (1-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-ben zazonine), a novel analgesic derived from homobenzomorphan, was compared with that of morphine and pentazocine after intracisternal and intrathecal administration into conscious mice using acetic acid-induced writhing, tail pressure and hot plate tests. The rank order of potency for inhibition of writhing after intracisternal administration was morphine greater than eptazocine greater than pentazocine. In contrast, the intrathecal compounds inhibited writhing with a rank order of potency of eptazocine greater than or equal to morphine greater than pentazocine. On the tail pressure and hot plate tests after intrathecal administration, ED50 ratios of eptazocine to morphine were much smaller than that on the writhing test. Systemic naloxone did not antagonize the antinociceptive effect of intrathecal eptazocine on the writhing test. These results suggest that the antinociceptive action of eptazocine is rather specific to chemical nociceptive stimuli and may be mediated via spinal non mu-opioid receptors in the mouse.