士的宁敏感的甘氨酸受体对吸入麻醉药催眠和镇痛作用的影响

目的探讨士的宁(strychnine,Stry)敏感的甘氨酸受体(strychnine-sensitive glycine receptor,GlyR)与吸入麻醉药异氟烷、恩氟烷、七氟烷和乙醚催眠、镇痛作用的关系。方法建立小鼠腹腔注射吸入麻醉药催眠、镇痛模型,在催醒和热板实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量士的宁对小鼠睡眠时间(sleeping time,ST)和热板疼痛指数(pain index in hot-platetest,HPPI)的影响。结果催醒实验中,士的宁1、2、4μg icv对上述4种吸入麻醉药的ST均无影响(P>0.05);热板实验中,士的宁0.1、0.2、0.4μg it能够剂量依赖性地减少吸入麻醉药恩氟烷、七氟烷和乙醚镇痛小鼠的HPPI(P<0.05,P<0.01);士的宁0.1μg it对异氟烷镇痛小鼠的HPPI没有影响(P>0.05),0.2、0.4μg it可减少异氟烷镇痛小鼠的HPPI(P<0.05,P<0.01)。结论士的宁敏感的甘氨酸受体是吸入麻醉药异氟烷、恩氟烷、七氟烷和乙醚镇痛作用的重要靶位,但与其催眠作用关系不大。     

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。     

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。     

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。     

瞬时感受器电位香草酸受体1对异氟烷镇痛和催眠作用的影响

目的探讨瞬时感受器电位香草酸受体1(TRPV1)对异氟烷镇痛及催眠作用的影响。方法在热板法和扭体法镇痛实验中,80只小鼠随机均分为生理盐水(NS组)和异氟烷(异氟烷组,腹腔注射异氟烷1.0 ml/kg)两组;随后各组再均分为4个亚组,分别注射溶媒、辣椒素(125、250、500ng/kg)。记录热板法热板痛阈(HPPT)和扭体法扭体次数。催眠实验中,异氟烷组小鼠腹腔注射异氟烷1.0 ml/kg后,侧脑室注射溶媒、辣椒素(125、250、500 ng/kg),记录给药后小鼠的睡眠时间(ST)。结果与异氟烷+溶媒亚组相比,其余3个异氟烷+辣椒素亚组HPPT降低(P<0.05)、扭体次数增加(P<0.01),但ST无明显变化(P>0.05)。结论 TRPV1可能是异氟烷抗热刺激痛和内脏化学刺激痛的靶位之一,但与异氟烷的催眠作用关系不大。     

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。     

腹腔注射七氟烷对小鼠镇痛及催眠作用的影响

目的观察腹腔注射七氟烷（Sevolelurance,Sev）对小鼠镇痛及催眠作用的影响。方法小鼠腹腔注射七氟烷后用热板和扭体实验、催眠实验分别观察小鼠热板痛阈值（HPPT）、扭体次数（WT）和睡眠时间（ST）的变化。结果腹腔注射七氟烷能增大HPPT（P〈0．05,P〈0．01）,减少WT（P〈0．01）,延长ST（P〈0．01）。结论在本实验条件下,小鼠腹腔注射七氟烷可产生催眠和镇痛作用。     

恩氟烷镇痛作用与脊髓5-HT1A受体的关系

目的探讨恩氟烷镇痛作用与脊髓5-羟色胺受体1A(5-HT1AR)之间的关系。方法腹腔注射恩氟烷建立镇痛模型,用甩尾法、热板法和扭体法分别观察鞘内注射5-HT1AR特异性拮抗剂p-MPPF对小鼠甩尾潜伏期(TFL)、热板法痛阈(HPPT)和扭体次数(WTs)的影响。结果腹腔注射恩氟烷可产生镇痛作用(P<0.05);单用p-MPPF 4μg/只或8μg/只对小鼠TFL、HPPT和WTs均无明显影响(P>0.05);两个剂量的p-MPPF均能使恩氟烷镇痛小鼠的TFL、HPPT缩短和WTs增加(P<0.05)。结论恩氟烷镇痛作用与脊髓5-HT1AR密切相关。     

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     

昂丹司琼对异氟烷催眠和镇痛作用的影响

目的观察昂丹司琼对异氟烷催眠和镇痛作用的影响;探讨异氟烷的催眠、镇痛作用与5-羟色胺3受体(5-HT3)的关系。方法①催醒实验小鼠ip给予昂丹司琼1,2,4 mg·kg-1,15 min后ip给予异氟烷1.0 ml.kg-1催眠,检测翻正反射消失时间。②催眠半数有效量ED50测定小鼠ip给予昂丹司琼2 mg·kg-1,15 min后用序贯法ip给予异氟烷1.12,0.90,0.72,0.58和0.46 ml.kg-1,测定催眠ED50。③扭体法小鼠ip给予昂丹司琼1,2和4 mg·kg-1,10 min后sc给予异氟烷1.0 ml.kg-1镇痛,检测扭体次数。④热板法小鼠ip给予昂丹司琼1,2和4 mg·kg-1,10 min后,ip给予异氟烷0.4 ml.kg-1镇痛,检测小鼠热板法痛阈值(HPPT)。结果与正常对照组相比,昂丹司琼1,2和4 mg·kg-1组小鼠翻正反射消失持续的时间和ED50值均无明显变化。扭体实验中,与正常对照组比较,昂丹司琼4 mg·kg-1和异氟烷1.0 ml.kg-1可使清醒小鼠扭体次数减少(P<0.01),麻醉小鼠给予昂丹司琼1,2和4 mg·kg-1时,扭体次数有下降趋势,但无统计学差异。热板法中,ip昂丹司琼对清醒小鼠及异氟烷小鼠的HPPT均无明显影响。结论昂丹司琼对异氟烷催眠、抗热刺激伤害作用无明显影响,提示异氟烷的催眠镇痛作用可能与5-HT3受体无明显关系。     

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.     

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.     

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.     

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.     

Spinal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors may mediate the analgesic effects of emulsified halogenated anaesthetics

1. The present study was designed to investigate the relationship between spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the analgesic effects of emulsified halogenated anaesthetics. 2. After having established the mouse model of analgesia by intraperitoneal or subcutaneous injections of appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we injected different doses of AMPA intrathecally and observed effects on the pain threshold using the hot-plate and acetic acid-induced writhing tests. 3. The results showed that intrathecal injection of AMPA (0.25, 0.5 and 1.0 ng) did not affect the pain threshold on the hot-plate test or the writhing times in conscious mice. In contrast, AMPA (0.25, 0.5 and 1.0 ng intrathecally) significantly and dose-dependently decreased the pain threshold on the hot-plate test and increased the writhing times in mice treated with emulsified anaesthetics. 4. These results suggest that spinal AMPA receptors may be important targets for the analgesic effects of emulsified enflurane, isoflurane and sevoflurane.