1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase

A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.     

Differential Effects of Long-Term Electroconvulsive Shock on Brain Levels of Enkephalin and Humoral-Endorphin

Abstract: Electroconvulsive shock (ECS) administrations repeated for 10 consecutive days cause an elevation in the opioid content of the rat brain. Two different endogenous opioids, enkephalin and humoral-endorphin, undergo independent changes that differ in both their time course and intracerebral localization. These metabolic changes parallel long-term behavioral modifications such as the development and dissipation of tolerance to the analgesic effect of ECS. The activation of two different, independent, endogenous opioid systems by ECS is in agreement with previous behavioral and pharmacological studies.     

Analgesic effects of dynorphin-A and morphine in mice

To investigate whether or not dynorphin-A is analgesic, the effect of this peptide was tested in comparison with that of morphine in mice. Dynorphin-A produced a potent analgesic effect in the acetic acid writhing and tail pinch tests, but a weak effect in the tail flick test when given by intracerebroventricular injection. In contrast, morphine caused a potent analgesia in all the tests. Dynorphin-A was more effective when given by intrathecal injection than by intracerebroventricular injection, whereas morphine was equipotent by both injection routes. The results suggest that dynorphin-A is analgesic and that its analgesia may be differentiated from that of morphine.     

羟考酮在腹腔镜胆囊切除术后镇痛中的应用及对凝血功能的影响

目的:分析羟考酮在腹腔镜胆囊切除术后镇痛中的应用及对凝血功能的影响。方法:选择2015年5月~2016年5月于我院行腹腔镜胆囊切除术患者106例,依据抽签法分成对照组与实验组,各有53例,对照组予以芬太尼镇痛,实验组予以羟考酮镇痛,比较两组痛觉指标[5-羟色胺(5-HT)、P物质]、疼痛数字评分(NRS)、凝血功能[凝血酶原时间(PT)、纤维蛋白原(Fg)、活化部分凝血酶原时间(APTT)、血小板计数(PLT)]、血流动力学、炎症因子、应激指标、麻醉效果和安全性。结果:干预后,实验组5-HT、P物质水平、NRS评分、PT、Fg、APTT、PLT以及血流动力学、炎症因子、应激指标均低于对照组,差异具有统计学意义(P0.05)。两组麻醉效果比较差异无统计学意义(P0.05)。实验组不良反应率显著低于对照组(P0.05)。结论:腹腔镜胆囊切除术应用羟考酮的镇痛作用与芬太尼相当,但能够更有效减轻术后血液的高凝状态。     

连续股神经阻滞联合帕瑞昔布对全膝置换患者术后镇痛效果观察

目的:探讨连续股神经阻滞(CFNB)联合帕瑞昔布对全膝关节置换术(TKA)患者术后镇痛效果。方法:选择2015年1月至2016年12月间我院行择期单侧TKA治疗的患者100例,按照随机数字表法分为对照组和研究组,每组各50例。两组患者术后分别接受CFNB和CFNB联合帕瑞昔布镇痛,镇痛时间2 d。观察两组患者术后6 h、12 h、24 h、48 h静息状态和运动状态视觉模拟疼痛评分(VAS)以及术后不良反应发生率。并于术前1 d、术后1 d、2 d、3 d应用美国特种外科医院膝关节评分表(HSS)评定两组患者膝关节功能。结果:术后6 h、12 h、24 h、48 h研究组患者静息状态VAS评分和运动状态VAS评分显著低于对照组患者(P0.05)。两组恶心/呕吐、呼吸抑制、导管相关问题、尿潴留发生率比较无统计学差异(P0.05)。两组患者术前1d HSS评分比较无统计学差异(P0.05),术后1 d、术后2 d、术后3 d两组患者HSS评分均较术前1 d显著升高,且研究组患者HSS评分显著高于对照组(P0.05)。结论:CFNB联合帕瑞昔布具有镇痛效果好、安全可靠的优点,应用TKA术后镇痛有利于患者早期进行膝关节功能锻炼,值得临床推广。     

Discovery of aminocyclohexene analogues as selective and orally bioavailable hNav1.7 inhibitors for analgesia

hNav1.7 receives a lot of attention owing to its attractive mechanism of action in pain processing pathway. We have previously reported our design of a novel series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors. Herein, we disclose further efforts to the optimization of hit compound (?)-6, which led to the identification of aminocyclohexene analogues (?)-9 and (?)-17 with good potency, high selectivity, and minimal CYP inhibition. Both compounds (?)-9 and (?)-17 demonstrated improved pharmacokinetic profiles in rats, and robust efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL) models.     

辣椒素的镇痛作用

辣椒素是从辣椒中提取出来的一种具有镇痛作用的物质。通过激活感觉神经纤维上的瞬时感受器电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1),释放并消耗大量神经肽物质,使神经细胞对伤害性刺激产生脱敏化反应,进而发挥持久的镇痛作用而不影响运动功能。因而在难治性疼痛类疾病中,辣椒素具有独特的治疗价值。以辣椒素为主要成分的制剂已经在临床治疗中开展应用。特定位点注射辣椒素或其类似物resiniferatoxin可以减轻癌痛患者的疼痛症状。但由于辣椒素的治疗剂量与毒性剂量存在部分重叠,使得其在临床应用中受到一定程度的限制。不同的给药方式和作用部位所产生的作用效果可能不同。为深入了解辣椒素的镇痛作用及作用机制,充分发挥其治疗价值,现从不同给药途径总结近几年来辣椒素镇痛作用的研究成果。     

小茴香挥发油的抗炎镇痛作用

目的:研究小茴香挥发油的抗炎、镇痛作用,为指导临床合理用药提供科学依据。方法:应用二甲苯致小鼠耳廓肿胀、蛋清致大鼠足肿胀2种动物模型进行抗炎药效学实验;采用醋酸致小鼠扭体反应进行镇痛实验。结果:小茴香挥发油能显著抑制上述各种动物模型的炎症反应及醋酸引起的小鼠扭体反应。结论:小茴香挥发油具有抗炎和镇痛作用。     

小茴香挥发油的抗炎镇痛作用

目的：研究小茴香挥发油的抗炎、镇痛作用,为指导临床合理用药提供科学依据。方法：应用二甲苯致小鼠耳廓肿胀、蛋清致大鼠足肿胀2种动物模型进行抗炎药效学实验;采用醋酸致小鼠扭体反应进行镇痛实验。结果：小茴香挥发油能显著抑制上述各种动物模型的炎症反应及醋酸引起的小鼠扭体反应。结论：小茴香挥发油具有抗炎和镇痛作用。     

地塞米松对腰硬联合麻醉剖宫产术后腰背痛及神经并发症影响

目的：硬膜外腔注射地塞米松对腰硬联合麻醉腰背痛及神经并发症的预防效果。方法：将200例ASA I-II腰联合麻醉下择期剖宫产患者随机分成2组,A组吗啡2 mg＋生理盐水稀释至10ml硬膜外腔注射;B组向硬膜外腔注射吗啡2mg＋地塞米松5mg＋生理盐水稀释至10 ml硬膜外腔注射。术毕两组均行静脉术后镇痛。观察并记录患者术后24,72 h的腰背痛及神经并发症情况,同时记录每例患者试穿次数。结果：B组患者术后24,72 h的背痛发生率为11.0%,4.0%,明显低于A组（P〈0.05）;穿刺1次和2次及以上背痛的发生率分别为5.1%和19.5%,明显低于A组（P〈0.05）。两组72h内神经并发症差异无统计学意义。结论：硬膜外腔注射地塞米松有效预防腰硬联合麻醉剖宫产术后腰背痛,但对神经并发症的影响还有待进一步观察。