Appendectomy in rabbits with extended unilateral anesthesia.

Thoracic paravertebral anesthesia was not believed to accompany numbness in the lumbar nerve region. However, we recently discovered that thoracic paravertebral anesthesia could produce analgesia in the lumbar region. We called this block extended unilateral anesthesia. In this study, appendectomy was attempted in rabbits with extended unilateral anesthesia. After a catheter was inserted into the endothoracic fascia in the paravertebral region on the right side at the level of the 11th thoracic vertebra, a 3-ml dose of 2% mepivacaine was injected repeatedly through the catheter. After an injection of the local anesthetic we could observe motor and sensory paralysis unilaterally from the chest down to the lower limb in all the rabbits, the extended unilateral anesthesia. With this anesthesia, we could accomplish appendectomy. This is the initial report of extended unilateral anesthesia applied to appendectomy in rabbits. We think that this anesthesia could be beneficial in future medical and veterinary use.     

A Comparison of the Analgesia Efficacy and Side Effects of Paravertebral Compared with Epidural Blockade for Thoracotomy: An Updated Meta-Analysis

Objective

The most recent systematic review and meta-analysis comparing the analgesic efficacy and side effects of paravertebral and epidural blockade for thoracotomy was published in 2006. Nine well-designed randomized trials with controversial results have been published since then. The present report constitutes an updated meta-analysis of this issue.

Summary of Background

Thoracotomy is a major surgical procedure and is associated with severe postoperative pain. Epidural analgesia is the gold standard for post-thoracotomy pain management, but has its limitations and contraindications, and paravertebral blockade is increasingly popular. However, it has not been decided whether the analgesic effect of the two methods is comparable, or whether paravertebral blockade leads to a lower incidence of adverse side effects after thoracotomy.

Methods

Two reviewers independently searched the databases PubMed, EMBASE, and the Cochrane Library (last performed on 1 February, 2013) for reports of studies comparing post-thoracotomy epidural analgesia and paravertebral blockade. The same individuals independently extracted data from the appropriate studies.

Result

Eighteen trials involving 777 patients were included in the current analysis. There was no significant difference in pain scores between paravertebral blockade and epidural analgesia at 4–8, 24, 48 hours, and the rates of pulmonary complications and morphine usage during the first 24 hours were also similar. However, paravertebral blockade was better than epidural analgesia in reducing the incidence of urinary retention (p<0.0001), nausea and vomiting (p = 0.01), hypotension (p<0.00001), and rates of failed block were lower in the paravertebral blockade group (p = 0.01).

Conclusions

This meta-analysis showed that PVB can provide comparable pain relief to traditional EPI, and may have a better side-effect profile for pain relief after thoracic surgery. Further high-powered randomized trials are to need to determine whether PVB truly offers any advantages over EPI.     

胸椎旁神经阻滞复合全身麻醉对胸腔镜肺癌根治术患者镇痛效果及血生化指标的影响

目的:探讨胸腔镜肺癌根治术患者应用胸椎旁神经阻滞复合全身麻醉后,对其镇痛效果、T淋巴细胞亚群以及血清肿瘤标志物的影响。方法:选取青海红十字医院于2015年9月~2018年10月期间接收的131例行胸腔镜肺癌根治术患者。采用随机数字表法将患者分为对照组(n=65)和研究组(n=66),对照组给予全身麻醉,研究组在对照组基础上复合胸椎旁神经阻滞,比较两组患者镇痛效果、自控静脉镇痛(PCIA)自控按钮启动次数、背景输注总量、T淋巴细胞亚群、血清肿瘤标志物以及不良反应。结果:研究组术后2h、12h、24h、48h安静时以及咳嗽时视觉疼痛模拟评分(VAS)均低于对照组(P<0.05);研究组术后24h、术后48h PCIA自控按钮启动次数、背景输注总量均低于对照组(P<0.05);研究组术后24h、术后48h、术后72h CD3^+、CD4^+、CD4^+/CD8^+均高于对照组(P<0.05);研究组术后24h癌胚抗原(CEA)、糖抗原199(CA199)、糖抗原125(CA125)水平均低于术前,且低于对照组(P<0.05);研究组不良反应总发生率低于对照组(P<0.05)。结论:胸椎旁神经阻滞复合全身麻醉应用于胸腔镜肺癌根治术患者,镇痛效果确切,可有效改善机体免疫功能,降低血清肿瘤标志物水平,安全可靠。     

患者静脉自控镇痛与患者硬膜外自控镇痛的比较

术后自控镇痛方法有：患者静脉自控镇痛（Patient-controlled Intravenous Analgesia, PCIA）、患者硬膜外自控镇痛 (Patient-controlled Epidural Analgesia, PCEA）、患者区域自控镇痛（Patient-controlled Regional Analgesia, PCRA)、患者皮下自控镇痛 (Patient-controlled Subcutaneous Analgesia, PCSA)、患者自控鼻内镇痛（Patient-controlled intranasal analgesia, PCINA)、芬太尼HCI 电离子渗入疗法经皮系统（Fentanyl Iontophoretic Transdermal System, ITS)和连续椎旁阻滞（Continuous Paravertebral block, CPVB） 等。目前在临床工作中较常使用的主要是PCIA 和PCEA。有研究报道,与PCIA 比较,PCEA 镇痛效果更确切,恶心、呕吐及嗜睡发 生率低;但也有报道认为,与PCEA 相比,PCIA 实施相对方便,同时也可以提供令患者满意的镇痛效果,适用范围更广。目前对于 这两种镇痛方法的效果优劣尚无确切的定论,在此就PCIA 和PCEA的镇痛药物特点、镇痛效果、副反应及对免疫功能和肿瘤患 者远期生存率的影响作一综述。     

对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响

摘要 目的：对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响。方法：选择西安交通大学第一附属医院2020年6月至2021年12月收治的脊柱骨折患者96例作为研究对象,根据1:1随机数字表法把患者分为椎旁神经阻滞组与肋间神经阻滞组各48例。所有患者均给予脊柱手术治疗,所有手术操作都由同一组医生完成,椎旁神经阻滞组与肋间神经阻滞组分别给予超声引导下椎旁神经阻滞与肋间神经阻滞,记录两组阻滞效果及对血流动力学的影响。结果：两组通气5 min、通气30 min、恢复双肺通气30 min等时间点的HR、SPO₂值在组内与组间对比无差异（P>0.05）。两组的术中补液量、术中出血量、手术时间、麻醉时间、术中尿量等对比无差异（P>0.05）。椎旁神经阻滞组的坐骨神经运动神经、感觉神经阻滞持续时间都少于肋间神经阻滞组（P<0.05）,两组运动神经、感觉神经阻滞起效时间对比无差异（P>0.05）。椎旁神经阻滞组术后7 d的肺部感染、肺栓塞、呼吸衰竭等肺部并发症发生率2.1 %,低于肋间神经阻滞组的16.7 %（P<0.05）。结论：相对于肋间神经阻滞,超声引导下椎旁神经阻滞在脊柱手术患者并不会影响患者的血流动力学状况,也不会影响手术与麻醉过程,还可缩短坐骨神经运动神经、感觉神经阻滞持续时间,减少术后并发症的发生。     

Fine needle aspiration biopsy of vertebral and paravertebral lesions: retrospective study of 124 cases

OBJECTIVE: To evaluate the diagnostic value of image-guided fine needle aspiration biopsy (FNAB) in the diagnosis and management of vertebral and paravertebral lesions and to review similar studies in the literature. STUDY DESIGN: One hundred twenty-four FNAB cases (113 [corrected] patients) of vertebral and paravertebral lesions occurring over a 10-year period were retrieved from the archives of the University of Mississippi Medical Center for review and clinico-radiologic correlation. Thirty-four of the cases included a concurrent core needle biopsy sample, 15 cases had subsequent surgical specimens, while 32 cases had previously established malignancy. The age range was 11 days to 91 years (mean, 46 years), with 57 male patients and 56 female. RESULTS: One hundred five cases were vertebral lesions, and 19 cases were paravertebral lesions. FNAB diagnosis were malignant in 33.87% of cases, benign in 5.64%, suspicious in 4.03%, infectious/inflammatory and degenerative in 12.91%, unsatisfactory in 16.13% and negative in 27.42%. The overall sensitivity of the procedure was 89.3% and the specificity, 93.8%. The positive predictive value was 95.7% and negative predictive value, 85.2%. CONCLUSION: FNAB is an effective means of establishing a definitive diagnosis of vertebral and paravertebral lesions, allowing appropriate patient management. Cell blocks, core biopsies and ancillary studies are useful adjuncts in rendering the diagnosis.     

局麻药连续伤口输注技术在临床术后镇痛中应用的研究进展

局麻药连续伤口输注技术是区域阻滞的一种,其从源头上阻滞了切口伤害性刺激信号的发生与传导。作为新一代的术后镇痛方式,它通过一种与神经周围或切口中插管相连的弹力球囊或便携式电子泵实施患者自我控制式区域镇痛。与传统的术后镇痛方式相比,它可安全有效便捷的用于临床术后镇痛,又可避免硬膜外穿刺置管的风险,还能减少阿片类药物的应用,因而在安全镇痛和加速康复方面更有优势。本文就局麻药连续伤口输注技术的应用作以下综述,为临床术后多模式镇痛提供参考。     

Electroacupuncture analgesia could be mediated by at least two pain-relieving mechanisms; endorphin and non-endorphin systems.

This present paper shows different levels of electroacupuncture analgesia (antinociceptive effect) induced by three different frequencies of stimulation (i.e. 0.2, 4 and 200 Hz); highest analgesia is induced at 200 Hz and lowest at 0.2 Hz. Naloxone (1 mg/kg) completely reverses the electroacupuncture effects at low frequency stimulation (4 Hz) but produces no inhibition at high frequency stimulation (200 Hz). Conversely, parachlorophenylalanine (320 mg/kg) partially blocks the high-frequency (200 Hz) analgesia but produces no effect on the low-frequency (4 Hz) electroacupuncture analgesia. This suggests that electroacupuncture analgesia induced by low frequency stimulation may be mediated by endorphins while high frequency stimulation is not endorphinergic but may be partly due to serotonin.     

Cimetidine does not change the effect of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) on the opiate form of footshock-induced analgesia.

It has been demonstrated that cimetidine blocks the effect of naloxone on footshock-induced analgesia. To study the effect of cimetidine on the antiopiate properties of an endogenous peptide Tyr-MIF-1, the opiate form of intermittent footshock-induced analgesia was elicited in the rat. The nociceptive responses were determined using the hot-plate test (52.5 degrees C). Intraperitoneal pretreatment with cimetidine (100 mg/kg) or chlorpheniramine maleate (20 mg/kg) did not affect the footshock-induced analgesia, and did not change the antagonizing effect of Tyr-MIF-1 (0.2 mg/kg) on this model of antinociception. It is concluded that cimetidine and chlorpheniramine maleate do not change the antagonizing effect of Tyr-MIF-1 on the opiate form of intermittent footshock-induced analgesia.     

Tolerance to morphine in the rat: its prevention by naloxone.

Development of tolerance after a single injection of morphine in the Wistar-Lewis rat can be estimated by the attenuation of the response to a second injection of morphine given three days later. If naloxone is given 35 minutes after the first morphine injection and after the appearance of measurable analgesia, attenuation of the effects of the second morphine injection is not seen. It appears that naloxone blocks the development of tolerance to morphine even if given after the morphine-receptor interaction responsible for analgesia has been initiated. The temporal relationship between the prior injection of morphine and the subsequent administration of naloxone is being explored.     

超声引导下竖脊肌平面阻滞与胸椎旁神经阻滞用于乳腺癌根治术术后镇痛效果的比较

摘要 目的：比较超声引导下竖脊肌平面阻滞（ESPB）和胸椎旁神经阻滞（TPVB）用于乳腺癌根治术术后镇痛的效果。方法：2015年5月至2019年12月在山西医科大学第二医院接受乳腺癌根治术的64例患者,随机数字表法分为ESPB组和TPVB组,每组32例。在常规全身麻醉基础上,ESPB组行ESPB,TPVB组行TPVB,术后给予患者自控静脉镇痛（PCIA）。比较两组术后2、6、12、24、48 h静息与咳嗽时视觉模拟评分（VAS）评分;比较两组患者术后PCIA首次按压时间,术后24 h PCIA镇痛泵按压次数、PCIA舒芬太尼用量,补救镇痛以及不良反应的发生率。结果：两组患者术后各时间点静息和咳嗽时VAS 评分间差异无统计学意义（P>0.05）;两组患者术后PCIA首次按压时间、术后24 h PCIA舒芬太尼用量以及补救镇痛的发生率间差异无统计学意义（P>0.05）;ESPB组患者术后24 h PCIA镇痛泵按压次数低于TPVB组,差异有统计学意义（P<0.05）;ESPB组和TPVB组术后恶心呕吐、皮肤瘙痒、呼吸抑制和头晕的发生率显比较差异无统计学意义（P>0.05）。结论：超声引导下ESPB相较于TPVB用于乳腺癌根治患者术后镇痛效果相似,且不会增加不良反应的发生率,安全性较高,可替代TPVB为乳腺癌根治术患者提供良好的术后镇痛。     

Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors

Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far nothing is known about the nonopioid component. Here we show that the specific CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716) blocks nonopioid placebo analgesic responses but has no effect on opioid placebo responses. These findings suggest that the endocannabinoid system has a pivotal role in placebo analgesia in some circumstances when the opioid system is not involved.     

Comparison of Transversus Abdominis Plane Infiltration with Liposomal Bupivacaine versus Continuous Epidural Analgesia versus Intravenous Opioid Analgesia

Epidural analgesia is considered the standard of care but cannot be provided to all patients Liposomal bupivacaine has been approved for field blocks such as transversus abdominis plane (TAP) blocks but has not been clinically compared against other modalities. In this retrospective propensity matched cohort study we thus tested the primary hypothesis that TAP infiltration are noninferior (not worse) to continuous epidural analgesia and superior (better) to intravenous opioid analgesia in patients recovering from major lower abdominal surgery. 318 patients were propensity matched on 18 potential factors among three groups (106 per group): 1) TAP infiltration with bupivacaine liposome; 2) continuous Epidural analgesia with plain bupivacaine; and; 3) intravenous patient-controlled analgesia (IV PCA). We claimed TAP noninferior (not worse) over Epidural if TAP was noninferior (not worse) on total morphine-equivalent opioid and time-weighted average pain score (10-point scale) within first 72 hours after surgery with noninferiority deltas of 1 (10-point scale) for pain and an increase less of 20% in the mean morphine equivalent opioid consumption. We claimed TAP or Epidural groups superior (better) over IV PCA if TAP or Epidural was superior on opioid consumption and at least noninferior on pain outcome. Multivariable linear regressions within the propensity-matched cohorts were used to model total morphine-equivalent opioid dose and time-weighted average pain score within first 72 hours after surgery; joint hypothesis framework was used for formal testing. TAP infiltration were noninferior to Epidural on both primary outcomes (p<0.001). TAP infiltration were noninferior to IV PCA on pain scores (p = 0.001) but we did not find superiority on opioid consumption (p = 0.37). We did not find noninferiority of Epidural over IV PCA on pain scores (P = 0.13) and nor did we find superiority on opioid consumption (P = 0.98). TAP infiltration with liposomal bupivacaine and continuous epidural analgesia were similar in terms of pain and opioid consumption, and not worse in pain compared with IV PCA. TAP infiltrations might be a reasonable alternative to epidural analgesia in abdominal surgical patients. A large randomized trial comparing these techniques is justified.     

Potentiation of foot shock analgesia by thyrotropin releasing hormone

Thyrotropin releasing hormone (TRH) interacts with both opioid and non-opioid systems in mediating hypothermic, hypoactive, cataleptic, respiratory and analgesic effects. While TRH neither antagonizes opioid analgesia nor alters pain thresholds itself, it blocks neurotensin analgesia. Different forms of pain-inhibition in rats can be activated by selectively altering the parameters of shock: while analgesia induced by 20 inescapable tail-shocks is not reversed by naltrexone, exposure to 60 or 80 shocks does elicit naltrexone-reversible analgesia. The first experiment examined whether intracerebroventricular administration of TRH (0, 10, or 50 micrograms) would alter the elevations in tail-flick latencies in rats induced by 20 or 80 foot shocks and found that TRH significantly lengthened the duration and magnitude of analgesia induced by 20 and 80 foot shocks in a dose-dependent manner. The second experiment extended these findings to the writhing test, a visceral pain test. While the number and duration of writhes of vehicle-treated rats exposed to 80 foot shocks failed to differ from baseline values. TRH (50 micrograms)-treated rats exposed to 80 foot shocks displayed significant decreases in the number and duration of writhes. The third experiment indicated that the differential effects of naltrexone upon analgesia induced by 20 or 80 tail shocks were not apparent when foot shocks were employed, precluding a definitive statement that TRH may be involved in the modulation of both opioid and non-opioid forms of analgesia.     

Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized,Controlled, Single-Center Trial

Objectives

The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery.

Methods

Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests.

Results

Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions.

Conclusions

The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery.

Trial Registration

ClinicalTrial.gov NCT00418457     

Comparison of naloxonazine and beta-funaltrexamine antagonism of mu 1 and mu 2 opioid actions.

beta-Funaltrexamine (beta-FNA) irreversibly blocks morphine analgesia, lethality and its inhibition of gastrointestinal transit, confirming that these actions involve mu receptors. In dose-response studies, beta-FNA antagonized all the actions with similar potencies (ID50 values of 12.1, 11.3 and 12.3 mg/kg, respectively). beta-FNA also reduced intra-cerebroventricular and intrathecal DAMGO analgesia equally well (ID50 values of 6.09 and 7.7 mg/kg, respectively). Naloxanazine blocked systemic morphine analgesia (ID50 value 9.5 mg/kg) and supraspinal DAMGO analgesia (ID50 value 6.1 mg/kg) as potently as beta-FNA. However, against spinal DAMGO analgesia, morphine's inhibition of gastro-intestinal transit or lethality, naloxonazine (ID50 values 38.8, 40.7 and 40.9 mg/kg, respectively) was significantly less active than beta-FNA (p less than 0.05). beta-FNA remains a valuable tool in the classification of mu opioid actions. Within the mu category, actions can be defined as either mu 1 (naloxonazine-sensitive) or mu 2 (naloxonazine-insensitive).     

全麻联合椎旁神经阻滞在胸腔镜下肺叶切除术中的麻醉效果及对术后认知功能和炎症反应的影响

摘要 目的：研究全身麻醉联合椎旁神经阻滞在胸腔镜下肺叶切除术患者的应用效果,探讨其对患者术后认知功能和炎 症反应的影响。方法：选取2017年-2021年在我院接受胸腔镜下肺叶切除术治疗的患者100例,根据其麻醉方式的不同分为对照组（50例）和研究组（50例）,对照组给予全身麻醉,研究组给予全身麻醉联合椎旁神经阻滞。比较两组患者手术时间、麻醉时间、术中出血量、舒芬太尼和瑞芬太尼用量、术后疼痛情况、简易智力状态检查量表（MMSE）评分和血清C-反应蛋白（CRP）、白介素-6（IL-6）水平。结果：两组患者手术时间、麻醉时间和术中出血量比较无显著差异（P>0.05）,而研究组患者舒芬太尼用量和瑞芬太尼用量均低于对照组（P<0.05）;研究组患者术后6、12、24和48小时疼痛评分均较对照组患者低（P<0.05）;两组患者术前MMSE评分无差异（P>0.05）,研究组患者术后6、12、24和48小时MMSE评分均较对照组高（P<0.05）;两组患者术前血清CRP和IL-6水平无显著差异,但研究组患者术后24小时血清CRP和IL-6水平均显著低于对照组（P<0.05）。结论：全身麻醉联合椎旁神经阻滞用于胸腔镜下肺叶切除术患者可有效减少手术中麻醉药物用量,术后镇痛效果更好,对患者认知功能损伤更低,并且术后炎症更低。     

Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity

MuO-conotoxin MrVIB is a blocker of voltage-gated sodium channels, including TTX-sensitive and -resistant subtypes. A comprehensive characterization of this peptide has been hampered by the lack of sufficient synthetic material. Here, we describe the successful chemical synthesis and oxidative folding of MrVIB that has made an investigation of the pharmacological properties and therapeutic potential of the peptide feasible. We show for the first time that synthetic MrVIB blocks rat NaV1.8 sodium channels and has potent and long-lasting local anesthetic effects when tested in two pain assays in rats. Furthermore, MrVIB can block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations from rat. Our work provides the first example of analgesia produced by a conotoxin that blocks sodium channels. The emerging diversity of antinociceptive mechanisms targeted by different classes of conotoxins is discussed.     

Endogenous opioid mechanisms in the regulation of pain sensitivity and behavioral reactivity in various aversive states

Study of the effect of naloxone that blocks opiate receptors on changes in thresholds of vocalization and latent periods of motile reaction in freely-behaving rats, at leg injury, intraperitoneal introduction of algogene, and at immobilization stress allowed to estimate the involvement of endogenous opiates in regulation of pain sensitivity and motile activity. Naloxone-weakened inhibition of vocalization is accompanied by the increase in inhibition of motile responses, characteristic for visceral pain and the absence of changes at trauma and immobilization stress suggest that opiates are involved in formation of endogenous analgesia at strong visceral pain stimulation.     

Synergistic interactions between cannabinoid and opioid analgesics

Cannabinoids and opioids both produce analgesia through a G-protein-coupled mechanism that blocks the release of pain-propagating neurotransmitters in the brain and spinal cord. However, high doses of these drugs, which may be required to treat chronic, severe pain, are accompanied by undesirable side effects. Thus, a search for a better analgesic strategy led to the discovery that delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, enhances the potency of opioids such as morphine in animal models. In addition, studies have determined that the analgesic effect of THC is, at least in part, mediated through delta and kappa opioid receptors, indicating an intimate connection between cannabinoid and opioid signaling pathways in the modulation of pain perception. A host of behavioral and molecular experiments have been performed to elucidate the role of opioid receptors in cannabinoid-induced analgesia, and some of these findings are presented below. The aim of such studies is to develop a novel analgesic regimen using low dose combinations of cannabinoids and opioids to effectively treat acute and chronic pain, especially pain that may be resistant to opioids alone.