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).

Combined high-voltage pulsed radiofrequency and ozone therapy versus ozone therapy alone in treating postherpetic neuralgia: a retrospective comparison.

Postherpetic neuralgia (PHN) is a devastating disease with extraordinarily poor treatment outcomes. Both pulsed radiofrequency (PRF) and ozone have good effects on the treatment of the disease. However, whether PRF and ozone have a synergistic effect on PHN remains unclear. Therefore, this study aimed to assess the therapeutic effects of ozone alone and in combination with PRF in the treatment of PHN. Ninety-one patients with PHN were assigned into two groups: PRF combined with ozone (PRF + ozone group, n = 44) and ozone therapy alone (ozone group, n = 47). In PRF + ozone group, the high-voltage, long-duration PRF was applied to the target dorsal root ganglions. Then ozonated water (11.5 µg/mL) was injected through the inner cannula. In the ozone group, all other processes were the same as those in the PRF + ozone group apart from the electrical stimulation. The therapeutic efficacy was evaluated by visual analog scale and tactile sensation at pre-treatment and post-treatment 3, 6, and 12 months. Compared with pre-treatment data, the visual analog scale score was significantly decreased in both groups after treatment. Compared with the ozone group, the visual analog scale score was significantly decreased in the PRF + ozone group at 3, 6, and 12 months. Similarly, the tactile sensation was also significantly decreased at post-treatment when compared to pre-treatment. However, there were no statistical differences between the two groups. Regression analysis results showed that the history of diabetes mellitus and age had significant negative and positive effects, respectively, on the treatment results. To conclude, the administration of PRF + ozone and ozone therapy alone could both improve pain symptoms. Moreover, treatment effects and total efficacy rates tended to be higher for the combination of PRF and ozone than ozone alone. This conclusion was especially true for long-term therapeutic effects.

Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00450-8.

Intraperitoneal ozone injection prevents REM sleep deprivation - induced spatial learning and memory deficits by suppressing the expression of Sema3A in the hippocampus in rats.

Objectives: Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting. Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Electroacupuncture Alleviates Thalamic Pain in Rats by Suppressing ADCY1 Protein Upregulation.

BACKGROUND: Thalamic pain (TP), also known as central post-stroke pain, is a chronic neuropathic pain syndrome that follows a stroke and is a severe pain that is usually intractable. No universally applicable and effective therapies have been proposed. Emerging studies have reported that electroacupuncture (EA) can potentially be used as an effective therapy for the treatment of neuropathic pain. However, whether EA influences TP and if so, by what potential mechanism, remains poorly understood. OBJECTIVE: The aim of this study was to detect the efficacy of EA and explore possible mechanisms for treating TP. STUDY DESIGN: Controlled animal study. SETTING: The laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague Dawley rats were randomly divided into 3 groups (n = 15 / group): sham-operated (SH) group, thalamic pain model (TP) group, EA treatment (EA) group. After the TP rat model was successfully established, EA was used for intervention. During the experiment, the mechanical pain thresholds of rats were detected among the groups. The right thalamus of the rats was extracted on postoperative day 28 for RNA-sequencing (RNA-Seq) analysis to find the changes in gene expression in different groups of rats. The key genes were screened using reverse transcription-polymerase chain reaction (RT-PCR) detection and subsequently identified with western blotting and immunofluorescence. RESULTS: The mechanical withdrawal threshold (MWT) value of the right facial skin in the TP group and the EA group decreased significantly on the 3rd day after surgery, compared to the SH group (P < 0.01). From 7 to 28 days, the MWT value increased continually in the EA group; however, there was no significant change in the TP group. The results of RNA-seq showed that compared to the TP group, 377 genes changed in the EA group. Moreover, ADCY1 expression increased significantly in the TP group as compared to the SH group, while EA treatment reversed the expression of ADCY1. LIMITATIONS: In addition to ADCY1, the mechanism(s) of other signaling pathways in TP need to be explored in future research. CONCLUSIONS: EA treatment may promote the recovery of TP model rat by regulating ADCY1 expression.

A solid-supported organocatalyst for asymmetric Mannich reaction to construct C2-quaternary indolin-3-ones.

A simple and novel solid-supported organocatalyst from a 2-chlorotrityl chloride resin-immobilized 4-hydroxyproline was developed, and this organocatalyst has been used for the asymmetric Mannich reaction of 2-aryl-3H-indol-3-ones and aldehydes/ketones. A series of C2-quaternary indolin-3-ones were prepared in good yields (up to 83%) and with excellent diastereoselectivities (up to 20 : 1) and enantioselectivities (up to 99% ee). In addition, the organocatalyst can be recovered by simple filtration and also be reused for the asymmetric Mannich reaction without significant loss of catalytic efficiency.

Potential Molecular Mechanisms of Electroacupuncture With Spatial Learning and Memory Impairment Induced by Chronic Pain on a Rat Model.

BACKGROUND: It is frequently reported that neuropathic pain is associated with abnormalities in brain function and structure as well as cognitive deficits. However, the contributing mechanisms have remained elusive. OBJECTIVES: We aimed to investigate the systemic ultrastructural changes of the peripheral nervous system (PNS) and central nervous system (CNS) in rats with trigeminal neuralgia (TN) induced by cobra venom, as well as the effects and mechanisms of electroacupuncture (EA) and pregabalin (PGB) on TN. 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 randomly divided into 4 groups (n = 12/group): cobra venom (CV), PGB, EA, and sham-operated (SHAM). The development of pain-related behaviors and spatial learning and memory abilities were measured using video recordings and Morris water maze tests, respectively. The ultrastructural changes of the PNS and CNS were examined using transmission electron microscopy. We also screened the differentially expressed genes and proteins in the prefrontal cortex  and hippocampus using  ribonucleic acid sequencing and isobaric tag for relative and absolute quantitation techniques, respectively. Data for the behavioral tests and molecular biology were analyzed with a one-way analysis of variance. RESULTS: The rats in the CV group exhibited long-lasting pain-like behaviors, cognitive deficits, and systemic ultrastructural changes. Both EA and PGB alleviated the chronic pain syndrome, but EA also inhibited the chronic pain-induced cognitive dysfunction and restored normal cellular structures, while PGB was associated with no improvements. Transcriptomic and proteomic analyses revealed marcks, pak2 and acat1 were altered in rats with TN but were adjusted back to baseline by EA but not by PGB. LIMITATIONS: We examined systemic ultrastructural alterations at different levels of the nervous system; however, the detailed timeline of the damage process was not explicitly delineated.  Moreover, the current study provides only preliminary evidence for the neurobiological mechanisms of cognitive impairment resulting from chronic pain.  Further research is still necessary (using models such as gene knockout rats and cell cultures) before a detailed mechanism can be postulated. CONCLUSIONS: EA treatment may offer significant advantages when compared to PGB for the treatment of cognitive impairment associated with chronic pain. Moreover, marcks, pak2 and acat1 may be the potential therapeutic targets of EA.

Development of a single-step fluorogenic sirtuin assay and its applications for high-throughput screening.

Sirtuins (SIRTs) are a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases. Since SIRTs have different subcellular locations and different preferences for deacylation activity, SIRTs are not only highly gaining significance in biological functions but also implications in human diseases. Therefore, it is valuable to establish a high-throughput screening method for the rapid and accurate discovery of SIRT modulators. In this study, we designed and synthesized small molecules 4a-d as fluorogenic probes based on the different lysine substrates of SIRTs, which can be recognized and catalyzed by SIRTs and then spontaneous intramolecular transesterification can give the fluorescence. We have undertaken a comprehensive study of these fluorogenic probes with different SIRTs for assay optimization, validation, kinetics, parameters, and applications of high-throughput screening formats. We envision that these probes will provide useful and powerful tools for the highly efficient discovery of more SIRT inhibitors.

Treatment of Femoral Head Osteonecrosis with Ozone Therapy: Pilot Trial of a New Therapeutic Approach.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive and painful disorder due to impaired blood supply to the femoral head, yet little is known about the effect of ozone therapy in femoral head necrosis. OBJECTIVES: We aimed to evaluate the clinical and radiographic outcomes of ozone therapy in the treatment of ONFH. STUDY DESIGN: Nonrandomized clinical trial. SETTINGS: The study was conducted in a single-center, academic institution. METHODS: A total of 71 patients (107 hip joints) with Association Research Circulation Osseous (ARCO) stage-I, II, III, and IV ONFH were included and assigned to undergo either intraarticular O2-O3 mixture hip injections with ozonated autohemotherapy (ozone therapy group, n = 39, 58 hip joints) or protected weight bearing (control group, n = 32, 49 hip joints). The primary outcomes included the Visual Analog Scale (VAS) for pain intensity and Harris Hip Score (HHS) for hip function. The secondary outcomes included bone marrow edema examination, and conversion to total hip arthroplasty (THA). RESULTS: Ozone therapy effectively improves VAS for pain intensity and HHS during the follow-up period compared to the control group. Ozone therapy showed a significant resolution of bone marrow edema of the femoral head compared to the control group (P < 0.001). Thirteen of the 49 hips (26.53%) in the control group underwent THA, whereas only 6 hips (10.34%) in the ozone therapy group required THA during a 30-month follow-up (P = 0.041). The cumulative analysis revealed a low rate of conversion to THA in the ozone therapy group (logrank test; P = 0.022). LIMITATIONS: The study is limited by a single treatment protocol in addition to the lack of a randomized design. CONCLUSIONS: Ozone therapy was associated with significant pain relief, improvement in hip function, and bone marrow edema resolution that may delay the need for THA in patients affected by ONFH.Institutional Review Board (IRB) approval number: HK2018-10-28.Clinical trials registration number: ChiCTR1900023449.

Neuropathic Pain Creates Systemic Ultrastructural Changes in the Nervous System Corrected by Electroacupuncture but Not by Pregabalin.

PURPOSE: It is unclear whether neuropathological structural changes in the peripheral nervous system and central nervous system can occur in the spared nerve injury model. In this study, we investigated the pathological changes in the nervous system in a model of neuropathic pain as well as the effects of electroacupuncture (EA) and pregabalin (PGB) administration as regards pain relief and tissue repair. PATIENTS AND METHODS: Forty adult male SD rats were equally and randomly divided into 4 groups: spared nerve injury group (SNI, n = 10), SNI with electroacupuncture group (EA, n = 10), SNI with pregabalin group (PGB, n =10) and sham-operated group (Sham, n=10). EA and PGB were given from postoperative day (POD) 14 to 36. EA (2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-1.5-2 mA) was applied to the left "zusanli" (ST36) and "Yanglingquan" (GB34) acupoints for 30 minutes. The mechanical withdrawal thresholds (MWTs) were tested with von Frey filaments. Moreover, the organizational and structural alterations of the bilateral prefrontal cortex, hippocampus, sciatic nerves and the thoracic, lumbar spinal cords and dorsal root ganglions (DRGs) were examined via light and electron microscopy. RESULTS: MWTs of left hind paw demonstrated a remarkable decrease in the SNI model (P < 0.05). In the SNI model, ultrastructural changes including demyelination and damaged neurons were observed at all levels of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, EA improved MWTs and restored the normal structure of neurons. However, the effect was not found in the PGB treatment group. CONCLUSION: Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA and PGB can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while PGB is associated with no improvement.

Preprocedure ultrasound imaging combined with palpation technique in epidural labor analgesia.

BACKGROUND: For parturients with paroxysmal uterine contraction pain, rapid analgesia is needed. We used preprocedure ultrasound imaging combined with the palpation technique in epidural analgesia for labor, and evaluated the usefulness of this technique in epidural labor analgesia. AIM: To evaluate the usefulness of preprocedure ultrasound imaging in epidural analgesia for labor. METHODS: In this prospective randomized observational study, 72 parturients were assigned to two groups (combined or palpation group). The target interspace of all parturients was first identified by the palpation technique. Then in the combined group, preprocedure ultrasound imaging was used before epidural puncture. In the palpation group, only the traditional anatomical landmarks technique (palpation technique) was performed. The primary outcome was total duration of the epidural procedure (for the ultrasound group, the duration of the preprocedure ultrasound imaging was included). The secondary outcomes were the number of skin punctures, the success rate at first needle pass, the number of needle passes, the depth from the skin to epidural space, and the complications of the procedure. RESULTS: Total duration of the epidural procedure was similar between the two groups (406.5 ± 92.15 s in the combined group and 380.03 ± 128.2 s in the palpation group; P = 0.318). A significant improvement was demonstrated for epidural puncture and catheterization in the combined group. The number of needle passes was 1.14 in the combined group and 1.72 in the palpation group (P = 0.001). The number of skin puncture sites was 1.20 in the combined group and 1.25 in the palpation group (P = 0.398). The success rate at first needle pass was 88.89% in the combined group and 66.67% in the palpation group (P = 0.045). CONCLUSION: This study demonstrated that the total duration of epidural procedures with preprocedure ultrasound imaging combined with the palpation technique was not longer than the traditional anatomical landmarks technique, which were performed by six experienced anesthesiologists in parturients with normal weights undergoing labor analgesia.

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.

A multicenter survey of perioperative anxiety in China: Pre- and postoperative associations.

OBJECTIVES: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting. METHODS: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2. RESULTS: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant. CONCLUSION: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively.

Feasibility of Ultrasound-Guided Peritoneal Perfusion with Ozone in the Treatment of Chronic Pelvic Pain: A Bicenter Retrospective Analysis.

BACKGROUND: Numerous therapies have been developed for the treatment of chronic pelvic pain (CPP). Oxygen-ozone therapy is a new method for the treatment of CPP. OBJECTIVES: This article evaluated the feasibility of ultrasound-guided peritoneal perfusion with ozone in patients with CPP. STUDY DESIGN: This is a bicenter retrospective study. SETTING: The study was conducted at 2 pain centers of a university hospital. METHODS: The medical records of patients with CPP (n = 60) from March 2016 until October 2018 were collected and reviewed. Group A contained 19 patients who were treated with a 1500 mcg dose of ozonated water (10 mcg/mL concentration and 150 mL volume), group B contained 23 patients using the same dose of ozonated water but a 15 mcg/mL concentration and 100 mL volume. Group C included 18 patients using a similar ozone dose but delivered in an oxygen-ozone mixture (15 mcg/mL concentration and 100 mL volume oxygen-ozone mixture). Visual Analog Scale (VAS) scores for pain of the 3 groups were compared at pretreatment, posttreatment, 1, 3, and 6 months posttreatment. The injection pain was evaluated using a 4-point verbal rating scale. Quality of life (QoL), anxiety, and depression were assessed at pretreatment and at 6 months posttreatment. RESULTS: The VAS scores of the 3 groups decreased over time following treatment. Group A showed much higher pain scores compared with groups B and C at 1, 3, and 6 months posttreatment. However, the injection pain for groups B and C was higher than group A, but there was no difference seen between group B and C. At 6 months posttreatment, the QoL for all patients improved compared with pretreatment, whereas the anxiety and depression did not demonstrate differences. LIMITATIONS: The main limitations of this study are the retrospective study design, limited case number, and short follow-up period. CONCLUSIONS: Ultrasound-guided peritoneal perfusion with ozone is a feasible therapy for patients with CPP.

Dexmedetomidine Reverses Postoperative Spatial Memory Deficit by Targeting Surf1 and Cytochrome c.

Anesthesia and surgery are associated with perioperative neurocognitive disorders (PND). Dexmedetomidine is known to improve PND in rats; however, little is known about the mechanisms. Male Sprague-Dawley rats were subjected to resection of the hepatic apex under propofol anesthesia to clinically mimic human abdominal surgery. The rats were divided into four groups: control group (C), anesthesia group (A), model group (M), and model + dex group (D). Cognitive function was evaluated with the Morris water maze (MWM). Neuronal morphology was observed with H&E staining, Nissl's staining and immunohistochemistry. Transcriptome analysis and quantitative real-time PCR were performed to investigate functional mitochondrial mRNA changes in the hippocampus. Protein levels were measured by Western blotting at 1, 3, and 7 days after surgery. Surgery-induced cognitive decline lasted for three days, but not seven days after surgery in the M group; however, rats in the D group were significantly improved by dexmedetomidine. No significant differences in the number of neurons were observed between the groups after surgery. Rats from the M group showed significantly greater expression levels of Iba-1 and GFAP compared with the C group and the D group. Rats in the M group demonstrated increased Surf1 and Cytochrome c expression on days 1 and 3, but not day 7; similar changes were not induced in rats in the D group. Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, and downregulate the expression of Surf1 and Cytochrome c protein in the hippocampus of rats in a PND model.

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.

Efficacy and Safety of Percutaneous Ozone Injection Around Gasserian Ganglion for the Treatment of Trigeminal Neuralgia: A Multicenter Retrospective Study.

BACKGROUND: Ozone injection around Gasserian ganglion (OIAGG) has been reported to be an effective treatment for trigeminal neuralgia (TN); however, there remain areas for improvement. To overcome one of these limitations, a multicenter examination of application would be extremely helpful. OBJECTIVE: The goal of this report was to assess the efficacy of OIAGG for refractory TN across multiple centers and to explore factors predictive of successful treatment. DESIGN: A multicenter, retrospective study. SETTING: The study was conducted across 3 pain centers across China. PATIENTS AND METHODS: A total of 103 subjects from 3 pain centers were enrolled in the study. An ozone-oxygen mixture gas at a concentration of 30 µg/mL was injected into the area around the Gasserian ganglion performed under C-arm X-ray guidance. Primary outcome measures included a pain assessment using a visual analog scale (VAS) and the Barrow Neurological Institute (BNI) pain intensity scale. Clinical assessment of patients for these outcome measures was performed at pretreatment, post-treatment, 6 months, 1 year and 2 years after the OIAGG. RESULTS: Successful pain relief was defined as a score within BNI grades I-IIIa. The pain relief rates at post-treatment, 6 months, 1 year and 2 years after the procedure were 88.35%, 86.87%, 84.46% and 83.30%, respectively. The VAS at each observation time point was significantly different from the preoperative levels (P<0.05). Logistic regression analysis showed that previous nerve damage had a significant effect on the treatment results. No significant complications or side effects were found during or after treatment. CONCLUSION: This multicenter research confirms our previous single center results that OIAGG is both effective and safe for patients with TN.

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.

Ozone Inhibits APP/Aß Production and Improves Cognition in an APP/PS1 Transgenic Mouse Model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder without effective treatment. Accumulating evidence demonstrates the production and deposition of amyloid-ß peptides (Aß) in the pathological mechanism of this disease. In our study, we investigated the effect of an ozone intraperitoneal injection on AD pathology in APP/PS1 transgenic mouse model. The male mice (5-months-old) received either ozone intraperitoneal injection (at 30 µg/ml or 50 µg/ml) or abdominocentesis administration daily for 25 days, and they were evaluated in the Morris water maze and the open field test for improvements in spatial learning-memory and working memory and anxious. Prefrontal cortex and hippocampus amyloid-ß precursor protein (APP), along with other relevant biomarkers for AD, were measured through ELISA, western blot and immunohistochemistry. Results showed that ozone ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic mice, and reduced the level of APP, which supports the therapeutic potential of administration of ozone in APP/PS1 mice.

The effect of ultrasound-guided percutaneous ozone injection around cervical dorsal root ganglion in zoster-associated pain: a retrospective study.

OBJECTIVE: This study was to evaluate the effectiveness of ultrasound-guided percutaneous ozone injections around the cervical dorsal root ganglions of zoster-associated pain (ZAP) patients. STUDY DESIGN: Retrospective comparative study. SETTINGS: The study was conducted at a pain center of a university hospital. PATIENTS AND METHODS: From June 2016 to July 2017, a total number of 30 patients with ZAP were treated with ultrasound-guided percutaneous ozone injection around the cervical dorsal root ganglion (DRG) at the injured nerve level (C2-C8). A volume of 3 mL ozone-oxygen mixture at a concentration of 30 µg/mL was injected into the area around the DRG. Patients were divided into two groups according to their disease duration: group A (at or <3 months) and group B (>3 months). The pain severity was assessed according to a visual analog scale, and imaging changes were evaluated by ultrasound. Patient improvements in pain and neurologic function were evaluated during a follow-up period from 1 to 3 months. RESULTS: The data showed that ozone injections reduced pain in patients with ZAP. However, the success rate of group A was higher than group B. After the injection, the von Frey data demonstrated decreases in both groups, but, there were no significant differences between the groups. Moreover, univariate logistic regression analysis and multivariate regression analysis showed a history of diabetes mellitus had a significant effect on the treatment results. CONCLUSIONS: Percutaneous ozone injection around the DRG might be a useful method for treatment-resistant cases of ZAP at the cervical level. Institutional Review Board (IRB) approval number: HK2017-1130.