Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

硬膜外高渗氯化钠溶液术后镇痛的临床双盲研究

为观察高渗盐水硬膜外注射术后镇痛效果,用双盲法对60例病人进行了研究。生理盐水对照级术后镇痛优良率为3.33％,镇痛有效率为10％,均需用镇痛药;高渗盐水组术后镇痛优良率为86.67％,有效率为96.67％,很少使用镇痛药。两组差别显著(P<0.05,P<0.01)。对其他感觉和运动功能无明显影响。高渗盐水组与吗啡组比较镇痛效果相同(P>0.05),副作用少(P<0.01)。说明硬膜外高渗氯化钠溶液是一种安全有效的镇痛方法,有较高推广应用价值。     

小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

Post-surgical pain relief with zero-order intravenous infusions of meptazinol and morphine: a double-blind placebo-controlled evaluation of their effects on ventilation

Summary A double-blind, placebo-controlled study has been made of the analgesic and respiratory effects of constant rate infusions of meptazinol and morphine in 30 patients after abdominal surgery. Group I received meptazinol, loading dose 50 mg followed by i.v. infusion 0.5 mg · kg⁻¹ · h⁻¹, Group II received morphine, loading dose 5 mg and then an infusion of 0.05 mg · kg⁻¹ · h⁻¹, and Group III received saline. After recovery from inhalation anaesthesia (without opiates or a local anaesthetic) pain relief and chemoreceptor carbon dioxide tolerance were assessed before and at various times after starting the analgesic infusion. A similar degree of pain relief was found after 10 min in Groups I and II, which lasted until the end of observation period (20 h). Heart rate and systolic and diastolic blood pressures were lower in Group II than in Groups I and III, and respiratory rate fell in Groups I and II. After 6 h arterial carbon dioxide tensions (P_aCO₂) became significantly higher in Group II than Group III. The maximum percentage fall in mean tidal volume (V_T) and expired minute volume (0V_E) from the preinjection values was significant in Groups I and II. End-tidal carbon-dioxide (P_ETCO₂) and P_aCO₂ were significantly higher after 20 h of infusion in Group II compared to Group I. The slope of 0V_E/P_ETCO₂ (<S>) was increased in Group I and it was significantly reduced in Group II. Analysis of derived variables, such as the CO₂ intercept (CO₂I) and minute ventilation at 7 kPa (0V_E7), indicated a shift to the right of the slopes in Groups I and II, initially more so in Group I. It is concluded that constant rate infusions of meptazinol and morphine were effective in providing postoperative pain relief. However, their effects on the central regulation of respiration were different, as meptazinol did not impair CO₂ sensitivity whereas morphine did.     

THE EFFECT OF SOME α2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

1. The effects of graded doses of the α₂-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the α₂-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.     

2-chloroprocaine antagonism of epidural morphine analgesia

Background: 2-chloroprocaine (2-CP) used for lumbar epidural anesthesia (LEA) reportedly decreases the efficacy of epidural morphine (EM) administered for post-cesarean section (CS) analgesia. The amount of supplemental i.v. morphine self-administered by the patient via the patient-controlled analgesia device (PCA) is used to study the interaction between EM and 2-CP.
Methods: Forty-two patients scheduled for elective CS were randomly divided into 3 equal groups, and received 2-CP, 2-CP+epinephrine (Epi, 5 μg ml^-1) or 2% lidocaine (Lido) with Epi for LEA. All patients received 5 mg EM and i.v. PCA morphine for postoperative pain. Cumulative amount of i.v. morphine used in the first 24 hours as well as the amount of the drug used during each 2-h period were noted. Nonparametric analysis of variance and Chi-squared analysis were used for statistical comparisons.
Results: The mean cumulative 24-h i.v. PCA morphine requirement in the 2-CP, 2-CP+Epi and Lido+Epi groups respectively was 20.5±24, 33.1.5±27 and 4.07±6.3 (mean±SD). The Lido+Epi group used significantly less morphine ( P = 0.01) compared to either of the 2-CP groups with no significant difference between the 2-CP groups. The maximum i.v. PCA morphine use occurred in the first 4 hours following surgery in all three groups.
Conclusion: Analgesic efficacy of EM is decreased when 2-CP is used for LEA compared to when Lido+Epi is used.     

吗啡抑制大鼠多觉型伤害性感受器持续放电

作利用复合致痛剂引起大鼠尾部皮肤多觉型伤害性感受器（ＰＭＮ）持续性放电模型，经股静脉注入吗啡（４ｍｇ／ｋｇ），显抑制ＰＭＮ持续性放电。吗啡抑制ＰＭＮ放电５０％的潜伏期为１０±４．５ｍｉｎ，抑制时程超过３０ｍｉｎ。纳络酮１ｍｇ／ｍｇ ｉｖ，可翻转吗啡的抑制作用。在慢性吗啡耐受大鼠，吗啡几乎失去其抑制作用。吗啡引起的ＰＭＮ放电数变化不呈一致关系。小剂量吗啡（１ｍｇ／ｋｇ）注入支配感受野皮肢的尾动脉     

The effect of subhypnotic doses of propofol on the incidence of pruritus after intrathecal morphine for Caesarean section

The effect of subhypnotic doses of propofol on intrathecal morphine-induced pruritus was studied in a prospective, randomly allocated, double-blind controlled trial. Fifty-eight women undergoing elective lower segment Caesarean section for a singleton fetus received spinal anaesthesia with 2.5 ml hyperbaric 0.5% bupivacaine and 0.2 mg of preservative-free morphine. They then received propofol 1 ml (10 mg) or Intralipid 1 ml (control group) intravenously after delivery. Pruritus was assessed using a five-point verbal rating scale at hourly intervals for 8 h. A second dose of their allocated treatment drug was administered at the first recording of significant pruritus. The pruritus score was reassessed after 5 min and the treatment was repeated if pruritus remained. There were no differences between the groups in the onset of pruritus or its successful treatment. No adverse side-effects were associated with this dose of propofol. There were no differences in the incidence of post-operative nausea and vomiting between the two groups. Subhypnotic propofol is not an effective treatment for intrathecal morphine-induced pruritus in women following Caesarean section.