A New Animal Model of Brachial Plexus Neuralgia Produced by Injection of Cobra Venom into the Lower Trunk in the Rat.

BACKGROUND: To establish a new animal model for the study of neuropathic pain developed by administration of cobra venom to the brachial plexus (BP) lower trunk. METHODS: Fifty-eight adult male Sprague-Dawley rats were randomly divided into 5 groups. Under pentobarbital sodium anesthesia, cobra venom was injected into the lower trunk or sham operation was performed in the animals. On postoperative day 1 and day 12, pregabalin was administered intragastricly at 30 mg/kg in two groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were used to analyze the spontaneous behaviors. Meanwhile, our model was confirmed by observing ultrastructural alterations of the BP and cervical cord (C8-T1) via electron microscope examination. RESULTS: In comparison to the blank and sham-operated group, cobra venom-treated rats showed a profound decrease in the MWT, exploratory and increase in grooming behaviors (P<0.05). The changes were long-lasting (up to 60 days), in both ipsilateral and contralateral paws. Furthermore, it was observed under microscopic examination that the myelin sheath was demyelinated in the BP and cervical cord (C8-T1) after injection of cobra venom to the lower trunk. Pregabalin group rats showed changes in MWT and spontaneous behaviors after pregabalin treatment at postoperative day 1 (P>0.05), compared with the control and sham-operated groups. In pregabalin test POD12 group, the decreased MWT and the increased grooming behavior were improved at 20 days after operation. However, pregabalin had no effect on exploratory activity. Results indicate that pregabalin effectively attenuates mechanical hyperalgesia in acute period. CONCLUSIONS: The cobra venom model can be used as a model to induce neuropathic pain and to enable study of the mechanism and treatment.

A new animal model of trigeminal neuralgia produced by administration of cobra venom to the infraorbital nerve in the rat.

BACKGROUND: Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. RESULTS: The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.

Interventional management for cancer pain.

Cancer pain is a distressing result of disease, both primary and metastatic, as well as complications caused by cancer treatment. Medication management often is insufficient to adequately treat the ensuing pain or the complications of medical management limit acceptable dosage for pain control. In these instances, interventional modalities are an additional tool in the pain physician's armamentarium. Most commonly employed are intrathecal opioids, local anesthetic and clonidine infusions, neurolytic-nerve and sympathetic-ganglion blockade, and radiofrequency techniques. These are discussed in this article concomitantly with current outcome data as reported in the medical literature.

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.

The steroid withdrawal syndrome: a review of the implications, etiology, and treatments.

Steroid therapy is frequently used for chronic pain, particularly inflammatory pain states. Steroid withdrawal syndrome can produce a broad array of signs and symptoms, some of which are not well recognized. High fever is among these. We describe several cases with this clinical scenario and review the syndrome in broader terms.

Quantitative Evaluation of Pain with Pain Index Extracted from Electroencephalogram.

BACKGROUND: The current pain assessment methods are strongly subjective and easily affected by outside influences, and there is an urgent need to develop a reliable objective and quantitative pain-monitoring indicator. The aim of this study was to evaluate the feasibility of using Pain index (Pi) to assess pain symptoms in pain patients. METHODS: Subjects were enrolled from patients seeking treatment at Pain Medicine Center of China Medical University Aviation General Hospital from October 2015 to December 2016, such as postherpetic neuralgia, spinal cord injury, femoral head necrosis, lumbar disc herniation, trigeminal neuralgia, complex regional pain syndrome, perineal pain, phantom limb pain, etc., (pain group, n = 111), as well as healthy volunteers without subjective pain (control group, n = 100). The subjective pain symptoms in pain patients were evaluated by Pi and visual analogue scale/numerical rating scales (VAS/NRS), respectively, and the relationship between them was analyzed using single factor correlation analysis and multiple factor regression analysis. RESULTS: Pi levels in the pain group were significantly higher than those of the control group (t = 6.273, P< 0.001), the correlation analysis of Pi and VAS/NRS score in the pain group showed that the Pearson correlation coefficient was 0.797 (P < 0.001); After adjusted for types of pain, pain sites, medication, gender, and age, Pi was found to be independently correlated to VAS/NRS score (P < 0.001). CONCLUSIONS: Pi significantly correlates with VAS/NRS score, might be used to evaluate the subjective pain symptoms in patients and has good research and application value as an objective pain assessment tool.

Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom.

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 (P<0.05) for the EA group and pregabalin group compared with the cobra venom group; moreover, demyelination of neurons in Gasserian ganglion and medulla oblongata was reversed. The number of platform site crossings, the average percentages of time in the target quadrant and the field excitatory postsynaptic potential slopes increased (P<0.05) in the EA group compared to the cobra venom group. However, the pregabalin group showed no differences compared to the cobra venom group (P>0.05). 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.

Gene therapy and chronic pain.

Chronic, unremitting pain is perhaps the most common reason that patients seek medical care. In general, conservative techniques, such as medical management, are implemented as first-line therapy. Local anesthesia and lytic procedures, followed by interventional techniques, such as dorsal column stimulation and intrathecal drug delivery systems, are second-line therapies. However, for refractory and severe pain, which is not adequately controlled by other modes of therapy, new emerging options, including molecular or gene therapy, may become more widely utilized as experimental results are translated into clinical options.

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.

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.

Higher dose dexamethasone increases early postoperative cognitive dysfunction.

OBJECTIVE: To investigate the effects of intravenous administration of dexamethasone on early postoperative cognitive dysfunction (POCD). METHODS: In this prospective randomized trial, 1000 patients with facial spasm undergoing microvascular decompression (MVD) were randomly assigned to receive normal sodium (Dex-0 group, n=333), dexamethasone 0.1 mg/kg (Dex-1 group, n=333), or dexamethasone 0.2 mg/kg (Dex-2 group, n=334). Exclusion criteria included: a history of neurologic or mental disease, renal failure, active liver disease, cardiac or pulmonary dysfunction, endocrine, metabolic, or peptic ulcer disease, a history of past surgery, <6 years of schooling, inability to complete neuropsychological testing, visual dysfunction, and auditory dysfunction. Patients were also excluded at any point if additional steroid was required. Propofol and sufentanil were administered for anesthetic induction, whereas propofol and remifentanil were given for maintenance of anesthesia. A battery of 9 neuropsychological tests was administered preoperatively and the on day 5 postoperatively. A postoperative deficit was defined as a postoperative decrement to preoperative score of >1SD on any test. Patients who experienced >2 deficits were considered to have experienced early POCD. RESULTS: Nine hundred and fifty-four patients completed both preoperative and postoperative neuropsychological testing. Within the 3 groups: Dex-0 group, n=319; Dex-1 group, n=320 and Dex-2, n=315. POCD occurred in 71 patients (22.3%) in the Dex-0 group, in 66 patients (20.6%) in the Dex-1 group, and 99 patients (31.4%) in the Dex-2 group. POCD was significant among the 3 groups (P=0.003). Partitions of χ method was applied for multiple comparisons showing that Dex-2 group was significantly different from Dex-1 and Dex-0 groups. CONCLUSIONS: Administration of higher dose of dexamethasone (0.2 mg/kg) increases the incidence of POCD in the early postoperative period after microvascular decompression under general anesthesia.

The distance from skin to cervical and high thoracic epidural space on chinese adults as read from MRI.

BACKGROUND: A few studies on the depth from the skin to the cervical epidural space (DSES) have been reported from the United States, South Korea, Japan, and Taiwan. There are no published reports from mainland China. OBJECTIVES: The goal of this study was to collect standard data on Chinese adults from mainland China in a large medical center with a wide geographical range of patients. STUDY DESIGN: A prospective study. SETTING: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: The survey included 410 patients. Measurements were made of DSES, the dural sac, and the spinal cord by automatic measuring ruler on transverse and sagittal images of the cervical spine at the C5-6, C6-7, C7-T1, T1-2, and T2-3 intervertebral space obtained by magnetic resonance imaging (MRI). We also obtained the width of the epidural space by measuring the distance from the (LF) to the dural sac. RESULTS: DSES at C5-6, C6-7, C7-T1, T1-2, and T2-3, respectively, was 4.69 ± 0.84 cm, 5.14 ± 0.98 cm, 5.56 ± 1.03 cm, 5.81 ± 0.94 cm, and 5.76 ± 0.86 cm on T2W (weighted) MRIs obtained in the sagittal plane (mean ± SD). The distance at C5-6, C6-7, and C7-T1 in transverse images was 4.67 ± 0.86 cm, 5.18 ± 1.02 cm, and 5.55 ± 0.97 cm, respectively. All measured distances from the skin to the epidural space were significantly greater in men than in women. Multivariate regression analysis revealed significant partial correlation between DSES and (BMI). LIMITATION: Limitations include the absence of healthy individuals as well as the influence of the difference in neck positioning during the MRI examination vs. active epidural puncture. CONCLUSION: DSES varied with the cervical intervertebral level in those patients studied from the population of mainland China. The greatest DSES was noted at C7-T1 in men and T1-2 in women, and the least was at C5-6 in both men and women. DSES had a significant relationship with neck circumference and BMI in both genders. We suggest that the DSES be measured with MRI before performing epidural puncture. The lower cervical and upper thoracic intervertebral spaces appear to provide a greater margin of safety for epidural puncture.