国产降纤酶治疗急性脑梗死60例分析

目的　观察国产降纤酶对急性脑梗死临床疗效和纤维蛋白原下降情况 ,进一步验证注射用降纤酶治疗急性脑梗死的有效性和安全性。　方法　选择 1 998年 2月至 1 2月发病 1天内急性脑梗死住院病人6 0例。用随机双盲对照的临床研究 ,揭盲 4 0例 ,分为治疗组 ( 2 4例 )和对照组 ( 1 6例 ) ,均在起病后 2 4 h内给药 ,首剂 1 0 u降纤酶冻干剂加入 2 5 0 ml生理盐水中静脉点滴 ,在 2～ 3h内滴完 ,其后 5 u隔日 1次静滴 ,共连用 3次 ,总剂量 2 0 u。观察期间合并给予低分子右旋糖酐 5 0 0 ml,或灯盏花注射液 4 0 ml静脉点滴 ,连续用药 1 4天。按全国第四界脑血管病学术会议通过的评分标准 ,分别对治疗前 ,治疗后 1 4天的疗效和生活状态进行评定和评估。　结果　治疗前后神经功能评分 :治疗组 :治疗前 1 2 .3± 9.75 ,治疗后 1 4天为 5 .93± 7.6 0 ,治疗前后统计学有极显著性差异 ( P <0 .0 1 ) ,治疗 1 4天总有效率 92 % ;对照组 :治疗前为 1 4.6± 1 0 .6 ,治疗后 1 4天为 6 .4 6± 8.6 5 ,治疗前后统计学有显著性差异 ( P <0 .0 5 ) ,治疗后 1 4天总有效率 6 2 %。血液学指标 :治疗组 FIB含量治疗后较治疗前明显下降 ( P <0 .0 0 1 ) ;对照组治疗前后无明显变化 ( P >0 .1 0 )。治疗组 PT用药后第 2、6天均较用     

二氧化硫吸入对小鼠脑组织的氧化损伤

对昆明小鼠进行不同浓度SO2 吸入试验 ,然后测定脑组织中还原型谷胱甘肽 (GSH)含量、谷胱甘肽过氧化物酶 (GSH Px)活性、超氧化物歧化酶 (SOD)活性及脂质过氧化产物丙二醛 (MDA)含量 ,研究SO2 对小鼠中枢神经系统的氧化损伤作用 .雄鼠脑组织匀浆上清液GSH含量在SO2 浓度为 14mg m3 时明显上升 (P <0 0 5 ) ,浓度为 2 8、5 6和 84mg m3 时极显著降低 (P <0 0 1) ,而雌鼠在14和 2 8mg m3 时无明显变化 (P >0 0 5 ) ,在 5 6和 84mg m3 时极显著降低 (P <0 0 1) .雌雄小鼠的GSH Px活性在 14和 2 8mg m3 时无明显变化 (P >0 0 5 ) ,在 5 6、84mg m3 时均极显著降低 (P <0 0 1,P <0 0 0 1) .在SO2 上述 4种吸入浓度下 ,雌雄小鼠的SOD活性均显著降低 (P <0 0 5 )或极显著降低 (P <0 0 1,P <0 0 0 1) ;雄鼠和雌鼠的脂质过氧化产物丙二醛 (MDA)含量均极显著增高 (P <0 0 1,P <0 0 0 1) .结果表明 ,小鼠脑组织对SO2 的氧化损伤作用非常敏感 ,是SO2 的靶器官之一 ,SO2 的污染可能与某些脑疾患有关     

磁处理白术药液对小白鼠免疫器官指数影响的药效研究

目的 :从免疫学方面探讨磁处理白术药液对小白鼠免疫器官指数影响的药效作用。方法 :用不同强度的磁处理白术药液及非磁处理白术药液对小白鼠进行腹腔注射 ,连续 7d ,每天一次 ,末次给药 1 2h后处死 ,称其体重 ,取出胸腺、脾脏及肝脏 ,称重 ,计算各器官指数。结果 :与正常对照组比较 ,磁处理白术药液组对小白鼠的肝脏指数、脾脏指数均有极显著的提高 (P <0 .0 1 ) ,胸腺指数也有影响 ,但差异不显著 (P>0 .0 5 ) ;与非磁处理药液组比较 ,磁处理药液组对小白鼠的肝脏指数、脾脏指数、胸腺指数有影响 ,但差异不显著 (P >0 .0 5 )。结论 :磁处理白术药液对免疫器官指数有明显作用     

降纤酶治疗脑梗死的临床观察

目的　观察国产降纤酶治疗脑梗死的临床疗效、毒副作用以及对血浆纤维蛋白原、凝血酶原时间的影响。　方法　对 CT或 MRI确诊的脑梗死病人 33例 ,按随机方法分为治疗组与对照组 ,分别于治疗前后测定神经功能缺损评分、纤维蛋白原、凝血酶原时间及肝、肾功能并进行对比分析。　结果　降纤酶治疗后神经功能缺损明显改善 ( P <0 .0 0 1 )并且治疗后 1天即出现明显效果 ( P <0 .0 0 5 ) ,总有效率明显高于对照组 ( P <0 .0 5 ) ;血浆纤维蛋白原明显下降 ,与对照组相比 P <0 .0 5 ;治疗过程中未见不良反应。　结论　降纤酶治疗脑梗死疗效显著 ,起效快 ,较安全。     

红景天对心肌梗死大鼠缺血心肌血管新生作用及对VEGF的影响

目的:探讨中药红景天对急性心肌梗死大鼠缺血心肌血管新生作用及其对血管内皮生长因子(EGF)蛋白和mRNA表达的影响.方法:52只SD大鼠随机分成单纯手术组、术后给药组、提前给药组、假手术组和正常对照组.采用开胸结扎冠状动脉左前降支的方法建立心肌梗死模型,4周后处死动物.Ⅷ因子免疫组化染色后对各组大鼠梗死边缘区微血管进行计数;免疫组化技术及Western blot技术检测各组缺血心肌VEGF蛋白质水平表达变化;逆转录多聚酶链反应(RT-PCR)法检测缺血心肌VEGF mR-NA表达变化.结果:术后给药组和提前给药组血管计数均较单纯手术组增多(P＜0.01),且提前给药组明显多于术后给药组(P＜0.01);术后给药组和提前给药组缺血心肌VEGF及其mRNA表达较单纯手术组增加(P＜0.01),提前给药组缺血心肌VEGF及其mRNA表达明显高于术后给药组(P＜0.01).结论:红景天能够促进心梗后大鼠缺血心肌血管新生,其作用机制可能与上调局部心肌VEGF及其mRNA表达有关.预给红景天可能增强对心梗大鼠的上述作用.     

中枢注射Nesfatin-1与Exendin(9-39)对大鼠摄食和胃肠动力调节的影响

目的:探讨下丘脑室旁核注射GLP-1R拮抗剂Exendin(9-39)对Nesfatin-1所致大鼠摄食和胃肠动力改变的影响及作用机制。方法:选择40只雄性Wistar大鼠,随机分成正常对照组(NC组)、Nesfatin-1组(NS组)、Exendin(9-39)组(ES组)、Nesfatin-1联合Exendin(9-39)组(NE组)。采用下丘脑室旁核(PVN)埋置套管并分别给予以上药物干预,干预前和干预后的12小时、24小时记录和比较各组大鼠的摄食、饮水及体重变化。2天后,采用甲基纤维素-酚红溶液灌胃法测各组大鼠胃排空率,实时荧光定量法(RT-PCR)检测下丘脑及胃组织GLP-1Rm RNA的表达。结果:与基础摄食量比较,NS组大鼠给药后12 h、24 h的摄食量减少(P0.05),NE组大鼠给药后12 h、24 h的摄食量减少(P0.05),但较NS组增加(P0.05);与基础饮水量比较,NS组、NE组给药后12 h饮水量减少(P0.05);与基础体重比较,NS组大鼠给药后12 h、24 h的体重降低(P0.05),NE组大鼠给药后12 h的体重降低(P0.05),但较NS组增加(P0.05);NS组大鼠给药后胃排空率较NC、NE组大鼠显著下降(P0.05),NS组大鼠下丘脑GLP-1Rm RNA的表达量较NC组增加(P0.05)。结论:中枢给予GLP-1R拮抗剂能减弱Nesfatin-1引起的摄食抑制、胃排空延迟及体重下降效应,Nesfatin-1可能通过与GLP-1的协同作用参与摄食及胃肠动力的调节。     

炎性条件对于辣椒素镇痛作用的影响

目的：观察辣椒素的镇痛时间是否在炎性条件下发生改变,以及辣椒素在产生镇痛作用前的痛觉过敏时间是否受炎性条件的影响。方法：健康成年昆明雌性小鼠50只,（实验前对其测定热缩足反射潜伏期,作为基础值）,随机分为五组（n=10）,：生理盐水组,辣椒素赋形剂实验一组（吐温80：95％乙醇：生理盐水=1：1：8配置）,0．5％辣椒素实验二纽（C0．5）,剩余小鼠用完全性弗氏佐剂建立炎性模型,将建模成功的小鼠随机分为辣椒素赋形剂实验三组,0．5％辣椒素实验四组。各组小鼠均采用右后足给药,0．05ml。观察给药后1,4,7小时后小鼠的热缩足反射潜伏期时间,以及热缩足反射潜伏期恢复至正常范围所需时间。结果：1．五组小鼠的热缩足反射潜伏期的比较：五组小鼠的基础值差别无统计学意义（P〉0．05）。生理盐水组与辣椒素赋形剂实验一组相比较,差别无统计学意义（P〉0．05）。2．实验二组热缩足潜伏期时间在注药后7小时内小于生理盐水组（P〈0．05）,注药后第2-5天大于生理盐水组（P〈0．05）,第三天效果最强,作用最明显,第六天恢复至基础值。3．实验三组热缩足潜伏期时间小于生理盐水组（P〈0．05）,注药后第18．20天恢复至基础值。4．实验四组热缩足潜伏期时间在注药后4小时内小于生理盐水组（P〈0．05）,注药后4小时后大于生理盐水组（P〈0．05）,注药后第18—19天恢复至基础值,注药后第二,三天效果最强,作用最明显,以后作用逐渐减退但仍高于基础值。结论：辣椒素的镇痛时间在炎性条件下延长,而且延长的时间与炎性条件持续的时间保持一致。辣椒素在产生镇痛作用前的痛觉过敏时间在炎性条件下缩短。     

戊乙奎醚与咪唑安定作为妇科腹腔镜手术麻醉前用药对患者血流动力学的影响

目的:戊乙奎醚与咪唑安定作为妇科腹腔镜手术麻醉前用药对患者血流动力学的影响.方法:将150例美国麻醉师协会(ASA)分级Ⅰ～Ⅱ级妇科腹腔镜手术患者(病种包括子宫肌瘤、宫外孕、单纯卵巢囊肿)随机分为2组,每组75例.于麻醉诱导前10分钟分别静注戊乙奎醚0.01 mg/kg (A组)、咪唑安定0.01 mg/kg (B组).记录并比较注药后5分钟,10分钟,20分钟患者口干程度的视觉模拟评分(visual analogue scale,VAS);记录并比较患者注药前10分钟(P1)、注药后10分钟(P2)、患者意识消失时(P3)、手术开始时(P4)、手术开始后1小时(P5)、手术结束时(P6)、苏醒后1小时(P7)时的脉搏血氧饱和度(SpO2)、心率(HR)、收缩压(SBP)、舒张压(DBP);记录并比较术后气管及口腔内分泌物量、动脉血乳酸(ABL)含量.结果:对两组患者于麻醉诱导前分别注射0.01 mg/kg戊乙奎醚和0.01 mg/kg咪唑安定,结果显示B组患者在给药后5分钟,10分钟,20分钟心率较A组相同时间点心率有显著升高(P＜0.05),口干程度VAS评分B组显著高于A组.手术期间两组血液动力学变化为B组注药后血压、心率均较基础值显著降低(P＜0.05);两组患者注药前后脉搏氧饱和度均无显著变化(P＞0.05).B组气管及口鼻腔分泌物的量明显多于A组,且术后测定动脉血乳酸含量B组显著高于A组(P＜0.05).结论:于麻醉诱导前20分钟静注戊乙奎醚0.01 mg/kg可以有效减少患者术中及术后口腔、呼吸道分泌物,而不致心率增加和血压升高,对患者血流动力学无显著影响;对患者微循环有明显改善作用.     

磁处理党参药液对小鼠肠推进运动影响的药效研究

目的 :观察磁处理党参药液对小鼠肠推进运动的影响。方法 :实验分为非磁处理党参药液对照组 ,生理盐水对照组 ,0 .1T磁处理试验组和 0 .2 5T磁处理药液试验组 ,采用灌胃给药的途径进行实验观察。结果 :0 .1T和 0 .2 5T磁处理药液组和生理盐水对照组相比较 ,试验组具有显著促进小鼠肠的炭末推进作用 (p <0 .0 1 ) ;非磁处理与磁处理党参药液组相比较 ,0 .1T和 0 .2 5T磁处理药液组对小肠的炭末推进率有着显著的抑制作用 (p <0 .0 1 )。结论 :党参磁处理药液对小鼠肠的推进有明显作用。     

β-乳香酸对血瘀证大鼠血液流变学和血管内皮功能的影响

目的:研究β-乳香酸(β-BA)对血瘀证大鼠血液流变学和血管内皮功能的影响。方法:24只SD大鼠随机分为4组:空白对照组、模型组、低剂量β-BA(100 mg/kg)组、高剂量β-BA(200 mg/kg)组,每组6只,每12小时给药1次、连续给药7次,第5次给药后,除空白组大鼠外,给予皮下注射盐酸肾上腺素(0.8 mg/kg)2次,间隔4小时,中间给予冰水(0-2℃)刺激5分钟造成大鼠急性血瘀证模型。最后一次给药30分钟内腹主动脉取血检测不同切变率下的全血粘度(WBV)、凝血指标、血浆内皮素-1(ET-1)、一氧化氮(NO)浓度,并取颈动脉观察病理变化。结果:与空白对照组相比,模型组全血粘度明显升高(P0.01),凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)显著缩短(P0.01),纤维蛋白原(FIB)含量增加(P0.01),血浆ET-1水平升高,血浆NO含量降低(P0.01)。与模型组相比,β-BA组全血粘度明显降低,TT、APTT、PT显著延长(P0.01),纤维蛋白原含量减少(P0.01),血浆ET-1水平降低,血浆NO水平升高(P0.01)。结论:β-乳香酸能显著改善血瘀证大鼠血液流变学异常,并保护其血管内皮功能。     

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room.For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief.     

Patient-controlled and analgesia with ketorolac in pediatric surgery

Our aim was to quantify the analgesic efficiency of the patient-controlled analgesia technique (PCA), using ketorolac, in children aged 6–14 undergoing a surgical intervention. We carried out a double-blind test with two randomly selected groups: the PCA group comprising patients submitted to intravenous PCA, with “bolus on demand” and the Standard group, with conventional analgesia dispensed with ketorolac I.V. (0.5 mg/kg/6 hours). Evaluation of pain experienced was performed using the Hannallah behavioural scale and quantification of the summing of pain intensity. Analgesic efficiency was determined by the pain intensity difference (PID) score. Evaluation of pain experienced during hour 1 reveals a marked reduction with time for each group; no inter-group differences were found. At hour 6 there were neither intra-group nor inter-group differences. The accumulated pain score revealed a significant reduction in hour 6, with no differences between the two groups. Evaluation of the analgesic effect revealed no differences, either intra-group or intergroup, during the experimental period. The sum of the PIDs revealed significant differences in the standard group between the values for hours 1 and 6. Under the experimental conditions described, both techniques were equally effective for pain treatment, but the efficiency was higher for the PCA group.     

Patient-controlled analgesia with ketorolac in pediatric surgery

Our aim was to quantify the analgesic efficiency of the patient-controlled analgesia technique (PCA), using ketorolac, in children aged 6-14 undergoing a surgical intervention. We carried out a double-blind test with two randomly selected groups: the PCA group comprising patients submitted to intravenous PCA, with "bolus on demand" and the Standard group, with conventional analgesia dispensed with ketorolac I.V. (0.5 mg/kg/6 hours). Evaluation of pain experienced was performed using the Hannallah behavioural scale and quantification of the summing of pain intensity. Analgesic efficiency was determined by the pain intensity difference (PID) score. Evaluation of pain experienced during hour 1 reveals a marked reduction with time for each group; no inter-group differences were found. At hour 6 there were neither intra-group nor inter-group differences. The accumulated pain score revealed a significant reduction in hour 6, with no differences between the two groups. Evaluation of the analgesic effect revealed no differences, either intra-group or intergroup, during the experimental period. The sum of the PIDs revealed significant differences in the standard group between the values for hours 1 and 6. Under the experimental conditions described, both techniques were equally effective for pain treatment, but the efficiency was higher for the PCA group.     

克班宁的镇痛作用部位及作用机制探讨

以探究克班宁的镇痛作用部位并初步明确其镇痛机制为目的。采用小鼠足趾注射甲醛法、热板法及腹腔注射醋酸(扭体法)所致疼痛模型,探讨克班宁的镇痛作用;以小鼠输精管经壁电刺激法,了解克班宁对吗啡受体的影响。结果发现克班宁在3.2 mg/kg时对三种疼痛模型均显示明显的抑制作用,并能明显抑制小鼠输精管经壁电刺激所引起的收缩,且该收缩不能被纳络酮所拮抗。因此,克班宁可能具有中枢样镇痛作用,但作用机制与吗啡受体无关。     

白芷乙醇提取物镇痛作用研究

目的:观察白芷乙醇提取物(EEAD)的镇痛作用。方法:各组小鼠连续灌胃不同剂量的白芷乙醇提取物3d,末次给药后1 h。以热板致痛法、醋酸扭体法为疼痛模型,生理盐水为阴性对照药,阿司匹林为阳性对照药,考察白芷乙醇提取物的镇痛作用。结果:白芷提取物可显著延长小鼠热板反应的潜伏期,及扭体反应出现的时间。结论:白芷乙醇提取物镇痛作用明确。     

中药止痛贴与吗啡联合应用于癌症疼痛的镇痛效果及安全性

目的:探讨中药止痛贴与吗啡联合应用于癌症疼痛治疗中的镇痛效果及安全性。方法:选取2016年5月至2017年5月我院收治的100例中重度癌症疼痛患者为研究对象,根据随机数字表方法将入选的患者分为对照组和研究组,每组50例。对照组患者给予吗啡治疗,研究组患者在此基础上联合应用中药止痛贴治疗,连续给药14天。比较两组患者的临床疗效、数字评分法(digital scoring method,NRS)、爆发痛次数、吗啡使用量、中医证候评分。结果:研究组患者治疗总有效率为96.0%,显著高于对照组患者(86.0%,P0.05)。研究组盐酸吗啡缓释片使用剂量[(83.23±23.14)mg/d]低于对照组[(110.13±25.23)mg/d](P0.05)。治疗前,两组患者各中医证候评分比较差异均无统计学意义(P0.05);治疗后,两组患者各中医证候评分均较治疗前明显降低,且研究组显著低于对照组,差异有统计学意义(P0.05)。研究组患者的NRS评分、爆发痛次数显著低于对照组(P0.05),两组患者均未见严重的不良反应。结论:中药止痛贴与吗啡联合应用于癌症疼痛的可有效提高镇痛效果,改善患者的中医证候,减少吗啡使用量,且安全性高。     

NAAG Peptidase Inhibition in the Periaqueductal Gray and Rostral Ventromedial Medulla Reduces Flinching in the Formalin Model of Inflammation

ABSTRACT: BACKGROUND: Metabotropic glutamate receptors (mGluRs) have been identified as significant analgesic targets. Systemic treatments with inhibitors of the enzymes that inactivate the peptide transmitter N-acetylaspartylglutamate (NAAG), an mGluR3 agonist, have an analgesia-like effect in rat models of inflammatory and neuropathic pain. The goal of this study was to begin defining locations within the central pain pathway at which NAAG activation of its receptor mediates this effect. RESULTS: NAAG immunoreactivity was found in neurons in two brain regions that mediate nociceptive processing, the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). Microinjection of the NAAG peptidase inhibitor ZJ43 into the PAG contralateral, but not ipsilateral, to the formalin injected footpad reduced the rapid and slow phases of the nociceptive response in a dose-dependent manner. ZJ43 injected into the RVM also reduced the rapid and slow phase of the response. The group II mGluR antagonist LY341495 blocked these effects of ZJ43 on the PAG and RVM. NAAG peptidase inhibition in the PAG and RVM did not affect the thermal withdrawal response in the hot plate test. Footpad inflammation also induced a significant increase in glutamate release in the PAG. Systemic injection of ZJ43 increased NAAG levels in the PAG and RVM and blocked the inflammation-induced increase in glutamate release in the PAG. CONCLUSION: These data demonstrate a behavioral and neurochemical role for NAAG in the PAG and RVM in regulating the spinal motor response to inflammation and that NAAG peptidase inhibition has potential as an approach to treating inflammatory pain via either the ascending (PAG) and/or the descending pain pathways (PAG and RVM) that warrants further study.     

Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice

The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and Radix Cynanchi Paniculati have been reported in recent years. A new formula named Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at 9:7:7 ratio according to traditional Chinese theories. The present study aims to evaluate the effect of JYQP as a novel painkiller in various models. Acute toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced writhing, hot plate test, formalin test, and naloxone-pretreated writhing test were employed to elaborate the analgesic activity of JYQP and its possible mechanism. A bone cancer pain mouse model was performed to further assess the effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal symptoms was conduct to examine the physical dependence of mice on JYQP. Data revealed that JYQP reduced writhing and stretching induced by acetic acid; however, this effect could not be blocked by naloxone. JYQP specifically suppressed the phase II reaction time in formalin-treated mice; meanwhile, no analgesic effect of JYQP in hot plate test was observed, indicating that JYQP exerts analgesic activity against inflammatory pain rather than neurogenic pain. Furthermore, JYQP could successfully relieve bone cancer pain in mice. No physical dependence could be observed upon long-term administration in mice. Collectively, our present results provide experimental evidence in supporting clinical use of JYQP as an effective and safe agent for pain treatment.     

Analgesic and anti-inflammatory effects of the amphibian neurotoxin, anntoxin

Anntoxin is the first gene-encoded neurotoxin identified from amphibians, which is a 60-residue neurotoxin peptide, acting as an inhibitor of tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC). Sodium channels have been considered as therapeutic targets for pain. Several animal models of persistent inflammatory and neuropathic pain (tail-flick test, hot plate test, acetic acid-induced writhing test, formalin-induced paw licking, carrageenan-induced paw edema) were used to test analgesic functions of recombinant anntoxin (r-anntoxin). In all these animal models, r-anntoxin showed strong analgesic functions. R-anntoxin obviously inhibited secretions of both tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2). Histopathological study indicated that r-anntoxin reduced the edematous epidermis induced by carrageenan. All these results indicate that r-anntoxin has strong analgesic and anti-inflammatory activities.     

Potentiation of analgesia and reversal of tolerance to morphine by calcium channel blockers

Effect of four calcium channel blockers (CCBs) belonging to different chemical classes, alone and in combination with morphine was investigated on two models of pain sensitivity, i.e. formalin and tail flick tests in mice. All the studied CCBs, i.e. diltiazem, flunarizine, nimodipine and verapamil inhibited formalin-induced pain responses; however, with verapamil, though there was a trend towards a reduction of paw-licking response to formalin, it was not found to be statistically significant. In contrast, none of the CCBs affected the tail flick latency at any of the doses studied. Morphine, a mu-receptor agonist exerted a significant analgesic effect in formalin as well in tail flick tests. Pretreatment with all CCBs significantly enhanced the analgesic effect of morphine in both tests of nociception. Further, concomitant administration of one of the CCBs, diltiazem with morphine prevented the development of tolerance to the latter. However, combination of diltiazem with morphine, like morphine alone was found to be ineffective in morphine tolerant animals. Results, thus, show that CCBs produced an analgesic effect of their own in formalin-induced tonic pain and potentiated the analgesic activity of morphine. They also modulated opioid-induced tolerance.