Calcium channel modulation by dihydropyridines modifies sufentanil-induced antinociception in acute and tolerant conditions

Summary The study was aimed at elucidating the possible participation of l-type Ca²⁺ channel in the acute analgesic effect of an opiate and the development of tolerance to this action. Sufentanil, a selective p agonist, and two dihydropyridines, the Ca²⁺ antagonist nimodipine and the Ca²⁺ agonist Bay K 8644, were selected. The tail-flick test was used to assess the nociceptive threshold. In naive rats, nimodipine (200 g/kg) potentiated the analgesic effect of sufentanil reducing the ED₅₀ from 0.26 to 0.08 g/kg. Similar results were observed with its (–)-enantiomer Bay N 5248, while the (+) enantiomer Bay N 5247 was ineffective. Tolerance to the opiate was induced by chronic subcutaneous administration of sufentanil with minipumps (2 g/h, 7 days). In these conditions the dose-response curve to sufentanil was displaced to the right and the ED₅₀ was increased to 1.49 g/kg. In tolerant rats, nimodipine preserved its potentiating ability and prevented the displacement to the right of the sufentanil dose response-curve (ED₅₀ = 0.48 g/kg). When nimodipine was pumped (1 g/h, 7 days) concurrently with sufentanil, the development of tolerance to the opioid was not disturbed. However, the expression of tolerance was abolished and even the effect of acutely administered sufentanil was markedly potentiated (ED₅₀ = 0.03 g/kg). Similar experiments were performed with Bay K 8644. In naive rats, Bay K 8644 at a low dose (20 g/kg) that behaves as a calcium agonist, antagonized the analgesic effect of sufentanil (ED₅₀ = 0.58 g/kg), whereas at a high dose (200 g/kg) it potentiated this action (ED₅₀ = 0.15 g/kg). In tolerant rats, Bay K 8644 (20 g/kg) preserved its antagonizing ability inducing a displacement to the right of the sufentanildose-response curve (ED₅₀ = 4.2 g/kg). When Bay K 8644 was pumped (1 g/h, 7 days) concurrently with sufentanil, it enhanced the expression of tolerance to the opiate (ED₅₀ = 3.8 g/kg). These results suggest that the calcium fluxes through the l-type channel in neurones are functionally linked to the activation of the opiate receptor: the blockade of the channel increased the potency of sufentanil, whereas its activation reduced the potency of the opiate. In chronic experiments, DHPs concurrently administered with sufentanil did not affect the development of tolerance to the opiate. However, nimodipine prevented the expression of this phenomenon. Even more, the animals became hypersensitive to the opiate suggesting that the adaptative mechanisms induced by chronic opiate could be affected by chronic nimodipine.This work was supported by grants from Universidad de Cantabria-Caja Cantabria (1988) and Bayer AG, Wuppertal, FRGPredoctoral Fellow: Fondo de Investigaciones Sanitarias de la Seguridad Social.Send offprint requests to: M. A. Hurlé at the above address     

梅笠草提取物的抗炎及镇痛作用

[目的 ]探讨梅笠草提取物的抗炎及镇痛作用 .[方法 ]采用巴豆油所致小鼠耳壳肿胀的方法 ,测定耳片的肿胀度 ;用冰醋酸所致小鼠的扭体次数 ,测定小鼠的扭体反应次数 .[结果 ]梅笠草对巴豆油所致小鼠耳壳肿胀有抑制作用 ,与对照组相比有显著性差异 ;同时能减少冰醋酸所致小鼠的扭体次数 ,与对照组相比有显著性差异 .[结论 ]梅笠草提取物具有一定的抗急性炎症和抗镇痛作用     

2.5g/L罗哌卡因高位硬膜外阻滞对呼吸功能的影响

目的 观察2.5g/L罗哌卡因用于上胸段硬膜外阻滞时对呼吸功能的影响。方法 20例行择期乳癌改良根治术患者,于T3－4硬膜外腔注入2.5g/L罗哌卡因10－15ml,观察用药前及用药后10、15、30min4个时点的呼吸功能变化,同时监测麻醉平面和循环功能。结果 硬膜外腔注入2.5g/L罗哌卡因后10、15、30min与麻醉前相比,潮气量、补呼气量和肺活量明显降低（P＜0．05－0．01）,呼吸频率增快（P＜0．05）,分钟通气量与SpO2保持不变（P＞0．05）。胸部皮肤痛觉消失平面T1－2－T6－7,循环功能（HR、ECG、MAP、SBP、DBP）稳定。麻醉期间无其它不良反应。结论 2.5g/L罗哌卡因用于高位硬膜外阻滞,在获得满意镇痛范围及循环功能稳定的同时,肺通气功能基本保持不变。     

腰椎间盘突出连续硬膜外阻滞疗效观察

目的：探讨连续硬膜外阻滞治疗腰椎间盘突出的适应证和疗效相关因素。方法：经腰(骶)部穿刺,1％利多卡因连续硬膜外腔阻滞法。结果：随访151例,随访8～31个月,优良83例(55．0％),疼痛明显改善,以中央型和腰痛为主的椎间盘突出较为有效。结论：本封闭法疗效与椎问盘突出部位、类型有关,可适用于疼痛严重的椎间盘突出。     

硬膜外麻醉中用异丙酚镇静目标控制输注系统的性能及测评

目的：研究硬膜外阻滞时异丙酚目标控制输注镇静系统的性能。方法：12例中、低位硬膜外腔阻滞择期手术病人,选用Marsh的药代动力学参数进行异丙酚目标控制输注镇静。目标血药浓度设定范围1．5－3．0mg.L^-1,由麻醉医师根据镇静需要调整目标浓度,笨一病例的目标浓度可调整1－2次,以高效液相色谱法检测异丙酚血药浓度。计算偏离不性、不准确度等性能评价指标,分析系统性能。结果：多数实测血药浓度低于预计浓度,偏离性（MDPE）为－16．14％。偏离性和不准确确度与硬膜外阻滞范围无相关。结论：采用Marsh参数作目标控制镇静,血浆异丙酚目标浓度与实测浓度的偏离性较大,应用时需进行校正。     

大鼠中枢内源性镇痛系统内GABAB受体的分布

目的：观察α－氨基丁酸B受体（GABAR）在大鼠中枢内源性镇痛系统内的定位分布,方法：GABABR特异性抗体的免疫组织化学染色方法：结果：GABABR样阳性胞体较密集地分布于中缝核簇的核团,如中缝背核,中缝正中核,中缝桥核,中缝大核,中缝苍白核,中缝隐核,此外,中脑导水管周围灰质和巨细胞网状核α部内也有GABAR样阳性胞体,上述核团内亦可见GABABR样阳性纤维和终末,结论：中枢内源性镇痛系统内有GABABR样阳性胞体,纤维及终末,这些阳性结构可能与对该系统的调控有关。     

老年人低位硬膜外麻醉围术期自主神经功能的变化

目的：应用心率变异性（HRV）分析仪监测评估低位硬膜外麻醉围术期自主神经的改变。方法：选择低位硬膜外麻醉下择期手术患者20例,ASAⅠ-Ⅱ级,按年龄分为老年组和年轻组,每组10例,观察术前1d、麻醉完善后切皮前、切皮后30min、术后2h,1d,3d,7d处时相点的心率（HR）、平均动脉压（MAP）以及HRV分析各成分变化。结果：围术期老年组HRV显示RMSSD（相邻RR间期差值均方根）、总频（TP）、低频（LF）、代频标化（LFnorm)均呈显著性下降,同时伴有心率减慢、平均动脉下降。年轻组TP和LF在麻醉完善后切皮前、术后2h,1d下降显著,于术后3d恢复,而R和MAP在围术期无显著改变。两组两比较,老年组TP和LF在麻醉后各时相占 明显低于年轻组（P＜0．01）。老年组高频（HF）及高频标化（HFnorm)在麻醉给药后切皮瓣均无明显变化,但在术中和术后各时相点的下降,而年轻组仅切皮后30min,出现一过性下降。结论HRV可较好地评估围术期机体自神经变化;术期麻醉和手术创伤均可使机体自主神系统调节受损,尤其老年人受损程度大,恢复慢,恢复慢,术后1周仍不能完全恢复。     

穴位体表电刺激对术后PCEA的强化效应

目的　观察穴位体表电刺激对术后患者硬膜外自控镇痛（PCEA）效果、镇痛药用量、血清皮质醇浓度和不良反应的影响。方法　 选择经腹全宫切除术患者40例（ASAⅠ～Ⅱ级）,随机分成二组,每组20例。A组：于术后第4,8小时 Han's各刺激30 min,术后行PCEA。B组：单纯行术后PCEA（对照组）。术后随访镇痛效果、镇静评分、布氏舒适评分（BCS）,分段记录24 h镇痛药用量及总按压次数/实进次数（D1/D2）比值,血清皮质醇含量,肛门恢复排气时间和不良反应情况。结果　两组镇痛效果满意,A组BCS评分高于B组（P＜0.05）。A组镇痛药用量为（31.7±1.9）ml,与对照组（34.2±2.1）ml相比差异有显著性（P＜0.01）。血清皮质醇浓度两组均较术前下降,但A组术后8 h的下降幅度大于对照组。A组恢复肛门排气时间快于B组,而且恶心、呕吐与对照组相比有所减少。结论　术后患者硬膜外腔自控镇痛（PCEA）复合应用穴位体表电刺激,可增强镇痛效果,减少用药量,降低不良反应,是安全有效的复合镇痛方法。     

全麻诱导前预注芬太尼“先发镇痛”效应临床研究

目的：探讨全麻预注芬太尼的先发镇痛效应。／方法：选择40例择期全麻病人,随机分成试验组与对照组（n=20例）,术前常规用药,试验组诱导前用芬太尼5ug/kg,对照组将芬太尼改切皮后静注,术中麻醉维持相同,手术结束后病人自然清醒。术后有镇痛药使用意愿者均使用哌替啶镇痛。结果：两组病人一般情况及芬太尼总用量无显著性差异（P＞0．05）,试验组初次使用镇痛药时间明显延长（P＜0．01）,用药次数及剂量也显著少于对照组（P＜0．01）,试验组术后仅7（35％）例使用派替啶,而对照组使用哌替啶者达15（75％）例,两组差异性显著（P＜0．05）,结论：全麻前预注芬太尼具有良好的先发镇痛效应。     

硬膜外阻滞复合全身麻醉用于慢性阻塞性肺病病人的临床效果

目的比较硬膜外阻滞复合全身麻醉或单纯全身麻醉对上腹部和胸腔内手术病人术后肺功能和肺部并发症的影响。方法24名伴有中度术后肺部并发症危险的慢阻肺病人,接受上腹部或胸腔内手术,随机分成单纯全身麻醉(GA组)和硬膜外阻滞复合全身麻醉(Epi-Ga组)两组。术后采用VRS法评定镇痛效果。根据临床症状和体征、X线胸片、血气分析和床旁肺功能测定评估是否发生肺部并发症。术前1d和术后3d内评估和记录上述指标。结果术毕,GA组病人平均(34±16)min苏醒,(67±22)min拔除气管导管;Epi-Ga组苏醒时间和拔管时间分别为(12±4)和(32±12)min。术后第1天和第2天,Epi-Ga组病人术后镇痛效果明显优于GA组(P<0.01)。术后第1天,Epi-Ga组病人的FVC、FEV1/FVC%和FEF25%-75%下降不如GA组显著(P<0.05)。GA组有4例需要纤维支气管镜协助吸痰,而Epi-Ga组则无一例需要。两组病人术后肺炎、肺不张、支气管痉挛和呼吸衰竭的发生率无显著差异。结论局麻药加阿片类药物硬膜外自控镇痛使病人术后更加舒适,且能够改善病人术后肺功能。尽管两组病人术后肺部并发症无明显差异,但硬膜外阻滞复合全身麻醉以及术后硬膜外自控镇痛确实能够方便慢阻肺病人的术后管理。