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Lei Gao,1,2,&ast; Jian-Feng Zhang,3,&ast; John P Williams,4 Yi-Ning Yan,1 Xi-Lai Xiao,1 Wan-Rui Shi,5 Xiao-Yan Qian,1 Jian-Xiong An1– 3,6 1Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2School of Anesthesiology, Weifang Medical University, Weifang, Shangdong, People’s Republic of China; 3Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 6School of Medical Science & Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University, Beiyuan Road 3#, Beijing, 100012, People’s Republic of ChinaTel +86 13801281750Fax +86 59520233Email anjianxiong@yeah.netPurpose: 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.Keywords: neuropathic pain, structural changes, electroacupuncture, pregabalin

Jian-Xiong An,1– 3 John P Williams,4 Qi-Wu Fang,1 Yong Wang,1 Hui Liu,1 Le Shi,5 Wen-Hao Zhang1,2 1Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3School of Medical Science & Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, People’s Republic of China; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Key Laboratory of Mental Health, Peking University Sixth Hospital, Peking University Institute of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of ChinaCorrespondence: Wen-Hao Zhang Tel +86 159 1096 3901Email zhangwenhao18@mails.ucas.ac.cnBackground: 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.Keywords: insomnia, dexmedetomidine, Patient-Controlled Sleep, biomimetic sleep

Lei Gao,1,2 Ruo-Wen Chen,2 John P Williams,3 Tong Li,4 Wei-Jiang Han,5 Qian-Nan Zhao,2 Yong Wang,2 Jian-Xiong An1,2 1Department of Anesthesiology, Weifang Medical University, Weifang City 261000, Shangdong, People’s Republic of China; 2Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, 100012, People’s Republic of China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; 4Department of Pain, Lanzhou Maternity and Child Healthcare Hospital, Lanzhou, 730030, People’s Republic of China; 5Department of Pain, Xishuangbanna Dai Nationality Autonomous Prefecture People’s Hospital, Xishuangbanna, 666100, People’s Republic of ChinaCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beiyuan Road 3, Beijing 100012, People’s Republic of ChinaTel +86 138 0128 1750Fax +86 10 5952 0393Email anjianxiong@yeah.netBackground: 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.Keywords: trigeminal neuralgia, trigeminal post-herpetic neuralgia, ozone therapy, Gasserian ganglion

Si-Yu Lin,1,2 Shi-Zhong Zhang,1 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Xin-You Gao,2 Yong Wang,2 Wen-Xing Zhao,2 Derek Eastwood,3 Doris K Cope,4 John P Williams4 1China Three Gorges, University School of Medicine, Yichang, China; 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Pain Services, Wirral University Teaching Hospital, Wirral, Merseyside, UK; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 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). 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. Keywords: herpes zoster, neuropathic pain, post-herpetic neuralgia, ozone injection

Jian-Xiong An,1,2 Hui Liu,1 Ruo-Wen Chen,1,2 Yong Wang,1 Wen-Xing Zhao,1 Derek Eastwood,3 John P Williams4 1Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, 2Department of Anesthesiology, Weifang Medical University, Beijing, People’s Republic of China; 3Department of Pain Services, Wirral University Teaching Hospital, Wirral, Merseyside, UK; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The aim of this study was to evaluate the therapeutic effect of computed tomography (CT)-guided percutaneous ozone injection for refractory trigeminal neuralgia. Design: A retrospective evaluation was performed in the study. Setting: The study was conducted at a university hospital pain center. Patients and methods: A total of 29 patients with a clinical diagnosis of refractory trigeminal neuralgia were enrolled. All patients were treated with a percutaneous ozone injection and one patient was excluded. There were 21 patients with classical trigeminal neuralgia (group A) and seven patients with painful trigeminal neuropathy caused by post-herpetic neuralgia (group B). The percutaneous injection was an oxygen–ozone mixture at an ozone concentration of 30 mg/­mL into the Gasserian ganglion performed under CT guidance. The number of ­procedures performed varied from one to as many as 16. Outcomes were evaluated using visual analog scale (VAS) pain scores. Results: The combined VAS scores were 7.11 ± 1.23 pretreatment, 2.86 ± 1.69 posttreatment (P < 0.05) and 3.25 ± 2.01 after 6-month follow-up (P < 0.05). In group A, the VAS scores were 7.10 ± 1.04 pretreatment and 2.90 ± 1.84 posttreatment (P < 0.05). In group B, the VAS scores were 7.14 ± 1.77 pretreatment and 2.71 ± 1.25 posttreatment (P < 0.05). After 6-months follow-up, the VAS score was 3.38 ± 2.18 in group A and 2.86 ± 1.46 in group B, a decrease compared to pretreatment (P < 0.05). VAS of Group A and B showed no difference not only in pretreatment but also in postreatment and follow-up. Conclusion: Percutaneous ozone injection is a safe and effective treatment for patients with refractory trigeminal neuralgia. Keywords: trigeminal neuralgia, percutaneous ozone injection, Gasserian ganglion

Ruo-Wen Chen,1,2 Hui Liu,2 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Yi-De Jiang,2 Doris K Cope,3 John P Williams,3 Rui Zhang,1 Li-Na Sun1 1Department of Anesthesiology, Weifang Medical University, Weifang City, Shandong, 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The objective of this study was to investigate the effects of electro-acupuncture (EA) and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN) in rats. Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. Subjects: Forty adult male Sprague Dawley rats. Methods: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. Results: After treatment, the exploratory behavior increased and the grooming behavior decreased (P0.05). Vacuolar degeneration in the hippocampal neurons was mild in the EA group, while it was severe in the pregabalin group.Conclusion: EA and pregabalin could alleviate TN induced by cobra venom. EA could also inhibit the cognition deficit induced by TN, while pregabalin could not. Keywords: TN, cognition dysfunction, EA, pregabalin, LTP

James P Williams,1 Paul Southern,2 Anya Lissina,3 Helen C Christian,4 Andrew K Sewell,3 Rodney Phillips,1,5,6 Quentin Pankhurst,2 John Frater1,5,6 1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK; 2Davy-Faraday Research Laboratory, Royal Institution of Great Britain, London, UK; 3Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 5James Martin 21st Century School, John Radcliffe Hospital, Oxford, UK; 6Oxford NIHR Biomedical Research Centre, Oxford, UK Abstract: The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. Keywords: nanoparticles, HIV-1, thermotherapy, cytotoxic T-cell

Background and Objectives: We analyzed discharge outcome data after anterior cruciate ligament reconstruction (ACLR) under spinal anesthesia including a perineural femoral catheter and multimodal analgesia/antiemesis. The outcomes specifically addressed in this report are nausea, vomiting, and retching (NVR) and quality of sleep/difficulty falling asleep/daytime restfulness.Methods: ACLR patients were randomized to saline or 0.25% levobupivacaine as a bolus and/or 50-hour infusion. Patients completed the Quality of Recovery 40-item (QoR-40) survey on postoperative days 1 to 4. We analyzed predictors of perfect responses (i.e., no NVR and perfect sleep-restfulness) by pooling these specific QoR-40 items. Prospectively collected QoR-40 data were analyzed retrospectively.Results: Data from 233 participants were analyzed. The addition of the femoral nerve block or perineural catheter did not predict associated improvements in NVR or sleep-restfulness. Previous days' NVR was the most consistent predictor of subsequent NVR, whereas gender and opioid consumption were less consistent predictors. Smoking status was not predictive of NVR. Previous days' sleep-restfulness was a consistent predictor of subsequent sleep-restfulness, whereas the presence of any moderate pain was a less consistent predictor of sleep-restfulness.Conclusions: NVR and quality of sleep-restfulness after the described regional anesthetic with multimodal analgesia and antiemesis is reported. Smoking status was not a predictor of NVR, and gender and opioid consumption were not consistently predictive of NVR. The addition of a femoral nerve block to the described multimodal technique was not associated with NVR or quality of sleep-restfulness. [ABSTRACT FROM AUTHOR]

Background and Objectives: Continuous perineural femoral analgesia has been reported to reduce numeric rating pain scores (NRS, scale 0-10) after anterior cruciate ligament reconstruction (ACLR). In the current study, we determined rebound pain scores in autograft ACLR outpatients after nerve block analgesia resolved.Methods: After standardized spinal anesthesia and perioperative multimodal analgesia, patients received a femoral perineural catheter and 50 hours of saline or levobupivacaine. All patients received levobupivacaine (30 mL of 0.25% as a bolus) before the infusion. Patients completed a pain diary for 6 days, indicating serial NRS scores and perceptions of when nerve block analgesia resolved. Block duration and rebound pain scores were computed.Results: Data from 84 participants' pain diaries were analyzed. Patients receiving saline infusion reported mean nerve block duration of 37 hours versus 59 hours for patients receiving the levobupivacaine infusion (P < .001). Mean rebound pain scores increased by 2.0 (95% confidence interval, 1.6-2.4). Based on the computations used to derive block duration and rebound pain scores, each hour of additional block duration was predictive of a 0.03-unit reduction in rebound pain scores.Conclusions: In an anesthesia care protocol consisting of spinal anesthesia and multimodal analgesia during and after autograft ACL reconstruction, approximately 33 hours of additional nerve block duration were required to reduce rebound pain scores by one unit. Further study is required to determine rebound pain score differences when other local anesthetics and anesthetic/analgesic plans are being used and when other surgeries are being performed. [ABSTRACT FROM AUTHOR]

This study evaluated the effectiveness of a comprehension program integrated with social studies instruction designed for at-risk second graders. The program included instruction in cause-effect text structure, emphasizing clue words, generic questions, graphic organizers, and the close analysis of specially constructed cause-effect target paragraphs. This program was compared (a) to a content-only program that focused only on social studies and did not include text structure instruction and (b) to a no-instruction control. Fifteen classroom teachers, randomly assigned to treatment, provided the instruction. The program improved the comprehension of instructional cause-effect texts, and there were transfer effects on some comprehension measures. The performance of the 2 instructed groups did not differ on any of the content measures, indicating that such integrated instruction can be accomplished without a loss in the amount of content acquired. This study supports our previous findings on the effectiveness of explicit instruction at the primary-grade level. [ABSTRACT FROM AUTHOR]