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     

Optimum dose of epidural morphine for postsurgical analgesia

To determine the optimum dose of epidural morphine for postoperative pain control, 0.5–4.0mg of morphine was administered to 198 patients who had undergone operations on lower abdomen or lower extremities under continuous epidural anesthesia. Analgesic effect of morphine and incidence of nausea or vomiting were studied using linear discriminant analysis. As explanatory variables, age and dose of morphine were statistically significant in discriminating analgesic effect of morphine. Among indices for physique of patients, height was the most useful for predicting the analgesic effect. The dose which made the discriminant function zero corresponded to the minimum effective dose (MED) of morphine and it was expressed as follows; MED (mg·meter^–1) = –0.0107 × age + 1.85. Predicting the incidence of nausea or vomiting in relation to the dose of morphine did not reach a level of statistical significance.(Ochi G, Yamane C, Arai T: Optimum dose of epidural morphine for postsurgical analgesia. J Anesth 4: 35–39, 1990)     

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     

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。     

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。     

子宫峡部阻滞麻醉应用于人工流产术的临床观察

目的　探讨人工流产术中最佳的镇痛方法 ,方法　用带 7号针头的注射器 ,于宫颈 3点、9点距宫颈外口约 1cm处水平穿刺进针约 3cm ,回抽无血后 ,分别推注 2 %盐酸利多卡因各 3ml,2min后手术。结果　子宫峡部阻滞麻醉后 ,疼痛明显减轻或消失 ,与对照组相比有极显著性差异 (P <0 .0 1) ,人工流产综合征发生率明显低于对照组 (P <0 .0 1)。结论　子宫峡部阻滞麻醉开展无痛人流安全、简便、有效。     

布比卡因和利多卡因硬膜外麻醉对心率变异性的影响

目的 探讨硬膜外腔使用不同局麻药对心脏自主神经系统的影响。方法 ３０例ＡＳＡⅠ～Ⅱ级的低位硬膜外麻醉病人,随机分布比卡因组（Ｂ组,ｎ＝１５）和利多卡因组（Ｌ组,ｎ＝１５）,两组均于麻醉前、硬膜外用药后５分钟、１０分钟、１５分钟及２０分钟获取ＨＲ、ＳＢＰ、ＤＢＰ、ＭＡＰ及心率变异超低频、低频、高频、超高频、总功率和低频高频比值。结果 Ｂ组心率变异性变化不显著。Ｌ组心率变异性各参数均有不同下降,但低频     

Etodolac in the management of pain: A clinical review of a multipurpose analgesic

Etodolac is a non-steroidal anti-inflammatory drug with analgesic properties. Its primary anti-inflammatory mechanism of action is through a selective effect on cyclo-oxygenase-2 (COX-2). It is rapidly absorbed after oral administration, and maximum plasma concentration (C_max) is reached in 1-2 h, with an elimination half-life (t1/2 ) of 6-8 h. Etodolac has been widely applied in the treatment of inflammatory arthritides such as rheumatoid arthritis, ankylosing spondylitis and gout and in osteoarthritis and has been shown to be efficacious and well tolerated. However, etodolac has other applications which rely primarily on its efficacy as an analgesic. In particular, etodolac has been evaluated in the treatment of a variety of different pain states. Etodolac has been observed to be efficacious in the treatment of acute pain following dental extraction, orthopaedic and urological surgery, and episiotomy, as well as in the treatment of pain due to acute sports injuries, primary dysmenorrhoea, tendonitis, bursitis, periarthritis, radiculalgia and low back pain. These studies indicate that etodolac is a multipurpose analgesic with many clinical applications in addition to its use in the treatment of inflammatory and degenerative forms of arthritis.     

Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines

Two ongoing selective breeding projects have produced mice that display divergent analgesic responses to morphine. These two projects have selected for similar phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland). Evidence suggests genetic commonalities between mice of the two projects. Using a Mendelian breeding protocol, we have recently found that one or two genetic loci predominantly determine the high morphine analgesia exhibited by HA mice. In the present study we demonstrate that the differential morphine analgesia (5 mg/kg. i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly determined by two unlinked loci. A complementation analysis, in which the analgesic responses to morphine of the recessive homozygotes of each project (HAR and HA) were compared to those of their hybrid offspring (HAR x HA), revealed that different genetic loci have been fixed in each project. An intriguing bimodal distribution was observed in the HAR x HA population: Some HAR x HA hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice were comparable to those of their low-line parents. These findings indicate not only that different loci were responsible for producing high morphine responders in each selection project but that these distinct loci can interact synergistically to produce superhigh and superlow responders.