γ-羟基丁酸受体与恩氟烷、异氟烷镇痛、催眠作用的关系

目的探讨γ-羟基丁酸(gamma-hydroxybutyric acid,GHBA)受体与吸入麻醉药异氟烷和恩氟烷催眠、镇痛作用的关系。方法建立小鼠腹腔和皮下注射吸入麻醉药催眠、镇痛模型。在催醒、热板和扭体实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量GHBA受体拮抗剂NCS-382对小鼠睡眠时间(sleepingtime,ST)、热板疼痛指数(pain index in hot-plate test,HPPI)和扭体次数(writhing times)的影响。结果催醒实验中,NCS-3821、5、25μg icv均可使异氟烷和恩氟烷催眠小鼠的ST缩短(P<0.01);热板实验中,NCS-3821、5、25μg it对清醒和镇痛小鼠的HPPI没有影响(P>0.05);扭体实验中,皮下注射异氟烷和恩氟烷后引起小鼠的扭体次数减少(P<0.01),但NCS-3821、5、25μg it对清醒小鼠及镇痛小鼠的扭体次数均无明显影响(P>0.05)。结论γ-羟基丁酸受体是吸入麻醉药异氟烷和恩氟烷催眠作用的靶位之一,但与其抗热刺激伤害和抗化学内脏痛作用关系不大。     

AMPA对吸入麻醉药催眠、镇痛作用的影响

目的探讨AMPA(α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid,AMPA)对吸入麻醉药恩氟烷、异氟烷、七氟烷催眠、镇痛作用的影响。方法建立小鼠腹腔注射吸入麻醉药催眠、镇痛模型,在催眠和热板法实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量的AMPA对小鼠睡眠时间(sleep time,ST)和热板法痛阈值(pain threshold in hot-plate test,HPPT)的影响。结果催眠实验中,AMPA50、75、100ng组的ST与aCSF组相比,差异无统计学意义(P>0.05)。镇痛实验中,aCSF及AMPA0.25、0.5、1.0ng it对正常对照组小鼠的HPPT均无影响(P>0.05)。AMPA0.25、0.5、1.0ng it剂量依赖性地降低吸入麻醉药镇痛小鼠的HPPT(P<0.05或P<0.01)。结论脑内的AMPA受体与吸入麻醉药恩氟烷、异氟烷、七氟烷催眠作用的关系不大,脊髓的AMPA受体参与了吸入麻醉药恩氟烷、异氟烷、七氟烷的镇痛作用。     

神经元烟碱受体与异氟烷、七氟烷催眠和镇痛作用的关系

目的探讨神经元烟碱受体(neuronal nicotinic acetyl-choline receptors,nnAChRs)与异氟烷、七氟烷催眠和镇痛作用的关系。方法建立小鼠催眠、镇痛模型后,在催醒、热板和扭体实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量烟碱(nicotine,N)对小鼠睡眠时间(sleeping time,ST)、热板法痛阈(pain threshold in hot-plate test,HPPT)和扭体次数的影响。结果催醒实验中,烟碱10、20、40μgicv能够剂量依赖性地缩短异氟烷、七氟烷催眠小鼠的ST(P<0·05,P<0·01);热板实验中,烟碱5、10、15μgit对清醒小鼠HPPT没有影响(P>0·05),但能够剂量依赖性地减少异氟烷、七氟烷镇痛小鼠的HPPT(P<0·05,P<0·01);扭体实验中,皮下注射镇痛剂量的异氟烷、七氟烷后均能引起小鼠的扭体次数减少(P<0·01),但烟碱5、10、15μgit对异氟烷、七氟烷镇痛小鼠的扭体次数的影响差异均无显著性(P>0·05)。结论nnAChRs是异氟烷、七氟烷催眠作用的重要靶位;也是异氟烷、七氟烷抗热刺激伤害的重要靶位,但与其抗化学内脏痛作用关系不大。     

吸入麻醉药镇痛、催眠作用与GABA_A受体的关系

目的　分析吸入麻醉药安氟醚、异氟醚和七氟醚催眠、镇痛作用与GABAA 受体的关系。方法　建立小鼠催眠、镇痛模型后 ,在小鼠催醒、热板、扭体实验中 ,分别观察用药后小鼠翻正反射消失持续时间、痛阈或扭体次数的变化。结果　一叶秋碱和荷包牡丹碱对上述 3种吸入麻醉药的催眠、镇痛作用的影响均无显著性 (P >0 0 5 )。结论　GABAA 受体并非安氟醚、异氟醚和七氟醚催眠、镇痛作用的主要靶位     

侧脑室或鞘内注射烟碱对恩氟烷催眠和镇痛作用的影响

目的初步分析恩氟烷的催眠和镇痛作用与神经元烟碱受体之间的关系。方法催醒实验:小鼠ip恩氟烷2.2mL.kg-1,翻正反射消失1min后,分别脑室注射烟碱10,20和40μg(5μL),记录翻正反射恢复时间(即睡眠时间)。镇痛实验:①甲醛实验:小鼠ip恩氟烷0.5mL.kg-1,5min后分别鞘内注射烟碱5,10和15μg(5μL),再5min后于足底皮下注射2%甲醛溶液20μL,记录60min内小鼠舔被注射足的累积时间。②热板实验:给药方法同甲醛实验,于注射烟碱后5,10,15,20和25min记录小鼠足部接触热板至开始添后足的时间作为后足痛阈。结果脑室注射烟碱能明显减少恩氟烷催眠小鼠的睡眠时间;鞘内注射烟碱不能拮抗甲醛实验中恩氟烷的镇痛作用,但可拮抗热板实验中恩氟烷的镇痛作用。结论神经元烟碱受体可能是恩氟烷催眠作用的重要靶位之一;也可能是恩氟烷对热刺激镇痛作用的重要靶位之一,而非对化学、炎性刺激镇痛作用的靶位。     

异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系

目的分析异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系。方法建立小鼠异氟烷注射催眠、镇痛模型后,在小鼠催醒、甩尾、福尔马林实验中,观察侧脑室或鞘内注射NMDA受体甘氨酸位点的激动剂D-丝氨酸(D-Serine,D-Ser)后小鼠睡眠时间、甩尾潜伏期或累计舔足时间的变化;用免疫组化方法观察异氟烷及鞘内用药对福尔马林小鼠脊髓Fos蛋白表达的影响。结果侧脑室注射D-Ser对异氟烷的催眠时间无影响(P>0.05)。鞘内注射D-Ser(0.025、0.05、0.1ng)可拮抗甩尾实验、福尔马林实验Ⅰ相中异氟烷的镇痛作用(P<0.05,P<0.01),而对福尔马林实验Ⅱ相异氟烷的镇痛作用无影响(P>0.05)。鞘内注射D-Ser0.05ng可拮抗异氟烷对福尔马林小鼠脊髓Fos蛋白表达的抑制作用(P<0.01)。结论异氟烷催眠作用与脑内NMDA受体甘氨酸位点关系不大;脊髓NMDA受体甘氨酸位点介导异氟烷对热、化学刺激的镇痛作用,而与异氟烷对慢性炎性疼痛的镇痛作用无明显关系。     

鞘内注射NMDA拮抗吸入麻醉药的镇痛作用

目的探讨脊髓NMDA受体与吸入麻醉药安氟醚、异氟醚、七氟醚镇痛作用的关系。方法建立小鼠注射吸入麻醉药镇痛模型,用热板法和扭体法实验分别观察鞘内注射(it)不同剂量的NMDA对其痛阈的影响。结果NMDA2.5、5、10 ng it对清醒小鼠热板法痛阈(Pain threshold in hot-p late test,HPPT)和扭体次数无明显影响(P>0.05);NMDA2.5、5、10 ng it可剂量依赖性地减少安氟醚、异氟醚、七氟醚镇痛小鼠的HPPT(P<0.05)和增加扭体反应的次数(P<0.05)。结论脊髓的NMDA受体是吸入麻醉药安氟醚、异氟醚、七氟醚镇痛作用的重要靶位。     

侧脑室注射士的宁对七氟烷致小鼠遗忘作用的影响

目的观察士的宁敏感的甘氨酸受体与七氟烷遗忘作用的关系。方法建立小鼠腹腔注射七氟烷遗忘模型,用跳台、避暗实验,观察不同剂量士的宁(0.05,0.10,0.15μg)侧脑室注射对小鼠跳台实验跳下潜伏期(SDL)、避暗实验步入潜伏期(STL)以及跳台和避暗实验错误(电击)次数的影响。结果与生理盐水组相比,士的宁对小鼠的SDL、STL和错误次数均无明显影响;七氟烷可明显减少小鼠的SDL和STL,增加错误次数(P<0.05)。士的宁可明显延长七氟烷所致记忆障碍小鼠的SDL、STL,减少错误次数(P<0.05)。结论士的宁敏感的甘氨酸受体介导了七氟烷的遗忘作用。     

侧脑室注射烟碱拮抗恩氟烷的催眠、遗忘作用

目的探讨神经元烟碱受体(neuronal nicotinic acetyl-choline receptor,nnAchR)与吸入麻醉药恩氟烷催眠、遗忘作用的关系。方法小鼠腹腔注射不同剂量的恩氟烷(2.2,0.4ml.kg-1)建立模型,催醒实验中观察不同剂量的烟碱(nicotine,N)侧脑室注射(intracerebroventricular,icv)对小鼠睡眠时间(sleeping time,ST)的影响;跳台、避暗实验中观察不同剂量的烟碱icv对跳台潜伏期(step down latency,SDL)、步入潜伏期(step through latency,STL)和错误次数的影响。自主活动实验观察恩氟烷(0.4ml.kg-1)对小鼠自主活动次数的影响。结果和对照组相比,脑室注射烟碱能缩短恩氟烷麻醉小鼠的ST,延长恩氟烷所致记忆障碍小鼠的SDL、STL,减少错误次数。0.4ml.kg-1腹腔注射对小鼠自主活动无明显影响。结论本实验结果提示脑内的神经元烟碱受体是恩氟烷催眠、遗忘作用的重要靶位之一。     

异丙嗪对异氟烷小鼠镇痛、催眠、遗忘作用和治疗指数的影响

目的观察异丙嗪对异氟烷镇痛、催眠、遗忘作用和治疗指数的影响。方法用热板法和扭体法观察异丙嗪对异氟烷镇痛作用的影响,翻正反射法观察异丙嗪对异氟烷小鼠睡眠时间的影响,Morris水迷宫法观察异丙嗪对异氟烷小鼠遗忘作用的影响,并用序贯法观察异丙嗪对异氟烷小鼠催眠ED50、LD50的影响。结果在热板法和扭体法实验中,异丙嗪增强了异氟烷的镇痛作用(P<0.05或P<0.01);在翻正反射实验中,异丙嗪可延长异氟烷小鼠的睡眠时间(P<0.01);在水迷宫实验中,异丙嗪组和异氟烷组的平均逃避潜伏期均少于两药合用组(P<0.05或P<0.01),第3象限停留时间均多于两药合用组(P<0.01或P<0.05),异氟烷组原平台穿越次数多于合用组(P<0.05);异丙嗪可降低异氟烷小鼠的催眠ED50(P<0.01),而对其LD50无影响(P>0.05)。结论异丙嗪可以增强异氟烷的镇痛、催眠和遗忘作用,并可以提高异氟烷的治疗指数。     

Strychnine-sensitive glycine receptors mediate the analgesic but not hypnotic effects of emulsified volatile anesthetics

The present study was designed to investigate the role of strychnine-sensitive glycine receptors in hypnosis and analgesia induced by emulsified volatile anesthetics. After having established the mice model of hypnosis and analgesia by intraperitoneally injecting (i.p.) appropriate doses of ether, enflurane, isoflurane or sevoflurane, we intracerebroventricularly (i.c.v.) or intrathecally (i.t.) injected different doses of strychnine and then observed the effects on the sleeping time using the awaken test and the pain index in hot-plate test (HPPI) using the hot-plate test. In the awaken test, strychnine 1, 2, 4 microg (i.c.v.) had no distinctive effect on the sleeping time of the mice treated with the four emulsified inhalation anesthetics mentioned above (p > 0.05); in the hot-plate test, strychnine 0.1, 0.2, 0.4 microg (i.t.) can significantly and dose-dependently decrease the HPPI of the mice treated with emulsified ether, enflurane and sevoflurane (p < 0.05, p < 0.01); strychnine 0.1 microg (i.t.) did not affect the HPPI of the mice treated with emulsified isoflurane (p > 0.05), but 0.2 and 0.4 microg (i.t.) can significantly decrease the HPPI of the mice treatedwith emulsified isoflurane (p < 0.05, p < 0.01). These results suggest that strychnine-sensitive glycine receptors may contribute to the analgesic but not to the hypnotic effects induced by ether, enflurane, isoflurane and sevoflurane.     

Involvement of kainate receptors in the analgesic but not hypnotic effects induced by inhalation anesthetics

In the present study, the role of kainate (KA) receptors in hypnosis and analgesia induced by emulsified inhalation anesthetics was investigated. A mouse model of hypnosis and analgesia was established by an intraperitoneal injection of emulsified enflurane, isoflurane or sevoflurane. We intracerebroventricularly (icv) or intrathecally (it) administered KA, a KA receptor agonist to mice. The effects of the KA on the sleep time were observed using a hypnosis test, and the tail-withdrawal latency was analyzed using the tail-withdrawal test. In the hypnosis test, KA (2.5, 5 or 10 ng; icv administered) treatment had no distinctive effects on the sleep time of mice treated with emulsified inhalation anesthetics. In the tail-withdrawal test, KA (0.2, 0.4 or 0.8 ng; it administered) treatment significantly and dose-dependently decreased the tail-withdrawal latency of mice treated with emulsified anesthetics. These results suggested that KA receptors may modulate the analgesic but not hypnotic effects induced by emulsified enflurane, isoflurane or sevoflurane.     

Spinal N-methyl-D-aspartate receptors may mediate the analgesic effects of emulsified halogenated anesthetics

The present study was designed to investigate the relationship between spinal cord N-methyl-D-aspartate (NMDA) receptors and the analgesic effects of emulsified halogenated anesthetics. After having established the mouse model of analgesia by intraperitoneally or subcutaneously injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intrathecally injected different doses of NMDA and then observed the effects on the pain threshold using the hot-plate test and the acetic acid-induced writhing test. The results showed that intrathecal injection of NMDA (2.5, 5 and 10 ng) did not affect the pain threshold on the hot-plate test or the writhing times in conscious mice (p > 0.05); in contrast, NMDA (2.5, 5 and 10 ng intrathecally) can significantly and dose dependently decrease the pain threshold on the hot-plate test (p < 0.05 or p < 0.01) and increase the writhing times (p < 0.05 or p < 0.01) in the mice treated with emulsified anesthetics. These results suggest that spinal NMDA receptors may be important targets for the analgesic effects of emulsified enflurane, isoflurane and sevoflurane.     

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors participate in the analgesic but not hypnotic effects of emulsified halogenated anaesthetics

The present study was designed to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hypnosis and analgesia induced by emulsified inhalation anaesthetics. After having established the mice model of hypnosis and analgesia by intraperitoneally injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intracerebroventricularly or intrathecally injected different doses of AMPA and then observed the effects on the sleep time using hypnosis test and the tail-withdrawal latency using the tail-withdrawal test. In hypnosis test, AMPA (50, 75 and 100 ng, intracerebroventricularly) had no distinctive effects on the sleep time of the mice treated with emulsified inhalation anaesthetics (P > 0.05). In tail-withdrawal test, AMPA (0.25, 0.5 and 1.0 ng, intrathecally) significantly and dose-dependently decreased the tail-withdrawal latency (P < 0.05 or P < 0.01) in the mice treated with emulsified anaesthetics. These results suggest that AMPA receptors may participate in the analgesic but not in the hypnotic effects induced by emulsified enflurane, isoflurane or sevoflurane.     

侧脑室或鞘内注射NCS-382对七氟烷催眠及镇痛作用的影响

目的探讨γ-羟基丁酸(GHB)受体与七氟烷(sevoflurane)催眠及镇痛作用的关系。方法①催醒实验小鼠ip七氟烷5.5 ml.kg-1催眠后i,cv给予NCS-382 0.050,.25和1.25 mg.kg-1,检测翻正反射消失时间。②镇痛实验小鼠分为ip七氟烷2.0 ml.kg-1镇痛和生理盐水2大组,每组再分为ith人工脑脊液(aCSF),NCS-382 0.050,.25和1.25 mg.kg-1亚组,热板检测热板疼痛指数(HPPT)。③扭体实验小鼠分为sc七氟烷5.5 ml.kg-1镇痛和生理盐水2大组,再分为ith给予aCSF,NCS-382 0.050,.25和1.25 mg.kg-1亚组,检测扭体次数。结果与七氟烷模型组相比,小鼠七氟烷催眠后i,cv给予NCS-382 0.05,0.25和1.25mg.kg-1,可明显缩短翻正反射消失时间,分别提前50,52和78 min(P<0.01)。热板法中i,th给予NCS-382对清醒小鼠HPPT无明显影响,但能使麻醉小鼠的HPPT分别降低4.4,5.7和4.4 s(P<0.01)。扭体实验中,与正常对照组相比s,c给予七氟烷可使小鼠的扭体次数减少14次(P<0.01),但ith给予NCS-382对清醒及麻醉小鼠扭体次数无明显影响。结论 GHB可能是七氟烷催眠作用和抗热刺激伤害的靶位之一,但与其抗化学刺激和炎症刺激作用可能无关。