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.

Downregulation of Egr-1 Expression Level via GluN2B Underlies the Antidepressant Effects of Ketamine in a Chronic Unpredictable Stress Animal Model of Depression.

Ketamine is a non-competitive antagonist of N-methyl-D-aspartate receptors (NMDARs). Growing evidence suggests that a single dose of ketamine produces a series of rapid and remarkable antidepressant properties. However, the mechanisms remain unclear. In our study, the antidepressant properties of a single dose of ketamine (10 mg/kg, i.p.) in mice exposed to chronic unpredictable stress (CUS) were assessed using the open-field test (OFT) and the forced swimming test (FST). Early growth response 1 (Egr-1) and postsynaptic density protein 95 (PSD-95) mRNA and protein expression levels were examined using qRT-PCR and western blot, respectively. Dendritic spine density in the CA1 region of the hippocampus was detected by Golgi staining. AMPAR currents in hippocampal slices were measured by electrophysiology. Our study showed that CUS induced a significant depression-like behavior accompanied by an upregulation of Egr-1 and downregulations of PSD-95, spine density, and AMPAR currents in the hippocampus, and a single dose of ketamine rapidly restored these changes. Interestingly, a single dose of Ro-25-6981 (an GluN2B antagonist, 10 mg/kg, i.p.) or Egr-1 siRNA, but not NVP AAM077 (an GluN2A antagonist, 10 mg/kg, i.p.), could produce the same antidepressant effects as ketamine. These data demonstrate that ketamine may produce its rapid antidepressant effects by downregulating the expression of Egr-1 via blocking GluN2B in the hippocampus.

Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom.

BACKGROUND: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. OBJECTIVE: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. RESULTS: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. LIMITATIONS: Limitations include the fact that there was demyelination of the cervical cord (C8-T1) in the control group because of inappropriate manipulation. CONCLUSION: Repeated EA contributes significant analgesic effects in the treatment of BPN.

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.

Trigeminal neuralgia induced by cobra venom in the rat leads to deficits in abilities of spatial learning and memory.

BACKGROUND: Patients with chronic pain usually suffer from cognitive impairment, with memory deterioration being the most common deficit that affects daily functioning and quality of life. The causes for this impairment are not clear despite intensive clinical studies. Few studies have evaluated impaired learning using animal models of persistent pain. OBJECTIVE: In this study, a new trigeminal neuralgia model induced by cobra venom was adopted to explore effects of chronic pain on spatial learning and memory in rats. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Thirty adult male Sprague-Dawley rats were randomly divided into 2 groups (n = 15): NS control group and cobra venom group, 0.9% sterile saline or cobra venom solution was injected into the sheath of the infraorbital nerve (ION), respectively. The development of trigeminal neuralgia was accessed by changes in free behavioral activity 3 days before the surgery and 3, 7, 12, 20, and 30 days after the surgery to identify whether the model was successful or not. Morris water maze test determined the abilities of spatial learning and memory at the time points before the surgery, and 2 weeks and 5 weeks after the surgery. We also observed the ultrastructure of the ION and medulla oblongata of rats following 8 weeks of chronic trigeminal neuropathic pain. RESULTS: Rats with the cobra venom injection displayed significantly more face grooming and fewer exploratory activities compared to the NS control group or baseline (P < 0.01). Both groups improved their latency to reach the platform with the largest difference on the first day (P < 0.01), but without memory deficits in a probe trial for the second water maze protocol. For the third water maze testing, the rats in the cobra venom group experienced decreased abilities of spatial learning and memory, a longer latency with spatial memory deficits during the probe trial (P < 0.05). At the ultrastructural level, we found changes in the medulla oblongata after cobra venom injection resulting in severe demyelination and loss of axons that might be implicated in the causes of cognitive deficits. LIMITATIONS: Limitations include partial vision loss in the eye on the lesion side of the rats that might be missed and the absence of evaluating the ultrastructural changes in other parts of the brain. CONCLUSIONS: The results of this study suggest that trigeminal neuralgia induced by cobra venom in adult rats can impair spatial learning and memory function over time and results in demonstrable changes in the ultrastructure of the medulla oblongata. This new animal model may be useful for future studies on the effect of chronic pain on learning and cognition.