吗啡依赖性大鼠模型的建立

目的 :建立吗啡依赖性大鼠实验动物模型。方法 :以剂量递增法形成吗啡依赖模型 ,用纳洛酮催促戒断 ,戒断症状按柳田知司评分法给予评分。结果 :吗啡组戒断症状分值为 19.6 3± 3.4 6 :生理盐水对照组的戒断分值为 6 .2± 1.6 ,两组相比有显著性差异 (p <0 .0 1)。结论 :成功建立了吗啡依赖性大鼠模型     

Quantifying the incidence of clinically significant respiratory depression in women with and without obesity class III receiving neuraxial morphine for post-cesarean analgesia: a retrospective cohort study

BackgroundObesity is a suspected risk factor for respiratory depression following neuraxial morphine for post-cesarean analgesia, however monitoring guidelines for obese obstetric patients are based on small, limited studies. We tested the hypothesis that clinically significant respiratory depression following neuraxial morphine occurs more commonly in women with body mass index (BMI) ≥40 kg/m² compared with BMI <40 kg/m².MethodsWe conducted a single-center, retrospective chart review (2006–2017) of obstetric patients with clinically significant respiratory depression following neuraxial morphine, defined as: (1) opioid antagonist administration; (2) rapid response team activation (initiated in April 2010); or (3) tracheal intubation due to a respiratory event. The incidence of respiratory depression was compared between women with BMI ≥40 kg/m² and BMI <40 kg/m².ResultsIn total, 11 327 women received neuraxial morphine (n=1945 BMI ≥40 kg/m²; n=9382 BMI <40 kg/m²). Women with BMI ≥40 kg/m² had higher rates of sleep apnea, hypertensive disorders, and magnesium administration. Sixteen cases of clinically significant respiratory depression occurred within seven days postpartum. The incidence did not significantly differ between groups (odds ratio 2.2, 95% CI 0.6 to 6.9, P=0.174). Neuraxial morphine was not deemed causative in any case, however women with BMI ≥40 kg/m² had higher rates of tracheal intubation unrelated to neuraxial morphine (2/1945 vs. 0/9382, P=0.029).ConclusionsRespiratory depression in this population is rare. A larger sample (∼75 000) is required to determine whether the incidence is higher with BMI ≥40 kg/m². Tracheal intubation was higher among the BMI ≥40 kg/m² cohort, likely due to more comorbidities.     

Different spinal effects of opioid agonists on spinal and spino-bulbo-spinal reflexes in rats

Summary The effects of morphine-HCl (MOR), methionine-enkephalin (ME) and dynorphin_1–13 (DYN) on spinal and spino-bulbo-spinal (SBS) reflexes were studied. Although spinal intrathecal administration of MOR (15g) did not produce any apparent effect on these reflexes, systemically administered MOR (3mg/kg i.v.) reduced the electrical toe stimulation-induced SBS reflex. Furthermore, MOR (3mg/kg i.v.) increased the polysynaptic reflex induced by electrical stimulation of low-threshold dorsal root afferents in intact (non-spinal) rats, but not in spinal rats. Intrathecally administred DYN (0.5 and 5 g) reduced both the electrical toe stimulation-induced spinal and SBS reflexes, while ME (15g) only reduced the SBS reflex. These results indicate the physiological multiplicity of spinal opioid receptors. MOR may affect supraspinal nuclei but not the spinal pathway which possesses MOR-sensitive opioid receptors, whereas ME and DYN affect spinal opioid peptide receptors and modulate the reflex activities in which they participate.     

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)     

复方延胡索颗粒的制备、质控与初步戒毒作用的研究

目的：研究复方延胡索颗粒的制备、质量控制方法、观察该制剂对吗啡依赖鼠的治疗作用。方法：选用黄芪、延胡索、甘草、远志、酸枣仁、石菖蒲、芸香等七种中药组方制备复方延胡索颗粒,以有效部位部性物碱及有效成分四氢帕马丁的含量作为制备方法的筛选指标及复方延胡索颗粒制的质控指标。总生物碱的含量用非水电位滴定法测定,四氢帕马丁的含量以单波长反射锯齿式薄层扫描外标两点法测定,以该中药制剂治疗吗啡依赖性大鼠自然戒断模型体质量变化百分率作为初步戒毒作用的观察指标。结果：四氢帕马丁在1－6μg范围内线性关系良好（r=0.9992)其仪器精密度、同板精密度良好（RSD＜3．0％）,且在显色后0．5－6h内结果稳定,制剂的加样回收率约为975,复方延胡索颗粒中剂量组（0．6g/kg)和高剂量组（1．2g/kg)对吗啡依赖鼠的体质量下降可产生显治疗作用（P＜0．05,P＜0．01）。结论：本制剂一定剂量可有效控制吗啡身体依赖性大鼠戒断后的体质量下降,对吸毒可能有促进康复的作用。     

Comparison of the Disposition of Hepatically-Generated Morphine-3-glucuronide and Morphine-6-glucuronide in Isolated Perfused Liver from the Guinea Pig

Purpose. Humans and guinea pigs metabolise morphine extensively, forming the isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in relatively similar ratios. Both metabolites are formed in the liver, and their greater polarity relative to the parent aglycone may limit their permeability across hepatic membranes. This study compared the disposition of hepatically-generated M3G and M6G in perfused livers isolated from guinea pigs. Methods. Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs bicarbonate buffer containing morphine (6 to 7 M). Perfusing medium, venous perfusate and bile were collected at regular intervals and concentrations of morphine, M3G and M6G determined by reversed-phase HPLC. Results. Concentrations of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G and M6G were consistent between 20 and 50 min of perfusion. The mean (±s.d.) ratio for the rate of formation of M3G relative to M6G was 3.7 ± 1.5. A mean 33 ± 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of the M3G and M6G formed during a single passage, 19 ± 11% and 9 ± 9%, respectively, was excreted into bile; the values were significantly different (P = 0.002). Conclusions. A greater fraction of hepatically-generated M3G excreted into bile compared to that for M6G reflects differences in their relative transport across sinusoidal and canalicular membranes of hepatocytes, possibly via carrier-mediated systems.     

食管癌术后一次性硬膜外注射和肌肉注射镇痛法的比较

目的：确定硬膜外一次性镇痛法对食管癌病人术后的镇痛效果和减少并发症的意义。方法：９３ 例病人随机分成实验组（ Ｔ 组,５１ 例） 和对照组（ Ｃ 组,４２ 例） , Ｔ 组于手术结束缝合皮肤切口时经硬膜外导管于 Ｔ６ － ７ 水平注射吗啡１ ｍｇ 加１ ％ 普鲁卡因１０ ｍｌ, Ｃ 组用阿片类药物肌肉注射镇痛。结果： Ｔ 组病人术后疼痛明显减轻,各种并发症显著下降。结论：硬膜外一次性镇痛效果确切,操作方便,副作用少,对降低术后心肺并发症很有意义,尤其对年龄大、心肺功能差的病人较适合。     

麻黄素并吗啡硬膜外注射的术后镇痛效果

①目的　探讨麻黄素并吗啡硬膜外注射的术后镇痛效果。②方法　对１２６ 例泌尿外科开放手术后的病人进行间断硬膜外腔注射吗啡（２ｍ ｇ）、麻黄素（２０ｍ ｇ）,观察其镇痛效果,并与４０ 例单用吗啡（ ２ｍ ｇ）者进行对照。③结果　吗啡、麻黄素的镇痛作用强而持久,一次用药有效时间为（２８．４±３．５）ｈ,较对照组的（１８．１±２．６）ｈ 明显延长（ｔ＝ １７．１,Ｐ＜ ０．０１）。未见出现血压波动者。④结论　吗啡加麻黄素硬膜外腔注射是安全、长效的术后镇痛方法,特别适用于术后留置导尿或尿流改道的泌尿外科开放手术。     

Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty

BACKGROUND: After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus "on-demand" intravenous analgesia to "on-demand" intravenous analgesia alone. METHODS: Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones. RESULTS: No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group. CONCLUSION: Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.     

Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal

The activity of mesolimbic dopaminergic neurons was investigated in rats at various times after a chronic regimen of morphine, which produced, upon suspension, a marked somatic withdrawal syndrome. Single-cell extracellular recording techniques, coupled with antidromic identification from the nucleus accumbens, were used to monitor neuronal activity while behavioural observations allowed quantification of the somatic signs of morphine withdrawal. Temporal correlation of electrophysiological indices, such as firing rate and burst firing, with scores obtained through behavioural assessments proved negative, in that somatic signs were pronounced at 24 h after suspension of treatment and then subsided to control values at 72 h after the last morphine injection. In contrast, the firing rate and burst firing of mesolimbic dopaminergic neurons were found to be reduced at 1, 3 and 7 days after morphine withdrawal. After 14 drug-free days, electrophysiological analysis revealed an apparent normalization of various parameters. However, at this time, intravenous administration of morphine produced an increment of electrical activity which was significantly higher than that obtained in control (saline treated) rats. Further, administration of the opiate antagonist naltrexone, administered without prior morphine, at 3, 7 and 14 days after the last morphine administration, failed to alter dopaminergic neuronal activity. The results indicate: (i) that the activity of mesolimbic dopaminergic neurons remains reduced well after somatic signs of withdrawal have disappeared; (ii) after 14 days of withdrawal, the augmented magnitude of the electrophysiological response to exogenous morphine suggests an increased sensitivity of opiate receptors; and (iii) the lack of relationship between dopaminergic activity and somatic signs of withdrawal corroborates the notion that dopaminergic activity in the mesolimbic system does not participate in the neurobiological mechanisms responsible for somatic withdrawal. The present results may be relevant to the phenomenon of drug addiction in humans and consequent relapse after drug-free periods.