Lappaconitine (LA) is a diterpene alkaloid isolated from Aconitum species and has been used in traditional Chinese medicine as an analgesic. Previous studies have also suggested that LA exerts anti-inflammatory and immunomodulatory effects. Neuroinflammation and oxidative stress, both of which are associated with mitochondrial dysfunction and apoptosis, contribute to the development and maintenance of neuropathic pain. We hypothesized that LA may protect SH-SY5Y cells against inflammation- and apoptosis-associated injury. To investigate whether LA attenuates TNF-α-induced inflammatory injury and apoptosis in SH-SY5Y cells and to explore the potential mechanisms involved. SH-SY5Y cells were pretreated with LA (0.1 or 1 μM) for 24 h and subsequently exposed to TNF-α (10 ng/mL) for 12 h. Apoptosis, mitochondrial function, inflammatory cytokine production, and the expression of mitophagy-related proteins were assessed in LA-pretreated and non-pretreated cells. LA pretreatment (0.1 or 1 μM) reduced apoptosis in TNF-α-exposed SH-SY5Y cells, increased Bcl-2 expression, and decreased the expression of Bax, Caspase-3, and Caspase-9. LA pretreatment also suppressed NF-κB activation and reduced IL-1β and IL-6 production. In addition, LA preserved mitochondrial integrity, as indicated by maintenance of mitochondrial membrane potential, reduced cytochrome c release, and decreased ROS accumulation. The expression of the mitophagy-related proteins PINK1 and Parkin was also increased following LA pretreatment. LA attenuated TNF-α-induced inflammatory injury and apoptosis in SH-SY5Y cells. These protective effects were associated with modulation of apoptosis-related signaling, suppression of inflammatory responses, preservation of mitochondrial function, and increased expression of PINK1/Parkin-related proteins. These findings suggest that LA may exert neuroprotective effects under inflammatory conditions.

Lidocaine nebulization is noninvasive, safe, and easy to perform. However, it does not provide adequate anesthesia due to the following reasons: 1. There is a high wastage of lidocaine aerosol, with at least 70 % of the lidocaine aerosol being lost from the cannula. This loss of lidocaine results in a lower amount of inhaled lidocaine, which is insufficient to provide adequate anesthesia. 2. The commercial lidocaine preparation has a low penetrating potency. The onset of anesthesia is directly related to the amount of local anesthetic in the lipidsoluble form. However, there are only a few lipid-soluble prototypes in the commercially available lidocaine cartridges. This is because the lidocaine is purposely formulated as acidic solutions (with pH levels between 3.5 and 5.5) in order to enhance the solubility and stability of the anesthetic salts. To address these issues and improve lidocaine anesthesia potency while reducing wastage, a "Y" type cannula was used for aerosol inhalation. Additionally, 1/5 vol of 5 % sodium bicarbonate solution was added to 2 % lidocaine to enhance the pH value to 7.2. This alkalized lidocaine nebulization provides an effective topical anesthesia for bronchoscopy.

Objective In order to evaluate the role of β-adrenergic receptor in bupivacaine induced cardiac depression, contractility of bupivacaine infused ventricular myoctes was assessed by a video-based edge-detection system in the presence and absence of isoproterenol, with and without β1 adrenergic antagonist esmolol. Methods We isolated the rat ventricular myocyte by enzymatic hydrolysis.The cardiomyocytes were randomly divided into 3 groups: bupivacaine group, isoproterenol + bupivacaine group and isoproterenol + esmolol + bupivacaine group.The cells contractile function（dep v, bl % peak h and time to peak 50%） were continually monitored and recorded when the cells perfused with the solution describe above. Results Bupivacaine concentration dependently suppresses myocardial contraction function.Low-concentration bupivacaine（5.9 and 8.9 μmol/L） do not suppress myocardial contractility, however, high-concentration bupivacaine suppress myocardial contraction function.Isoproterenol enhances myocardial contractility in the presence of bupivacaine（5.9 and 8.9 μmol/L）,but inhibits cardiac contraction in the presence of high-concentration bupivacaine（13.3 μmol/L）.Isoproterenol reduced the median effective dose of bupivacaine-induced myocardial contraction failure.The EC50（95%CI） of bupivacaine was 44.9（33.9～55.4） μmol/L in bupivacaine group.The EC50（95%CI） of bupivacaine was 17.9（5.9～28.9） μmol/L in isoproterenol + bupivacaine group, and significantly lower than bupivacaine group（P＜0.05）.β1-adrenergic inhibitors can reverse the effect of Isoproterenol.Addition of esmolol enhanced EC50（95%CI） of bupivacaine from 17.9（5.9～28.9） μmol/L to 40.6（28.4～53.7） μmol/L（P＜0.05）.Bupivacaine induced contractile depression is reversible. Conclusion Bupivacaine concentration dependently and reversibly suppresses myocardial contraction function.β1-adrenergic agonists can significantly increased bupivacaine-induced cardiotoxicity in rats, and β1-adrenergic inhibitors can reverse the effect of β1-adrenergic agonists.

Herpes zoster is acute sensory neuritis induced by varicella zoster virus; the postherpetic neuralgia is just a chronic neuritis disease induced by uncontrolled acute herpetic neuritis.

Facial nerve block (injection) therapy is an effective clinical treatment method on some diseases, but this method needs to be standardized. This consensus is jointly prepared by pain experts in relevant fields in China. It summarizes and guides the indications, contraindications, operation methods and efficacy evaluation of facial nerve block (injection) therapy, in order to help clinicians for standardizing the application of this method.

Background Various cellular models were used for assessment of mitochondrial damage in cardiomyocyte, but most of them are based on silent cells without contractility. The mitochondria in cells at working should be more sensitive to toxic or reperfusion damage due to their high level mitochondrial respiration. Therefore, contracting cells can represent inotropic agent-mediated high-energy demand states. Objective To establish a cellular model to detect mitochondrial damage in cardiomyocytes at contraction. Method Freshly isolated Sprague–Dawley rat cardiomyocytes were incubated with or without bupivacaine, in the presence or absence of isoprenaline, and electrically stimulated to induce rhythmic contractions. Results Contraction under electrical field stimulation did not induce mitochondrial swelling or ROS production in DMEM; the silent cells in the presence of bupivacaine showed mild mitochondrial swelling, but contracting cells exhibited significantly higher mitochondrial swelling and increased ROS production ( P < 0.05, vs. silent cells). Isoprenaline induced a further enhancement in mitochondrial swelling and ROS production in contracting cells. Conclusions Contracting cells are more sensitive to bupivacaine toxicity and could be more accurately represent mitochondrial damage in vivo condition.

目的 探讨右美托咪定拮抗阿霉素对小鼠心脏毒性的效果及作用机制.方法 100只清洁级雄性昆明种小鼠随机分为对照组(C组)和实验组(D组)各50只,每组又各分5个亚组,均一次性腹腔注射不同剂量阿霉素.C组每天腹腔注射0.9％氯化钠注射液0.005 mL·g-1,D组每天腹腔注射右美托咪定30μg·kg-1,共10 d.记录小鼠死亡数量,采用Probit法计算阿霉素致小鼠死亡的半数致死量(median lethal dose,LD50)及95％可信区间(95％CI).注射0.9％氯化钠/右美托咪定10 d后处死存活小鼠,电镜及光镜下观察小鼠心肌细胞组织学改变,免疫组化法测定小鼠心肌细胞bax和bcl-2蛋白表达情况.结果 C组阿霉素对昆明种小鼠腹腔给药的LD50为21.17 mg·kg-1(95％CI:18.12～24.74 mg·kg-1),D组LD50为29.18 mg·kg-1(95％CI:24.90～34.18 mg·kg-1),D组LD50显著高于C组(U=15.5,P=0.002).C组心肌细胞线粒体结构损伤较D组严重,且可见自噬小体.与C组比较,D组bax表达显著降低(χ2=25.90,P=0.000),2组bcl-2表达比较差异无统计学意义(P>0.05).结论 右美托咪定可明显提高阿霉素致小鼠死亡的LD50,提高小鼠生存率,其机制可能与右美托咪定降低心肌细胞线粒体损伤、抑制bax蛋白表达有关.

The pathogenesis of pain disorders is complicated, but it always fall into the same category: pain sensory nervous system disorder. The diagnosis of pain disorder is to find the injury and the pathological change of pain sensory nervous system, and the treatment of pain disorder is repairing the damages and modulating the functional disorders system.

Facial nerve block technique can be used to treat a variety of facial nerve dysfunctional diseases. Based on the anatomy and function of the facial nerve, this expert consensus summarizes the indications, contraindications, operation methods, prevention and treatment of complications and precautions of facial nerve block, so as to provide guidance for clinicians to carry out the treatment of facial nerve block.

Lack of blood supply and nutrition is the major cause of intervertebral disc degeneration and disc herniation. Treatment for disc herniation should not only remove the protrusion, but also increase the nutrition to improve pericellular microenvironment in the disc.

The factors influencing intervertebral disc nutrient supply were reviewed and the correlation among atherosclerosis, dyslipidemia, and disc endplate permeability reduction and the disc degeneration was also summarized in this paper.

Abstract The authors have requested that this preprint be removed from Research Square.

Collagenase chemonucleolysis has been effectively used in the treatment of lumbar disc herniation in pain clinic. However its underlying mechanisms and the effectiveness had not been in-depth researched and objectively evaluated.

The diagnostic and therapeutic experiences of one chronic hepatitis B patient with hypophosphoric osteomalacia induced by low dosage oral adefovir dipivoxil for a long term were retrospectively analyzed. The patient primarily complained lumbago with gradual bilateral lower limb weakness. The patient had a history of a low dose adefovir dipivoxil orally for 6 years (10 mg/d), and manifested low blood phosphorus, high alkaline phosphatase and renal glycosuria, and abnormal function of proximal renal tubules in the examination. In view of previous medication history, adefovir dipivoxil was considered to be the cause of renal damage. Adefovir dipivoxil was replaced by entecavir dispersive tablets, and potassium, phosphorus, ossified triglyceride and other treatments were given. After that, the painful symptoms were obviously relieved and the indexes of blood phosphorus and renal glycosuria improved significantly. The experience of diagnosis and treatment for the patient were summarized and the relevant literatures were reviewed for the reference of clinicians.

One patient with serious cardiac electrical storm and with resistance to antiarrhythmic medications such as esmolol and amiodarone, was successfully treated by polarized near-infrared ray irradiation on stellate ganglion. Literature review were added.

Professor Huang indicated in the reply that trigeminal neuralgia can be divided into secondary and primary kinds. It belongs to secondary kind that there is compression to trigeminal root by cerebella vascular during medical imaging or operation. But no compression was found during operation and no other causes such as tumor compression in 3.1%-17.0% patients with typical symptom of trigeminal neuralgia. This kind of trigeminal neuralgia can be called primary trigeminal neuralgia. Therefore, trigeminal neuralgia is only a symptom, not a kind of disease. One of causes publishing my paper in the title of "Trigeminal neuralgia, where is the ectopic pacemaker? Which part of the nerve should be treated?" is that there is now a trend to seek difficult and risky method for treating trigeminal neuralgia. Since pain can be relieved with peripheral nerve block or damage method, why do not we treat it here?

Objective To research the effects of β-adrenoceptor agonists, isoproterenol and epinephrine, on electrocardiogram and myocardial mechanics in rats with bupivacaine poisoning. Methods Forty-two adult male SD rats were randomly divided into two parts. Each part was then divided into three groups: bupivacaine+saline group (group BS), bupivacaine+isoproterenol group (group BI) and bupivacaine+epinephrine group (group BE), 7 rats in each group. The rats were anesthetized intraperitoneal with 10% chloral hydrate. After bupivacaine was intravenously infused at 0.75 mg·kg-1·min-1 for 12 minutes and 40 seconds, 0.4 ml of normal saline, or isoproterenol (0.08 mg/kg), or epinephrine (6 μg/kg or 3 μg/kg) was caudal intravenously injected. In part one, electrocardiogram was continually monitored to analyze and record the duration of PR, QRS and heart rate. In part two, ventricular pressure waveform was monitored and left ventricular hemodynamic variables were continually recorded. Results Prolonged PR interval, widened QRS interval and decreased heart rate were observed in myocardium intoxicated by bupivacaine (all P<0.05). The effects of isoproterenol and epinephrine on PR interval and QRS interval in myocardium intoxicated by bupivacaine could not be observed markedly. When isoproterenol and epinephrine were injected intravenously respectively for 1 minute, the heart rate increased rapidly in the two groups (all P<0.05). However, there was no difference of the monitoring point after 1 minute. Bupivacaine could reduce left ventricular systolic pressure (LVSP), increase left ventricular end-diastolic pressure (LVEDP), decrease maximum rate of left ventricular pressure rise (+dp/dt max) and maximum rate of decrease of left ventricular internal pressure (-dp/dt max), and the results were statistically significant (all P<0.05) . Isoproterenol and epinephrine could aggravate the inhibitory effect of bupivacaine on myocardial, as a result of reduced LVSP and +dp/dt max. The inhibitory effects in the other two groups were statistically significant at 3 minutes after administration as well as other time points compared with group BS. But there was no significant effect on LVEDP and -dp/dt max. Conclusion Bupivacaine can depress myocardial conduction and left ventricular function in rats. β-adrenoceptor agonists such as isoproterenol and epinephrine can significantly aggravate bupivacaine-induced cardiotoxicity on left ventricular function. β-adrenoceptor agonists have no effect on bupivacaine-induced conductional toxicity in rats. However, they can improve the myocardial autorhythmicity of bupivacaine-induced. Key words: Isoproterenol; Epinephrine; Bupivacaine; Drug toxicity; Myocardium; Electrocardiography

Purpose: To investigate the analgesic effect of alkalized lidocaine on wound dressing operation in burn patients. Methods: 160 burn patients were divided into intervention group (N = 80) and control group (N = 80). The control group was treated with routine burn dressing, and the intervention group was sprayed with a 10: 1 configuration of 2% lidocaine and 5% sodium bicarbonate mixture spray. The heart rate (HR), peripheral oxygen saturation (SpO(2)), and pain (assessed using a visual analog scale [VAS]) were recorded 10 min before, during, and 10 min after debridement and dressing. The simplified version of the McGill pain questionnaire (SF-MPQ) was used to evaluate pain level. Results: The HR in the intervention group was significantly lower than that in control group (P < 0.001). The SpO(2) during the debridement and dressing in the intervention group was significantly higher than that in the control group (P < 0.001). The intervention group showed significantly lower VAS scores than control group (P < 0.001), and the pain sensation scores and pain scores during and after the debridement and dressing in the intervention group were significantly lower than those in the control group (P < 0.001). Conclusion: Alkalized lidocaine has significant analgesic and sedative effects during debridement and dressing of burn wounds, and it can relieve the anxiety and fear in burn patients, making patients relaxed and more amenable to undergo the debridement treatment.

Objective To investigate the effect and mechanism of isoprenaline,a β1-adrenergic receptor agonist,on mitochondrial edema of cardiomyocytes induced by bupivacaine.Methods Six healthy pathogen-free male SD rats,weighing 180-220 g,were received enzymatic hydrolysis separation for myocardial cells,which were randomly divided into 4 groups:physiological saline group (control group),bupivacaine group,bupivacaine+ isoprenaline group,and bupivacaine+ isoprenaline +esmolol group.The myocardial cells were electrically stimulated to induce rhythmic contraction for 60 s.Electron microscopy of myocardial mitochondria was performed to assess the damage of the structure.The amount of mitochondrial reactive oxygen species (ROS) was quantitatively measured by ROS assay kit in the above cardiomyocytes.(Repeat 3 times and take the average).Results The mitochondrial edema score and ROS production was significantly higher in bupivacaine group than those in control group (4 719.95 vs.3 921.94) (all P＜0.05).The extent of myocardial mitochondrial edema and ROS production were significantly higher in bupivacaine +isoprenaline group than those in bupivacaine group (5 192.25 vs.4 719.95) (all P＜0.05).The mitochondrial edema score and ROS production was significantly lower in bupivacaine + isoprenaline + esmolol group than those in bupivacaine + isoprenaline group (4 709.68 vs.5 192.25) (all P＜0.05).Conclusion The excitation of β31-adrenergic receptor induced by isoprenaline can interfere with mitochondrial metabolism and aggravate mitochondrial edema of cardiomyocytes caused by bupivacaine.