通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎患者血清炎症因子和疼痛介质的影响

摘要 目的：观察通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎（KOA）患者血清炎症因子和疼痛介质的影响。方法：选择2021年6月-2022年12月期间石家庄市人民医院收治的早期KOA患者80例,采用随机数字表法将患者分为对照组（塞来昔布,40例）和观察组（通滞苏润江胶囊联合塞来昔布,40例）。对比两组疗效、疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分、炎症因子和疼痛介质。结果：观察组临床总有效率高于对照组（P<0.05）。两组治疗1个月后VAS、WOMAC评分下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后前列腺素E₂（PGE₂）、P物质（SP）下降,且观察组低于对照组同时间点（P<0.05）。两组不良反应发生率对比未见统计学差异（P>0.05）。结论：塞来昔布和通滞苏润江胶囊联合治疗早期KOA患者,可缓解疼痛,提高临床治疗效果,改善关节功能,同时还可改善血清炎症因子和疼痛介质水平。     

腕踝针联合耳穴压豆治疗肝癌癌痛的疗效及对心理状态和血清疼痛介质的影响

摘要 目的：观察腕踝针联合耳穴压豆治疗原发性肝癌（PHC）癌痛的疗效及对心理状态和血清疼痛介质的影响。方法：选取湖南中医药大学第一附属医院2020年3月~2022年12月期间收治的PHC癌痛患者117例,按随机数字表法分为对照组和联合组,例数分别为58例和59例。两组患者均接受常规疼痛处理,对照组患者接受耳穴压豆治疗,联合组在对照组的基础上接受腕踝针治疗。对比两组疼痛缓解率、临床指标、心理状态和疼痛介质水平。结果：联合组的疼痛缓解率高于对照组（P<0.05）。联合组的数字疼痛法（NRS）评分低于对照组,止痛起效时间、每次疼痛持续时间短于对照组,爆发痛次少于对照组（P<0.05）。治疗后,两组焦虑自评量表（SAS）、抑郁自评量表（SDS）评分下降,且联合组低于对照组（P<0.05）。治疗后,两组5-羟色胺（5-HT）、P物质（SP）、前列腺素E₂（PGE₂）下降,且联合组低于对照组（P<0.05）。结论：腕踝针联合耳穴压豆治疗PHC癌痛,可有效减轻疼痛症状,降低血清疼痛介质水平,同时还可有效调节患者的心理状态,应用价值较好。     

不同剂量艾司氯胺酮对腹腔镜全子宫切除术患者术后疼痛和情绪状态的影响

摘要 目的：探讨不同剂量艾司氯胺酮对腹腔镜全子宫切除术患者术后疼痛和情绪状态的影响。方法：按照随机数表法,选择2022年1月至2023年4月我院行腹腔镜全子宫切除术患者120例分为对照组（A组,n=40）、艾司氯胺酮0.25 mg/kg组（B组,n=40）、艾司氯胺酮0.5 mg/kg组（C组,n=40）。比较三组组围术期指标、术后1、4、8、24 h和48 h的疼痛评定数字量表（NRS）评分及术前1天（PRE1）、术后第1天（POD1）、术后第2天（POD2）的焦虑自评量表（SAS）评分、抑郁自评量表（SDS）评分、血流动力学指标及不良反应。结果：B组和C组术后24 h舒芬太尼镇痛药物用量、补救镇痛例数小于A组,A组、B组苏醒时间、拔管时间短于C组（P＜0.05）。B组、C组术后1 h的NRS评分低于A组（P＜0.05）,B组术后4 h、8 h、24 h的NRS评分低于A组,术后4 h、8 h的NRS评分低于C组（P＜0.05）。与组内PRE1相比,三组POD1的SAS、SDS评分均升高（P＜0.05）。B组、C组POD1、POD2的SAS、SDS评分均低于A组,且C组低于B组（P＜0.05）。与组内PRE1相比,A组POD2的SAS、SDS评分升高（P＜0.05）。与组内PRE1相比,B组POD2的SDS与C组POD2的SAS、SDS均降低（P＜0.05）。在T3时刻,B组和C组的平均动脉压（MAP）、心率（HR）低于A组（P＜0.05）。B组和C组术后恶心呕吐发生率低于A组（P＜0.05）;A组和B组术后头晕、苏醒延迟的发生率低于C组（P＜0.05）;三组术后苏醒期躁动和呼吸抑制的差异无统计学意义（P＞0.05）。结论：0.25 mg/kg的艾司氯胺酮对减轻腹腔镜全子宫切除术患者术后疼痛,减少阿片类药物用量,改善负面情绪的临床效果更佳。     

Design,synthesis and SAR of substituted indoles as selective TrkA inhibitors

A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported.     

The discovery of tetrahydropyridine analogs as hNav1.7 selective inhibitors for analgesia

hNav1.7 small molecular inhibitors have attracted lots of attention by its unique analgesic effect. Herein, we report the design and synthesis of a novel series of tetrahydropyridine analogs as hNav1.7 inhibitors for analgesia. Detail structural–activity relationship (SAR) studies were undertaken towards improving hNav1.7 activity, in vitro ADME, and in vivo PK profiles. These efforts resulted in the identification of compound (?)-15h, a highly potent and selective hNav1.7 inhibitor with good ADME and PK profiles.     

Discovery of AAT-008, a novel,potent, and selective prostaglandin EP4 receptor antagonist

Starting from acylsufonamide HTS hit 2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists. Structural modifications on lead compound 4a were explored with the aim of improving potency, physicochemical properties, and animal PK predictive of QD (once a day) dosing regimen in human. These efforts led to the discovery of the clinical candidate AAT-008 (4j), which exhibited significantly improved pharmacological profiles over grapiprant (1).     

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.     

Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia

Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia.     

右美托咪定对腰椎全麻手术患者术后疼痛及认知功能的影响

目的:探讨右美托咪定对腰椎全麻手术患者术后疼痛及认知功能的影响。方法:选择2014年3月~2015年12月在我院行腰椎全麻手术的84例患者为研究对象,按照随机数字表法分为对照组(42例)和试验组(42例),患者均常规给予芬太尼及顺式阿曲库铵麻醉诱导,试验组患者在麻醉诱导过程中给予右美托咪定静脉注射,对照组患者仅给予氯化钠注射液静脉注射。分别于术前(T0)、手术开始2 h(T2)、术后24 h(T24)检测血清肾上腺糖皮质激素,采用疼痛视觉模拟评分法(VAS)进行疼痛评定;采用简易智能精神状态量表(MMSE)于术后1d和2d进行认知状态评定,并计算术后认知功能障碍(POCD)发生率;同时观察患者不良反应发生情况。结果:试验组患者T2和T24时肾上腺糖皮质激素水平明显低于T0,T2时试验组患者肾上腺糖皮质激素水平明显低于对照组,差异有统计学意义(P0.05)。试验组患者T2时VAS评分明显低于对照组,差异有统计学意义(P0.05)。术后1d和2d时试验组患者的MMSE评分高于对照组,POCD发生率明显低于对照组;两组患者术后2d时MMSE评分高于术后1d,POCD发生率明显低于术后1d,差异均有统计学意义(P0.05)。两组患者均未见除POCD以外的不良反应。结论:右美托咪定有较强的抗氧化能力,可有效减轻腰椎全麻手术患者的疼痛程度,提高患者的认知功能。     

腰椎旁神经阻滞联合超短波对腰椎间盘突出症患者疼痛及腰背肌生物力学性能的影响

目的:探讨腰椎旁神经阻滞联合超短波对腰椎间盘突出症疼痛及腰背肌生物力学性能的影响。方法:选择我院2014年2月~2016年8月收治的98例腰椎间盘突出症患者,按抽签法分组对照组与研究组。对照组采用腰椎旁神经阻滞治疗,研究组基于对照组加用超短波治疗。观察两组的临床疗效、治疗前后视觉模拟评分(VAS)、60°/s角速、120°/s角速平均功率(AP)、峰力矩(PT)、腰背屈/伸比值(F/E)、血清P物质(SP)、β-内啡肽(β-EP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平的变化及不良反应的发生情况。结果:研究组总有效率为95.91%,显著高于对照组,差异有统计学意义(P0.05)。治疗后,两组F/E值、血清SP、IL-6、TNF-α水平均较治疗前显著降低,且研究组以上指标均明显低于对照组,两组AP、PT、血清β-EP水平均较治疗前明显上升,且研究组以上指标显著高于对照组,差异均有统计学意义(P0.05)。两组不良反应的发生率比较差异无统计学意义(P0.05)。结论:腰椎旁神经阻滞联合超短波治疗腰椎间盘突出症的效果明显优于单用腰椎旁神经阻滞治疗,其可有效缓解疼痛及改善腰背肌生物力学性能,并减轻炎症反应。