Thienorphine induces analgesia by binding κ -and δ-, or by partially binding μ-opioid receptor,thus further regulating cAMP-PKA activity

OBJECTIVE Thienorphine,a new oripavine derivative,has shown to possess stronger antinociceptive effects and better oral bioavailability compared to buprenorphine.The present study examines the effect of thienorphine on c AMP-dependent protein kinase A(PKA) activity in CHO cells expressing μ-,κ-,δ-and ORL1 receptors.In addition,we further examined its analgesic effect in vivo.METHODS The effect of thienorphine on cA MP-dependent PKA redistribution and cA MP inhibition were analyzed in CHO-PKAcatEGFP cells.PKA redistribution assays in CHO-PKAcatEGFP cells stably expressing μ-,κ-,δ-and ORL1 receptors were analyzed by high-throughput screening system to elucidate the efficacy of agonists or antagonists on opioid receptors.Moroever,the antinociceptive effects of thienorphine in vivo were examined using hot plate test.RESULTS Briefly,the maximum inhibition of thienorphine on PKA activity was about 36%,100%,100%and 12% in CHO-μ/κ/δ/ORL1-PKAcatE GFP cel s,respectively.In addition,thienorphine concentrationdependently inhibited the PKA activity with EC50 value of(22.7±18.1) nmol·L^(-1) in CHO-κ-PKAcatE GFP cels and(12.4±7.7) nmol·L^(-1) in CHO-δ-PKAcatE GFP cells.Thienorphine induced approximately 50%antinociceptive effect in mice lacking μ receptors compared to their wild-type controls(P<0.05).Also,the κ and δ selective antagonist nor-binaltorphimine,naltrindole decreased approximately 50%-60% in % MPE of theinorphine in μ-KO mice,respectively.The ORL1 receptor selective antagonist J113397 had no effect in %MPE of theinorphine in μ-KO mice.CONCLUSION Thienorphine induces analgesia through bindingκ-and δ-,or by partially binding μ-opioid receptor,thus further regulating the cAMP-PKA activity.Therefore,thienorphine may be used in acute or chronic pain with minimal addictive potential.

DN-9: a multifunctional agonist of opioid and neuropeptide FF receptors that produces nontoleranceforming analgesia via peripheral opioid receptors in inflammatory and neuropathic pain models

OBJECTIVE Considerable effort has recently been directed at developing multifunctional opioid drugs as an alternative strategy to minimize the unwanted side effects of opioid analgesics.We recently developed a novel multifunctional agonist for opioid and neuropeptide FF(NPFF) receptors named DN-9.The present study was conducted to evaluate the pharmacological activities of DN-9 after peripheral administration.METHODS Antinociceptive activities of subcutaneous DN-9 were investigated in mouse models of acute inflammatory and neuropathic pain.Furthermore,the side-effects of DN-9 were evaluated after peripheral injection in rotarod,antinociceptive tolerance,abuse and gastrointestinal transit tests.RESULTS Subcutaneous DN-9 dose-dependently produced antinociception via peripheral mu-and kappa-opioid receptors,independent of delta-opioid and NPFF receptors,in the tail-flick assay.Similarly,a dose-dependent antinociceptive effect of DN-9 was mediated via peripheral opioid receptors in other inflammatory and neuropathic pain models.Repeated treatment with DN-9 produced antinociceptive effects without a loss of potency in various models of acute,inflammatory and neuropathic pain.DN-9 maintained potent analgesia in morphine-tolerant mice.The gastrointestinal motility inhibition and abuse properties of DN-9 were significantly reduced after subcutaneous injection compared to morphine.DN-9 did not significantly influence the motor coordination of mice.CONCLUSION Subcutaneous administration of DN-9 produces potent analgesic activities with minimal side effects.These data strengthen the therapeutic potential of peripherally acting opioids with multifunctional agonistic properties that are active in a broad range of experimental pain models after peripheral delivery.

阿片类药物诱导瘙痒的机制研究进展

瘙痒是临床使用阿片类药物镇痛的患者普遍存在的严重不良反应之一。大量研究已经阐明阿片类药物的镇痛机制,但阿片类药物诱导瘙痒的机制尚不明确,瘙痒与镇痛之间的关系也模糊不清。目前的研究发现,阿片类药物作用于μ、κ及δ阿片受体后,直接或间接影响瘙痒关键受体——胃泌素释放肽受体的功能,进而影响瘙痒信息传递。神经介素B、神经肽Y、B型利钠肽等神经肽,以及其他受体如瞬时受体电位香草素1受体、N-甲基-D-天冬氨酸受体、5-羟色胺受体等,在吗啡诱导的瘙痒中也具有重要作用。 此外,阿片类药物所致瘙痒的预防和治疗也是围手术期吗啡镇痛的难点和热点之一。因此,明确瘙痒的具体发生机制,对寻找新的研究思路及预防和治疗阿片类药物诱导的瘙痒具有重要意义。

Efficacy of Perioperative Intravenous Lidocaine for Multimodal Analgesia

Given the rising incidence of opioid misuse and opioid-related deaths worldwide, it is imperative to find nonopioid analgesic adjuncts for perioperative pain management. Perioperative opioid exposure in opioid-naïve patients for even minor surgical procedures may result in significant opioid dependence. Although the use of intravenous lidocaine in the perioperative period is not novel, recently it has been proposed as an important adjunct to multimodal analgesia. In addition to improving acute pain, lidocaine may reduce the incidence of chronic post-operative pain syndrome (CPPS), improve bowel function, and decrease post-operative nausea and vomiting (PONV) thereby speeding up the post-operative recovery process. Furthermore, lidocaine has efficacy in a variety of procedures including abdominal, gynecological, and urological surgeries. The aim of this narrative review is to evaluate the effects of intravenous lidocaine compared to traditional analgesic methods on post-operative pain control and recovery for various surgical procedures.

Salient concerns in using analgesia for cancer pain among outpatients: A cluster analysis study

AIM To identify unique clusters of patients based on their concerns in using analgesia for cancer pain and predictors of the cluster membership.METHODS This was a 3-mo prospective observational study(n = 207).Patients were included if they were adults(≥ 18 years), diagnosed with solid tumors or multiple myelomas, and had at least one prescription of around the clock pain medication for cancer or cancer-treatment-related pain.Patients were recruited from two outpatient medical oncology clinics within a large health system in Philadelphia.A choice-based conjoint(CBC) analysis experiment was used to elicit analgesic treatment preferences(utilities).Patients employed trade-offs based on five analgesic attributes(percent relief from analgesics, type of analgesic, type of sideeffects, severity of side-effects, out of pocket cost).Patients were clustered based on CBC utilities using novel adaptive statistical methods.Multiple logistic regression was used to identify predictors of cluster membership.RESULTS The analyses found 4 unique clusters: Most patients made trade-offs based on the expectation of pain relief(cluster 1, 41%).For a subset, the main underlying concern was type of analgesic prescribed, i.e., opioid vs non-opioid(cluster 2, 11%) and type of analgesic side effects(cluster 4, 21%), respectively.About one in four made trade-offs based on multiple concerns simultaneously including pain relief, type of side effects, and severity of side effects(cluster 3, 27.5%).In multivariable analysis, to identify predictors of cluster membership, clinical and socioeconomic factors(education, health literacy, income, social support) rather than analgesic attitudes and beliefs were found important; only the belief, i.e., pain medications can mask changes in health or keep you from knowing what is going on in your body was found significant in predicting two of the four clusters [cluster 1(-); cluster 4(+)].CONCLUSION Most patients appear to be driven by a single salient concern in using analgesia for cancer pain.Addressing these concerns, perhaps through real time clinical assessments, may improve patients' analgesic adherence patterns and cancer pain outcomes.

Perioperative Adjunct Magnesium Decreases Postoperative Opioid Requirements—A Meta-Analysis

Objectives: Magnesium (Mg) is the fourth most common cation in the body and has numerous physiological activities and anti-nociceptive effects. The anti-nociceptive effects are primarily mediated by regulation of calcium influx into the cell and antagonism of the N-Methyl-D-aspartate glutamate receptors. Opioids are widely used as analgesics to minimize postoperative pain, but their use is associated with various side effects as well as the potential for addiction and tolerance. Systemic Mg has been proposed as an adjunct to minimize postoperative pain in numerous clinical studies. This meta-analysis aims to critically examine the ability of perioperative intravenous (IV) Mg to reduce opioid use and its’ side effects. Methods: A comprehensive literature search of Pub Med, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966-2016) was performed to identify all randomized control trials (RCTs) assessing the use of perioperative IV Mg in the reduction of postoperative opioid consumption. Keywords searched included combinations of “magnesium”, “pain”, “postoperative”, “preoperative”, “analgesia” and “opioid”. Inclusion criteria included RCTs comparing the use of perioperative IV Mg with a control group in adult patients (>18 yrs) undergoing elective surgery. Cumulative opioid consumption within the first 24 hours (hrs) postoperative period and the incidence of nausea and vomiting were analyzed. Results: 14 RCTs involving 910 patients were identified (455 patients received Mg and 455 patients received placebo or no therapy). Opioid consumption was significantly decreased in the systemic Mg group (standard mean difference [SMD]: 1.39, 95% CI 1.83 to -0.96;p p p = 0.234). Systemic Mg adjunct had no significant effect on postoperative nausea and vomiting (RR = 0.63;95% CI 0.38 to 1.04;p = 0.07). Conclusion: Perioperative IV Mg administration reduces opioid use in the first 24 hours postoperatively without any serious adverse events. The decreased need for postoperative opioids in the Mg group was not associated with a decrease in opioid-related side effects such as nausea and vomiting. Mg is an efficacious adjunct for postoperative analgesia and should be considered in multimodal analgesic treatment plans. Additional studies are required to optimize the Mg dose and timing, and to address whether specific opioids display unique benefit or resistance to adjunct Mg therapy.

Intrathecal morphine for postoperative analgesia: Current trends

The practice of anesthesiology has always been governed by evidence-based medicine. The quick turnover rate of patients in the operating room and patient safety and satisfaction, have also further changed the way we practice anesthesia. The use of intrathecal(IT) opiates as an effective form of postoperative pain relief has been established for many years. Morphine was the first opioid used by IT route. In clinical practice, morphine is regarded as the gold standard, or benchmark, of analgesics used to relieve intense pain. Perhaps for this reason, IT morphine has been used for over 100 years for pain relief. IT morphine is one of the easiest, costeffective and reliable techniques for postoperative analgesia and technical failures are rare. And yet there is no consensus amongst anesthesiologists regarding the dose of IT morphine. Like all other methods of pain relief, IT morphine also has some side effects and some of them are serious though not very common. This review article looks into some of the key aspects of the use of IT morphine for post-operative analgesia and various doses for different procedures are discussed. This article also describes the side effects of IT morphine and how to treat and prevent them.

Analgesic and anti-inflammatory potential of aerial parts of the Daphne mucronata Royle extract in mice: Opioid-independent action

Objective: To investigate the analgesic and anti-inflammatory property and possible involvement of opioid receptors of ethyl acetate extract from aerial parts of Daphne mucronata(D. mucronata) in mice by formalin test.Methods: Single doses of 2.5, 5.0 and 10.0 mg/kg of body weight of ethyl acetate extract of D. mucronata were intraperitoneally administered to the mice 30 min before analgesic test. The anti-nociceptive effect of preparations was evaluated based on the formalin in mice.Results: The results indicated that the extract(2.5, 5.0 and 10.0 mg/kg) increased the pain threshold of mice and induced analgesia in both phases of formalin test. Like morphine sulfate(5.0 mg/kg, i.p.), the extract also showed more effective analgesic effect on the late phase of formalin test. Pre-treatment of animals with naloxone(5.0 mg/kg i.p.)did not inhibit the effects of the extract.Conclusions: Our findings suggest that D. mucronata contains potential analgesic and anti-inflammatory compounds which support its traditional use. Moreover, it seems that the analgesic and anti-inflammatory effects of the extract is mediated by non-opioid mechanisms. Further pharmacological studies are required to determine whether the analgesic mechanisms are actually responsible for such properties.

Endorphinergic Attenuation of Distress by Concomitantly Enhancing Endogenous Opioid Release and Switching Opioid Receptor Signaling from an Excessively Excitatory to a Normal Inhibitory Mode

The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitatory autonomic withdrawal effects in chronic opioid-dependent animals and humans, as well as to the “quasi-morphine withdrawal syndrome” evoked in naive rodents shortly after acute systemic injection of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors. These symptoms result from excessive excitatory opioid receptor signaling and increased endorphin release. Pharmacologic analyses of the remarkably plastic bimodal (excitatory/inhibitory) signaling functions of opioid receptors have utilized microelectrode recordings from opioid-sensitive neurons in tissue cultures of mouse sensory ganglia and hot-water tail-flick assays in mice. These studies led to development of specific chemical formulations that switch opioid receptor signaling from an excessively excitatory to a normal inhibitory mode. Critical combinations of cAMP-PDE inhibitors that release endorphins plus specific agents that switch opioid receptors from excitatory Gs-coupled to inhibitory Gi/Go-coupled signaling were shown to attenuate hyperalgesia and distress evoked by diverse chemical stressors in mouse tail-flick assays. Both the “quasi-morphine withdrawal syndrome” in naive rodents as well as the excitatory withdrawal effects in chronic, opioid-dependent animals and humans may be manifestations of a common Endorphinergic Distress Syndrome (EDS). We suggest that many distress symptoms are caused by EDS, a dysfunctional imbalance in the endogenous opioid system, consisting of abnormal endorphin levels, together with opioid receptors predominately in their excitatory mode. Therefore, concomitantly enhancing endogenous opioid release and switching excessive excitatory opioid receptor signaling to inhibitory signaling can attenuate these distress symptoms. Trials of a critically formulated oral preparation, containing both endorphin enhancers and opioid receptor switchers, have resulted in long-term anxiolytic efficacy and enhanced calm and mental clarity in large numbers of individuals with distress symptoms. These endorphinergic formulations may provide treatment for the emotional and physical distress associated with many psychiatric, neurologic, and neurodevelopmental disorders.

Analgesia after liver transplantation

This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation(LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intraand postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience.

A systematic Review of the Safety and Effectiveness of Epidural Analgesia for Labor Analgesia

Objective To re-evaluate the systematic review of the safety and effectiveness of epidural analgesia(EA)for labor analgesia.Methods The Cochrane database,PubMed,EMBASE,EBSCO,Web of Science,ScienceDirect,China Biomedical Literature database,CNKI,Wanfang and VIP databases were searched,and the search time was limited to August 2020.Two researchers screened the literature and extracted data according to the inclusion criteria.AMSTAR was used to evaluate the methodological quality of the included studies.Pain intensity and pain relief satisfaction were used as the main indicators for re-evaluation of the effectiveness.Midwifery rate,cesarean section rate,back pain,fever,nausea and vomiting,umbilical artery pH value,and newborn Apgar score were used as the main indicators to re-evaluate the safety.Results and Conclusion A total of 9 meta-analyses were included.The safety and effectiveness of EA and opioid intravenous analgesia,acupuncture stimulation,inhalation analgesia,no analgesia,and continuous delivery were evaluated separately.The included systematic reviews showed that EA could increase the rate of device-assisted delivery,causing maternal fever,and prolonging the first and second stages of labor.But the incidence of back pain,nausea,and vomiting was lower.Therefore,analgesia had a good effect with better satisfactory degree.Current evidence shows that EA is safe and effective for labor analgesia,but the quality of the reports of current studies is not high.

A Comparison of Local Infiltration Analgesia and PECS II Block for Analgesia in Mastectomy with Axillary Dissection—A Randomised Equivalence Study

Objective: Various analgesic techniques can be used for a mastectomy with axillary dissection with varying degrees of efficacy. In our institution, local anaesthesia infiltration (LIA) is commonly performed by surgeons. In this study, we hypothesise that the relatively novel PECS II block is equivalent to the analgesic profile of LIA. Methodology: In this single center, prospective, randomised control trial, 40 patients undergoing unilateral mastectomy with axillary dissection were randomly assigned to receive either 30 ml 0.5% ropivacaine before skin via LIA by a specialist breast surgeon during surgery or 30 ml 0.5% ropivacaine via PECS II block, before skin incision. Fentanyl was used as rescue analgesia intraoperatively, and all patients received morphine via patient-controlled analgesia (PCA) device postoperatively. The primary outcome was the difference in total morphine consumption in 24 hours between the 2 groups after surgery with equivalency set at ±1 mg. Secondary outcomes included time to rescue analgesia after block administration, post-operative pain score over 24 hours, adverse effects encountered, total intraoperative opioid usage, effect on operative time, block performance time as well as block and surgery related complications. Results: Unadjusted mean PCA morphine consumption over 24 hours post-operatively comparing local infiltration analgesia (LIA) to that of PECS II at 95% confidence interval was -1.22 mg (95% CI: -3.77, 1.33). Total IV Fentanyl use comparing LIA to PECS II was 2.53 ± 0.98 mcg/kg and 1.96 ± 0.57 mcg, P = 0.035. There were no other significant differences in the secondary outcome. Conclusion: We conclude there is a lack of equivalence between that of LIA and PECS II block, with the PECS II block providing superior analgesia.

前交叉韧带重建术后三种不同药物镇痛早期疗效的对比

目的:比较去痛片(复方氨基比林、非那西丁片,商品名去痛片)、盐酸曲马多缓释片(商品名:奇曼丁)及盐酸哌替啶(商品名:杜冷丁)在膝关节前交叉韧带自体肌腱单束重建术后早期的止疼效果及安全性。方法:回顾性分析2018年11月至2019年2月,北京大学第三医院连续收治的45例由同一组医师施行膝关节镜下前交叉韧带自体肌腱单束重建术患者,术后疼痛情况和使用药物镇痛情况的临床资料。采用随机区组设计,根据前交叉韧带断裂是否合并半月板损伤将患者分为两组,A组为单纯膝关节前交叉韧带重建的患者24例,B组为前交叉韧带断裂合并半月板损伤的患者21例。两组又根据患者实际使用的术后镇痛药物各分为3组,其中,A组口服去痛片4例、口服奇曼丁11例、肌肉注射(简称肌注)杜冷丁联合盐酸异丙嗪(商品名:非那根)9例;B组口服去痛片3例、口服奇曼丁10例、肌注杜冷丁联合非那根8例。术后早期,患者诉疼痛并主动要求镇痛时随机给予去痛片、奇曼丁或杜冷丁联合非那根这三种不同的止痛药物缓解疼痛,采用疼痛视觉模拟评分(visual analogue scale, VAS)评估疼痛缓解情况,并观察不良反应发生情况。结果:患者在性别、年龄、体重指数、住院时间等基本情况上差异无统计学意义(P>0.05)。应用三种止痛药物缓解疼痛的两组患者,在用药前及用药1 h后通过VAS评分判断结果表明,患者疼痛情况明显缓解,用药前后疼痛差异有统计学意义(P<0.05)。对两组患者应用的三种药物进行两两比较显示,杜冷丁联合非那根组对于疼痛缓解的程度显著高于其余两种药物(P<0.05),用药1 h后,两组差异无统计学意义(P>0.05)。应用杜冷丁患者易出现恶心、呕吐等副反应,但应用杜冷丁的同时使用非那根可减少副反应。在不良反应方面,仅单纯前交叉韧带重建组中应用奇曼丁组的患者出现恶心1例,其余各组患者均未出现严重的并发症及过敏反应。结论:无论是单纯交叉韧带重建,还是合并半月板成型或缝合的交叉韧带重建,患者应用去痛片、奇曼丁、杜冷丁联合非那根这三种药物均能有效缓解疼痛,其中杜冷丁对疼痛的缓解幅度最大。应用杜冷丁的同时,合用非那根可有效减轻患者的呕吐、恶心等不良反应,增加用药安全性。

The Effectiveness of Ketamine Compared to Opioid Analgesics for Management of Acute Pain in Children in the Emergency Department: Systematic Review

Background: Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to prove the efficacy of ketamine as an analgesic in children presenting in the emergency department. Objective: The first objective of this systematic review was to investigate the effectiveness of ketamine compared to opioid analgesics for pain management in children aged two months to 18 years who have acute pain in the emergency department. The second objective was to compare the adverse events and side effects associated with ketamine with those associated with opioids used for pain management. Methods: A systematic review, using the JBI systematic review was completed. A computerised search from five databases;CINAHL, EMBASE, EMCARE and PubMed, and Cochrane. The included studies were appraised by JBI critical appraisal tool for randomised controlled trials and the study results analysed. Findings: Four randomised control trial studies were included in this systematic review. All the included studies compared ketamine with opioids (morphine and fentanyl) for the management of severe pain in children. The studies were of high methodological quality based on JBI critical appraisal outcome. Meta-analysis was not possible because of the heterogeneity of the studies, especially in terms of different outcome measures, and the approaches (pain assessment tool) used to measure the pain outcomes. The review identified that ketamine demonstrated a non-inferior analgesia effect compared to opioid medication (morphine or fentanyl) as determined by various pain scores used in different studies. However, ketamine use was associated with increased frequency of occurrence of temporary adverse effects that do not require clinical attention. Conclusion: Based on the findings from the review, ketamine is a suitable alternative for opioid analgesics for the management of acute and severe pain in children in ED. The minor transient side effects associated with ketamine should not limit the use of ketamine. Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department.

硫酸镁辅助镇痛效果及在无阿片类药物麻醉方案中的应用前景

在疼痛治疗过程中为了减少阿片药物的应用,已经尝试引入辅助镇痛剂。越来越多的数据表明N-甲基-D-天冬氨酸(NMDA)受体拮抗剂可能具有增强阿片样物质的镇痛作用,诸多研究显示硫酸镁的辅助镇痛作用在疼痛治疗和围手术期麻醉方面表现出很好的应用前景。硫酸镁应用于疼痛治疗的药理学机制主要是其具有NMDA偶联通道的生理电压依赖性阻断剂的作用,其抗伤害性作用与镁阻断钙内流,从而抑制中枢敏感化并降低先前存在的痛觉过敏有关。该文综述硫酸镁在围手术期应用的现状,主要介绍硫酸镁静脉给药、鞘内给药、局部给药的辅助镇痛效果和减少阿片类药物消耗作用,以及在无阿片类药物麻醉方案中的作用及应用前景。

乳腺癌改良根治术患者近端肋间臂神经联合前锯肌平面阻滞临床效果观察

目的:探讨乳腺癌改良根治术患者近端肋间臂神经阻滞联合前锯肌平面阻滞(SAPB)的临床效果。方法:选择在全身麻醉下行乳腺癌改良根治术的患者60例,采用随机数字表法分为近端肋间臂神经阻滞联合SAPB组(联合组)和SAPB组(前锯肌组),每组30例。两组分别在全麻诱导后行超声引导下近端肋间臂神经阻滞联合前锯肌平面阻滞和前锯肌平面阻滞。采用视觉模拟评分法(VAS)记录患者术后30 min及2、4、8、24 h疼痛情况。记录术中瑞芬太尼使用总量、术后24 h舒芬太尼使用总量、补救镇痛时间、24 h内补救镇痛率以及不良反应情况。结果:与前锯肌组比较,联合组术后2、8 h的VAS评分降低,术中瑞芬太尼的使用量及术后舒芬太尼的使用量减少,总不良反应率降低,首次补救镇痛时间延长,24 h内补救镇痛率降低(均P<0.05)。结论:与前锯肌平面阻滞相比,近端肋间臂神经阻滞联合前锯肌平面阻滞可以减少围手术期阿片类药物使用,改善乳腺癌改良根治术患者术后镇痛效果。

快速康复理念下剖宫产术后多模式镇痛的研究进展

为了减少产妇术后疼痛、促进产妇术后快速恢复以及保障婴儿健康,剖宫产术后的镇痛方案一直在不断完善。其中多模式镇痛是剖宫产术后快速康复(enhanced recovery after cesarean,ERAC)的重要组成部分,做好剖宫产术后的多模式镇痛是十分必要的。为尽量减少阿片类药物的不良反应,非阿片类药物与区域阻滞的应用逐渐增多,多模式镇痛方案也在逐步完善。然而,到目前为止,关于剖宫产术后的多模式镇痛方案仍存在争议,尚无最佳方案出现。本文总结了目前剖宫产术后的多模式镇痛方案,并为多模式镇痛方案的发展提供思路。

零阿片术后自控镇痛策略在胸科腔镜手术中的应用效果

目的探讨零阿片术后自控镇痛策略在胸科腔镜肺部病损切除术中的应用效果。方法本研究为单中心、双盲前瞻性、开放性、随机对照试验。纳入2021年11月-2023年4月重庆医科大学附属第二医院在胸科腔镜下行肺部病损切除术的患者90例,依据随机数字表法分为艾司氯胺酮+右美托咪定(esKDex)组(n=30)、舒芬太尼+右美托咪定(sFDex)组(n=30)、曲马多+右美托咪定(TraDex)组(n=30)。比较3组术后48 h内恶心呕吐(PONV)的发生率、生命体征相关指标、视觉模拟评分法(VAS)评分、BCS舒适评分、Ramsay镇静评分、简易精神状态(MMSE)评分。结果术后48 h内,esKDex组PONV发生率低于sFDex组及TraDex组,差异有统计学意义[10.0%(3/30)vs.20.0%(6/30)vs.20.0%(6/30),P<0.001]。esKDex组及sFDex组术后2、4 h的VAS评分均低于TraDex组(术后2 h:P=0.001、0.001;术后4 h:P=0.027、0.024),术后24、48 h的VAS评分均高于TraDex组(术后24 h:P=0.008、0.029;术后48 h:P=0.005、0.005)。esKDex组和sFDex组术后24、48 h的BCS舒适评分均低于TraDex组(术后24 h:P=0.017、0.007;术后48 h:P=0.005、0.007)。3组术后48 h内的Ramsay镇静评分、MMSE评分差异均无统计学意义(P>0.05)。结论艾司氯胺酮联合右美托咪定的零阿片术后自控镇痛策略在满足胸科腔镜肺部病损切除术术后患者镇静镇痛前提下能降低PONV发生率。

罗哌卡因联合右美托咪定对剖宫产产妇镇痛效果、术后恢复和血清炎症因子的影响

目的:探讨罗哌卡因联合右美托咪定对剖宫产产妇镇痛效果和术后恢复的影响。方法:按镇痛方案不同,将行116例剖宫产术的产妇分为对照组与试验组,每组各58例。对照组使用罗哌卡因+舒芬太尼镇痛;试验组使用罗哌卡因+右美托咪定镇痛。分别于术后3、6、12、24、及48 h,对产妇的疼痛程度进行评估;记录产妇术后镇痛泵使用情况;记录两组产妇阻滞时效和术后恢复相关指标;检测产妇术前及术后24 h血清白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平;记录产妇术后48 h内不良反应发生情况。结果:两组术后3~48 h各时间点VAS评分、首次镇痛按压时间及术后48 h内镇痛泵按压次数差异均无统计学意义(P>0.05)。与对照组比较,试验组腰麻感觉阻滞达到最高平面经历的时间、感觉恢复时间较长(P<0.05),两组腰麻感觉阻滞起效时间无统计学差异(P>0.05)。与对照组相比,试验组首次肛门排气时间、泌乳始动时间均明显提前(P<0.05),48 h哺乳次数增多(P<0.05)。与对照组比较,试验组术后24 h血清IL-6、TNF-α水平更低(P<0.05),术后48 h内恶心呕吐发生率、皮肤瘙痒发生率更低(P<0.05)。结论:与罗哌卡因联合舒芬太尼比较,在腰硬联合麻醉中使用罗哌卡因联合右美托咪定也能够提供确切镇痛效果,且可减少不良反应,更能促进产妇术后恢复。

镇痛药物研发的潜在方向

生理状态下,疼痛是一种保护性反应,可使机体免受更严重的伤害,有利于物种生存。病理状态下,疼痛作为一种常见的疾病/症状,严重影响患者的生活质量。近年来,疼痛机制研究与镇痛药物研发取得了重要进展,但仍存在许多问题和挑战。本研究旨在系统性梳理该领域的历史经验,展望未来发展方向,以期将疼痛机制研究和镇痛药物研发工作推向更高层次。