Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain

Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.

Quasi-Static, Poiseuille Flow of Analgesics from an Elastomeric Pump: Theoretical Determination of Infusion Times and Toxicity Conditions

Background: Elastomeric pumps (elastic balls into which analgesics or antibiotics can be inserted) push medicines through a catheter to a nerve or blood vessel. Since elastomeric pumps are small and need no power source, they fit easily into a pocket during infusion, allowing patient mobility. Elastomeric pumps are widely used and widely studied experimentally, but they have well-known problems, such as maintaining reliable flow rates and avoiding toxicity or other peak-and-trough effects. Objectives: Our research objective is to develop a realistic theoretical model of an elastomeric pump, analyze its flow rates, determine its toxicity conditions, and otherwise improve its operation. We believe this is the first such theoretical model of an elastomeric pump consisting of an elastic, medicine-filled ball attached to a horizontal catheter. Method: Our method is to model the system as a quasi-Poiseuille flow driven by the pressure drop generated by the elastic sphere. We construct an engineering model of the pressure exerted by an elastic sphere and match it to a solution of the one-dimensional radial Navier-Stokes equation that describes flow through a horizontal, cylindrical tube. Results: Our results are that the model accurately reproduces flow rates obtained in clinical studies. We also discover that the flow rate has an unavoidable maximum, which we call the “toxicity bump”, when the radius of the sphere approaches its terminal, unstretched value—an effect that has been observed experimentally. Conclusions: We conclude that by choosing the properties of an elastomeric pump, the toxicity bump can be restricted to less than 10% of the earlier, relatively constant flow rate. Our model also produces a relation between the length of time that the analgesic fluid infuses and the physical properties of the fluid, of the elastomeric sphere and the tube, and of the blood vessel into which the analgesic infuses. From these, we conclude that elastomeric pumps can be designed, using our simple model, to control infusion times while avoiding toxicity effects.

Design, Synthesis of Analgesics and Anticancer of Some New Derivatives of Benzimidazole

This work, contains some new compounds from benzimidazole derivatives, which are synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting in 2-Mercapto-benzimidazole which is treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chloroacetates, chloroacetic chloride, alkyl halides) also the ethoxy carbonyl methyl thiobenzimidazole reacts with different amines. In addition to chloromethyl benzimidazole which resulted from the reaction between orthophenylene diamine and chloroacetic acid, which reacted with different amines. The synthesized compound tested as analgesics and anticancer activity the new derivatives revealed moderate, strong and very strong analgesics and moderate and strong anticancer activity.

Analgesic and anti-inflammatory activity of Cotinus coggygria Scop.extracts in vivo

Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.

Research Progresses in Effects of Analgesics and Sedatives on Intracranial Pressure of Neurointensive Care Patients

At present, there are some concerns and problems to treat neurointensive care patients by using analgesics and sedatives. Conditions of neurointensive care patients change quickly. For neurointensive care patients who cannot have auxiliary examination timely, clinicians judge intracranial conditions mainly through relevant monitoring devices and consciousness and pupil changes of patients. The use of analgesics and sedatives is limited due to worry about influences on consciousness evaluation and judgment and different degrees of inhibition on cardiovascular system and respiratory system. Common sedatives (e.g. benzodiazepines) and common analgesics (e.g. morphine, fentanyl and sufentanil) both may inhibit respiration. The specification often provides taboos for the use of drugs by patients with increase intracranial pressure (ICP) and craniocerebral injuries. Through literature review, the author analyzed influences of analgesics and sedatives on ICP of neurointensive care patients comprehensively.

Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

Gender Differences in Usage of Over-the-Counter Analgesics among Norwegian Adolescents

Introduction: Usage of over-the-counter (OTC) analgesic has increased among Norwegian adolescents since 2001. It has been noted that females tend to have a higher usage compared to males. In this paper we explore this gender difference. Data: Our dataset consists of 284,674 from Norwegian adolescents attending junior high school and high school between 2014 and 2017. Methods: The econometric approach consists of applying ordered logistic regressions with usage of OTC analgesics as the dependent variable and a dichotomous gender variable as the independent variable. Control variables include variables such as frequency of physical and mental health problems and other sociodemographic variables. Results: Gender, physical and mental health problems and various sociodemographic variables are found to have a significant effect on usage of OTC analgesics. Females are predicted to use significantly more analgesics. A large proportion of the gender difference evaporates when controlling for various other determinants. Conclusion: A considerable part of the observed gender difference in OTC analgesic usage can be traced back to differences in frequency and severity of physical and mental health problems. Part of the gender difference in usage, however remains unexplained.

Anticancer,Anti-inflammatory,Analgesic,and Anxiolytic Effects of Koumine and Their Molecular Mechanisms

Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.

Analgesic Effect of Combined Spinal-Epidural Anesthesia and its Effect on TNF-α and CRP Levels in Elderly Patients with Hip Fracture During Surgical Treatment

Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our hospital from January 2021 to December 2022 were selected and randomly divided into two groups,with 60 cases in the experimental group and 60 in the control group.The experimental group was given combined spinal-epidural anesthesia intervention measures,while the control group was given epidural anesthesia intervention measures.The analgesic effect,tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP)levels,and other observation indicators were analyzed after anesthesia intervention.Result:After the intervention,the analgesic effect and the evaluation results of the subjects in the experimental group were better than those in the control group(P<0.05);the obtained values of TNF-αand CRP levels in the experimental group were higher than those of the control group(P<0.05).Conclusion:The combined spinal-epidural anesthesia intervention demonstrated positive outcomes.The analgesic effect of patients during surgery and their inflammatory factor levels improved,which makes this intervention worthy of clinical application and promotion.

Synthesis and analgesic activities studies on bispiperazinium (BPZ) salts

Selecting compound 97-9-G4 as lead compound, a series of bispiperazinittm salts 5a-h were designed, synthesized and evaluated for their analgesic activities. The results show that phenylethyl group of 97-9-G4 is a crucial pharmacophore; the intro- duction of electron-withdrawing group on benzene ring is favorable to the activity.

经皮穴位电刺激对全膝关节置换术后镇痛药物用量及其不良反应的影响

目的探究经皮穴位电刺激减少全膝关节置换术后镇痛药物用量的有效性及安全性。方法采用随机数字表法将124例行单侧全膝关节置换术患者分为干预组和常规组各62例。2组患者均应用术后常规镇痛方案;干预组于术后1~7 d加用经皮穴位电刺激,30 min/次,2次/d。分析2组术后静脉自控镇痛泵的追加次数和阿片类镇痛药用量,以及2组不良事件、实验室检查[白细胞(WBC)、血小板(PLT)、血肌酐(SCr)、血尿素氮(BUN)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]结果。结果干预组术后静脉自控镇痛泵的追加次数和阿片类镇痛药物用量均低于常规组(P<0.05);干预组术后恶心症状发生率低于常规组(P<0.05),2组其他不良反应发生率比较差异无统计学意义(P>0.05);2组患者术前及术后1、7 d的实验室检查(WBC、PLT、SCr、BUN、ALT、AST)结果比较差异无统计学意义(P>0.05)。结论经皮穴位电刺激可以减少全膝关节置换术后镇痛药物用量,减少镇痛药物应用后的部分不良反应,且安全性较好。

竖脊肌平面阻滞联合星状神经节阻滞在老年腹腔镜全子宫切除术中的应用效果

目的探究竖脊肌平面阻滞(ESPB)联合星状神经节阻滞(SGB)在老年腹腔镜全子宫切除术(LTH)中的应用效果。方法选取连云港市妇幼保健院2021—2023年收治的116例行LTH的老年病人,采用随机数表法分成2组,每组58例。在麻醉诱导前,对照组予以ESPB,联合组予以ESPB联合SGB。比较2组手术指标、麻醉药物用量、VAS评分、补救镇痛情况、术后恢复、应激指标、不良反应情况及麻醉诱导前(T0)、麻醉后5 min(T1)、术毕(T2)时刻的心率(HR)和平均动脉压(MAP)。结果2组手术时间、术中出血量、术后首次下床时间、住院时间及不良反应发生率差异均无统计学意义(P>0.05);联合组丙泊酚、舒芬太尼用量及镇痛泵按压次数、补救镇痛率、术后首次排气时间均低于对照组(P<0.05)。术后6、12、24 h,2组VAS评分均逐渐下降,且联合组低于对照组(P<0.05)。2组T1、T2时刻MAP、HR水平均较T0时刻升高,T2时刻较T1时刻下降,但联合组T1、T2时刻MAP、HR水平均低于对照组(P<0.05)。术后2组皮质醇(Cor)、P物质(SP)水平均高于术前,但联合组低于对照组(P<0.05)。结论行LTH的老年病人应用ESPB联合SGB可有效提升镇痛效果,减少镇痛药物用量,维持血流动力学稳定,减轻应激反应,且安全可靠。

蛛网膜下腔阻滞麻醉联合右美托咪定对股骨颈骨折手术患者的影响

目的探讨蛛网膜下腔阻滞麻醉联合右美托咪定对股骨颈骨折手术患者的影响。方法选取2020年8月—2023年8月于西安市中医医院行股骨颈骨折手术的80例股骨颈骨折患者,采用摸球法分组,奇数为对照组,偶数为观察组,每组40例。对照组予以蛛网膜下腔阻滞麻醉+生理盐水;观察组予以蛛网膜下腔阻滞麻醉+右美托咪定。比较两组不同时点的血流动力学[麻醉前(T_(0))、术中1 min(T_(1))、术后1 min(T_(2))的心率(HR)、平均动脉压(MAP)],术后2、4、8、12 h的视觉模拟评分法(VAS)和Ramsay镇静评分(RSS),术前、术后的应激反应[肾上腺素(AD)、皮质醇(Cor)]水平,以及两组不良反应发生情况。结果两组T_(0)、T_(1)、T_(2)时的HR、MAP水平比较,结果:①不同时间点HR、MAP水平比较,差异有统计学意义(P<0.05);②观察组与对照组HR、MAP水平比较,差异有统计学意义(P<0.05),观察组HR、MAP水平较低,相对血流动力学较稳定;③两组HR、MAP水平变化趋势比较,差异有统计学意义(P<0.05)。两组术后2、4、8、12 h的静息状态下VAS评分比较,结果:①不同时间点VAS评分比较,差异有统计学意义(P<0.05);②观察组与对照组VAS评分比较,差异有统计学意义(P<0.05),观察组VAS评分较低,相对镇痛效果较好;③两组VAS评分变化趋势比较,差异无统计学意义(P>0.05)。两组术后2、4、8、12 h的RSS评分比较,结果:①不同时间点RSS评分比较,差异有统计学意义(P<0.05);②观察组与对照组RSS评分比较,差异有统计学意义(P<0.05),观察组RSS评分较高,相对镇静效果较好;③两组RSS评分变化趋势比较,差异无统计学意义(P>0.05)。观察组术前、术后AD、Cor水平差值低于对照组(P<0.05);两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论蛛网膜下腔阻滞麻醉联合右美托咪定可以有效稳定股骨颈骨折手术患者的术中及术后HR、MAP水平,降低疼痛程度,提高镇静效果,降低应激反应水平,且不增加不良反应发生率,表明其对股骨颈骨折手术患者的镇痛效果有显著提升。

不同剂量布托啡诺复合硬膜外分娩镇痛对产妇产程及镇痛效果的影响

目的探讨不同剂量布托啡诺复合硬膜外分娩镇痛对产妇产程及镇痛效果的影响。方法选取2022年10月—2023年10月常州市妇幼保健院分娩的188例产妇作为研究对象,通过随机数字表法分为4组:A组使用9.75 mL 0.125%罗哌卡因+0.25 mL布托啡诺,B组使用9.50 mL 0.125%罗哌卡因+0.50 mL布托啡诺,C组使用9.00 mL 0.125%罗哌卡因+1.00 mL布托啡诺,D组使用8.5 mL 0.125%罗哌卡因+1.5 mL布托啡诺,各47例。主要观察指标包括不同时间节点疼痛程度、镇痛效果、产程、Bromage评分、新生儿Apgar评分、镇痛效果以及并发症情况。结果各组镇痛前、镇痛后10 min、镇痛后30 min视觉模拟评分法(VAS)比较,结果:①不同时间点VAS评分比较,差异有统计学意义(P<0.05);②各组VAS评分比较,差异有统计学意义(P<0.05);③各组VAS评分变化趋势比较,差异有统计学意义(P<0.05)。各组镇痛起效时间依次缩短(P<0.05),自控镇痛(PCA)按压次数依次减少(P<0.05),首次PCA时间依次延长(P<0.05)。各组第一产程时间依次缩短(P<0.05)。各组第二、三产程时间比较,差异均无统计学意义(P>0.05)。各组镇痛30 min、胎儿分娩时的Bromage评分比较,结果:①不同时间点Bromage评分比较,差异有统计学意义(P<0.05);②各组Bromage评分比较,差异无统计学意义(P>0.05);③各组Bromage评分变化趋势比较,差异无统计学意义(P>0.05)。各组出生后1min、出生后5 min的Apgar评分比较,结果:①不同时间点Apgar评分比较,差异无统计学意义(P>0.05);②各组Apgar评分比较,差异无统计学意义(P>0.05);③各组Apgar评分变化趋势比较,差异无统计学意义((P>0.05)。各组不良事件总发生率比较,差异有统计学意义(P<0.05)。结论9.00 mL 0.125%罗哌卡因+1.00 mL布托啡诺的组合能有效降低产妇疼痛程度,缩短产程,保证分娩镇痛方式的安全有效,值得临床推广。

吗啡作为佐剂行前路腰方肌阻滞对腹腔镜子宫肌瘤剥除患者术后镇痛效果的影响

目的评估吗啡作为佐剂行前路腰方肌阻滞对腹腔镜子宫肌瘤剥除患者术后镇痛效果的影响。方法选取2021年1月至2023年12月在江苏大学附属医院行腹腔镜子宫肌瘤剥除术的患者200例为研究对象,使用随机数字表法将其分为对照组(接受超声引导的前路腰方肌阻滞,每侧给予0.375%罗哌卡因20 ml)和佐剂组(在对照组基础上添加佐剂吗啡)。比较两组麻醉前、切皮时、肌瘤剥除时、术毕的心率(HR)和平均动脉压(MAP);比较两组丙泊酚、瑞芬太尼用药量;比较两组术后48 h内静脉自控镇痛泵首次按压时间、有效按压次数;比较两组离开恢复室,术后4、24、48 h数字评分量表(NRS)评分;观察两组不良反应发生情况。结果两组各时间点组内及组间HR、MAP比较,差异无统计学意义(P>0.05)。两组丙泊酚和瑞芬太尼用药量比较,差异无统计学意义(P>0.05)。两组唤醒至睁眼时间、气管导管拔除时间、恢复室停留时间、麻醉苏醒期躁动发生率比较,差异无统计学意义(P>0.05)。佐剂组镇痛泵首次按压时间长于对照组,有效按压次数少于对照组(P<0.05)。术后4、24、48 h,佐剂组NRS评分低于对照组(P<0.05)。两组均未发生心动过缓、低血压、尿潴留。两组恶心、呕吐、头晕、皮肤瘙痒发生率比较,差异无统计学意义(P>0.05)。结论罗哌卡因中添加佐剂吗啡行前路腰方肌阻滞可增强腹腔镜子宫肌瘤剥除术后的镇痛效果且安全性良好。

姜味草化学成分、药理活性、临床应用研究进展及质量标志物预测分析

作为一种药食同源的中药材,在我国西南地区,姜味草被广泛用作食品香料和理气药。其化学成分类型丰富,药理作用广泛。现代研究表明,姜味草富含大量挥发油类、黄酮类、有机酸类、甾醇类和三萜类等成分,具有抗炎、镇痛、抗肿瘤、抗微生物和抗氧化等药理作用。通过系统总结国内外文献,对姜味草的化学成分、药理作用及临床应用进行分析,并基于传统药性、功效、特有性、可测性及药动学原理对姜味草质量标志物进行预测,初步拟定橙花醛、香叶醛、乙酸香叶酯、齐墩果酸、熊果酸、咖啡酸、迷迭香酸和阿魏酸作为姜味草的质量标志物候选成分,以期建立姜味草质量评价,为后续深入研究提供理论依据。

Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome

AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.

某院骨科围术期镇痛药物使用情况及合理性评价

目的规范围术期镇痛药物的临床合理使用。方法采用回顾性分析方法,随机抽取某院骨科2023年1月至12月围术期使用镇痛药物的500份病历,涉及患者500例,收集患者的基本信息、围术期镇痛药物使用情况、用药后的有效性及安全性,并根据相关指南、共识、药品说明书评价其用药合理性。结果共253例患者存在313例次用药不合理情况,主要包括遴选药物不适宜(15.02%)、用法用量不适宜(50.80%)、联合用药不适宜(27.48%)及总体用药方案不合理(6.71%)。结论该院还存在围术期镇痛药物使用不合理情况,应加强其规范、合理应用。

Analgesic and anti-inflammatory activities of Passiflora foetida L.

Objective:To investigate the analgesic and anti-inflammatory activities of ethanol extract of Passiflora foetida(P.foetida) leaves.Methods:Ethanol extract of P.foetida leaf was evaluated for analgesic action by acetic acid-induced writhing and hot plate method in albino mice.The anti-inflammatory property of ethanolic leaf extract was tested by carrageenan induced acute paw edema and histamine induced acute paw edema in rats.Results:The dose 200 mg/kg of P. foetida leaf extract exhibited highest significant analgesic activity[(13.50±0.43) min]at a reaction time of 20 min in hot plate method in mice.The ethanol extract of leaf dose 100 mg/kg produced a highly significant anti inflammatory effect[(1.302±0.079) mL]in rats.Conclusions:It is very clear that P.foetida also has analgesic and anti-inflammatory activities for the pharmaceuticals.

Analgesic,anti-inflammatory and anti-diarrheal activities of ethanolic leaf extract of Typhonium trilobatum L.Schott

Objective:To explore the efficacy of ethanolic leaf extract of Typhonium trilobatum L.Schott in treating diarrhea,pain and inflammation using experimental models.Methods:In the present study,acetic acid-induced writhing,xylene-induced ear edema and castor oil-imluced diarrlieal model were used to evaluate the analgesic,anti-inflammatory and anti-diarrheal activities,respectively.Acute toxicity test was carried out to fix the safe doses of the plant extract.Results:The plant extract demonstrated a significant inhibition of writhing(P<0.01)compared with the control group in acetic acid-induced writhing test in mice.The extract also significantly inhibited the xylene induced ear edema formation(P<0.05).In anti-diarrheal test,the extract significantly decreased the frequency of defecation and increased the mean latent period(P<0.0l)in castor oil-induced diarrheal model mice at the doses of 250 and 500 mg/kg body weight.Conclusions:These results suggest that the extract possesses significant analgesic,anti-inflammatory and anti-diarrheal activities that support to the ethnopharmacologicl uses of this plant.