Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats.

Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery. Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed. Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3­kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1ß in the hippocampus (P<0.05). Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review.

The authors present the clinical case of a 67-year-old man with severe insomnia for 5 years with an exacerbation about 1 year before consultation. He did not have enough concentration and energy for his daily work and developed depression and anxiety because of his excessive daytime sleepiness. During his insomniac state, a drug treatment provided partial relief, but the effects were not long-lasting. Consequently, the drug dosage increased, and major side effects gradually manifested. We decided to use a completely new therapeutic strategy for this patient to improve his sleep quality and mental symptoms. In time, the patient could stop oral medications and that is multimodal sleep. After the end of multimodal sleep, the patient typically experiences improvement in sleep quality and architecture. Additionally, the dosage of hypnotics used before multimodal sleep is discontinued without severe withdrawal symptoms. CITATION: Zhang J-F, Williams JP, Zhao Q-N, et al. Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review. J Clin Sleep Med. 2021;17(8):1737-1742.

Feasibility of Patient-Controlled Sleep with Dexmedetomidine in Treating Chronic Intractable Insomnia.

BACKGROUND: Patient-controlled analgesia (PCA) is an "on-demand" system which allows patients to self-administer intravenous medications in small bolus doses. Based on the principles of PCA, we developed Patient-Controlled Sleep (PCSL) for chronic intractable insomnia where the traditional analgesics in PCA were replaced with dexmedetomidine (Dex), an alpha-2 agonist widely used for premedication, sedation, anxiolysis and analgesia. The purpose of this study was to assess the feasibility of the new method for the treatment of chronic intractable insomnia. PATIENTS AND METHODS: Patients with chronic intractable insomnia undergoing PCSL (n=20) were evaluated with the Pittsburgh Sleep Quality Index (PSQI), Symptom Checklist 90 (SCL-90), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) before and after the treatment. The patient characteristics, overall outcomes and related side effects were also assessed. RESULTS: Fifteen patients completed the treatment protocol. The duration of PCSL varied from a few days to four months, and the dosage of Dex gradually decreased without eliciting signs or symptoms of tolerance or physical dependence. The sleep quality improvement occurred immediately after the therapy in 12/15 patients, and of which, 7/12 patients achieved continuously improved sleep quality in follow-up. CONCLUSION: PCSL with Dex might be a potential treatment for patients with chronic intractable insomnia. However, it is an off-label use, and the potential side effects of dexmedetomidine with long-term use needs further evaluation.

Pain management after ambulatory surgery: a prospective, multicenter, randomized, double-blinded parallel controlled trial comparing nalbuphine and tramadol.

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus.

BACKGROUND: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. OBJECTIVES: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. STUDY DESIGN: This study used an experimental design in rats. SETTING: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). RESULTS: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. LIMITATIONS: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions. KEY WORDS: Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.

Use of propofol for prevention of post-delivery nausea during cesarean section: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Nausea and vomiting are common, undesirable symptoms during cesarean section. We conducted this study to assess the antiemetic properties of propofol for the prevention and immediate treatment of post-delivery nausea and vomiting during cesarean section under combined spinal-epidural anesthesia. METHODS: Eighty women undergoing elective cesarean delivery under combined spinal-epidural anesthesia were randomized to receive either propofol at a plasma concentration of 1000 ng/mL or normal saline immediately after clamping of the umbilical cord. The incidence of post-delivery nausea and vomiting, patients requiring rescue antiemetic, bispectral index, sedation score, and the incidence of hypotension were assessed intraoperatively. Satisfaction and neonatal behavioral neurological assessments were evaluated postoperatively. RESULTS: The incidence of nausea was significantly lower in the propofol group compared to the placebo group (25% versus 60%, P < 0.001). The incidence of retching and vomiting showed no significant difference between the two groups. Propofol 20 mg as a rescue antiemetic was significantly effective in both the groups. Satisfaction level of patients and obstetricians in the propofol group was higher than in the placebo group. There was no statistical difference in the incidence of hypotension between the two groups both pre- and post-delivery. There was no difference in postoperative neonatal behavioral neurological assessment between groups. CONCLUSION: Propofol at a plasma concentration of 1000 ng/mL significantly reduced the incidence of post-delivery nausea compared to placebo, but had no effect on reducing retching or vomiting episodes during cesarean section.

Electroconvulsive Therapy Under General Anesthesia With Cisatracurium, Laryngeal Mask Airways, and Bispectral Index.

OBJECTIVES: Electroconvulsive therapy (ECT) has dramatically reduced musculoskeletal complications when carried out with muscle relaxants under general anesthesia. However, seizure quality can be affected by the depth of anesthesia and choice of anesthetic agent. The purpose of this study was to describe a general anesthetic technique for ECT by using laryngeal mask, bispectral index (BIS), and muscle relaxant monitoring. METHODS: Twenty-one patients, between ages 18 and 70 years (American Society of Anesthesiologists physical status I-III), who underwent a total of 89 sessions of ECT were examined in a retrospective study. Anesthesia was induced by use of propofol (1.0 mg/kg) followed by cisatracurium (0.2 mg/kg). The BIS, train-of-four, and end-tidal carbon dioxide were all monitored continuously. A laryngeal mask airway was used to maintain and protect the airway during the procedure. Electroconvulsive therapy stimuli were applied bilaterally when the train-of-four was assessed as being zero and BIS scores were 70. All patients then received 5 µg sufentanil and 2 mg midazolam, while titrated to maintain the BIS value at 40 to 50, before the muscle relaxation exhibited complete recovery. RESULTS: The mean duration of treatment process takes approximately 82.5 minutes. Mean (SD) seizure length was 58.8 (28.3) seconds, with 4.5% incidence of restimulation per treatment. Incidence of awareness was 0%. No patients exhibited delirium, nausea, vomiting, or myalgia in the postseizure phase. CONCLUSIONS: Bispectral index monitoring of the depth of anesthesia may have improved seizure quality, and awareness did not occur.

Rat Model of Trigeminal Neuralgia Using Cobra Venom Mimics the Electron Microscopy, Behavioral, and Anticonvulsant Drug Responses Seen in Patients.

BACKGROUND: A new animal model of trigeminal neuralgia produced by injecting cobra venom into the infraorbital nerve (ION) trunk in rats had been developed. We tested and extended the model by observing the ultrastructural alterations of neurons and ameliorative effect of pregabalin in cobra venom-induced pain behaviors of rats. OBJECTIVES: The goal of this study was to prove the feasibility of the cobra venom-induced model of trigeminal neuralgia and to demonstrate the demyelination change of ION and medulla oblongata is the major pathological change of trigeminal neuralgia. STUDY DESIGN: An experimental study. SETTING: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Experiments were carried out on male Sprague-Dawley rats. Video recordings were taken after the cobra venom injection and pregabalin administration. Ultrastructural alterations of ION and medulla oblongata were observed at the electron microscopic level. We also observed alteration in pain behaviors by analysis of video recordings. RESULTS: Compared to the preoperative and sham-operated group rats, experimental group rats exhibited significant changes in exploratory, resting, face-grooming, and head-shake behaviors on 3, 7, 14 days after operation (P < 0.01). The demyelination changes of ION and medulla oblongata were evident after administration of cobra venom to the ION. Compared to the pre-treated (no pregabalin administration) and control group rats, pregabalin group rats showed profound changes in exploratory, resting, face-grooming, and head-shake behaviors throughout the 14 day study period after treatment with drugs (P < 0.01). LIMITATIONS: Ultrastructural alterations of ION and medulla oblongata were not examined after the treatment with pregabalin. CONCLUSIONS: Video recordings of free behaviors and pregabalin application prove the feasibility of the rat model of trigeminal neuralgia. The results of electron micrographs are consistent with a previous study in humans showing that the demyelination change of axons is the major pathological change of trigeminal neuralgia. The central demyelination alterations may explain why the mechanical threshold was found to be decreased on the non-operated side of experimental animals.

Spine surgery may cause more spinal epidural hematomas than spinal puncture.

BACKGROUND: Spinal epidural hematoma (SEH) is a rare but acute and possibly devastating clinical event. The purpose of this study is to assess the multiple etiologies of SEH seen in an academic medical center over a 15-year span. We have examined the etiologies of SEH occurring in a single institution, the University of Pittsburgh Medical Center (UPMC) over the last fifteen years using an electronic record keeping system and database: the Medical Archive Retrieval System (MARS). METHODS: We screened MARS from 1986 - 2001 using key words: epidural, hematoma and spinal. All potential SEH cases were reviewed and only those confirmed by surgical intervention were identified as positive SEH and reported in this study. RESULTS: There were 17 cases of confirmed SEH. Among them, seven cases were from spontaneous bleeding, seven cases following spinal surgery, and three cases from traumatic spinal fracture. There were no findings of SEH that were related to spinal or epidural anesthesia. Among the seven patients with spontaneous SEH; two were receiving anti-coagulants for deep venous thrombosis (DVT) and had elevated prothrombin time (PT) and activated partial thromboplastine time (APTT), one had hemophilia (type B), four had hypertension, and three out of seven had chronic renal or liver disease. Among postoperative SEH patients, two of the seven patients were receiving chemotherapy and radiation therapy and one had ongoing hemodialysis for renal failure. Among three patients with traumatic SEH, two had ankylosing spondylitis. Six patients had a history of alcohol abuse. CONCLUSIONS: Spontaneous bleeding is by far the leading cause of SEH with spinal surgery being the second leading cause. Patients with multiple co-morbidities that result in coagulopathy from a variety of causes include liver or renal disease, alcohol abuse, radiation therapy, or chemotherapy. Neuraxial anesthesia is an extremely rare cause of SEH.