• The Korean Journal of Pain
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• v.26 no.3
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• pp.255-264
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• 2013

Background: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. Methods: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. Results: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. Conclusions: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.

• Journal of Acupuncture Research
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• v.17 no.4
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• pp.5-17
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• 2000

To research the characteristics of ion currents induced by Bujaijung-tang and Bojungikgi-tang, nystatin-perforated patch clamp technique under voltage-c(amp condition was used. Periaqueductal gray neuron was dissociated from Sprauge-Dawley rat, 10-15 days old. Cytotoxicity of Bujaijung-tang and Bojungikgi-tang showed incubation time and concentration dependent manner. Ion current activated by Bujaijung-tang and Bojungikgi-tang were inhibited by bicuculline and strychnine and CNQX. It can be suggested that Bujaijung-tang and Bojungikgi-tang modulate inhibitory and excitatory neurotransmitters-, GABA, glycine and non-NMDA, acticvated ion channels. Modulatory effect of Bujaijung-tang and Bojungikgi-tang was more greater in inhibitory neurotransmitters. Low concentration of Bujaijung-tang which dose not elicit ion current itself, activated GABA and glycine induced chloride currents. In this study, we can found that the activation of Bujaijung-tang and Bojungikgi-tang on non-NMDA subtypes of glutamate receptor is its major action mechanism and can be used as very effective Herb treatment on Myasthenia gravis patient.

• Journal of Veterinary Clinics
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• v.25 no.2
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• pp.73-78
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• 2008

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and a short-acting general anaesthetic agent for human and veterinary use. We previously reported that treatment with ketamine impairs oxidative burst activity of canine peripheral blood leukocytes. In this study, the effect of ketamine on phagocytic capacity of canine peripheral blood leukocytes was examined in vitro. Phagocytic capacity was analyzed by using a flow cytometry. Ketamine directly decreased the phagocytic capacity of peripheral blood polymorphonuclear cells (PMN) and monocytes but not total peripheral blood mononuclear cells (PBMC). In addition, the phagocytic capacity of PMN and monocytes was inhibited by the ketamine-treated PBMC but not PMN culture supernatant. These results suggest that ketamine has a direct inhibitory effect on the phagocytic capacity of canine peripheral blood phagocytes and involves the production of soluble factor(s) from canine PBMC, which may suppress the phagocytic capacity.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.326-333
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• 2014

Background: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.393-399
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• 2006

Ketamine, one of general anesthetics for human and veterinary use, is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids. It has been reported to impair various leukocyte functions. In this study, the effect of ketamine on the oxidative burst activity (OBA) of canine peripheral blood leukocytes was examined. The OBA of canine peripheral blood phagocytes was analyzed by flow cytometry system. Ketamine at higher concentration such as $1,000{\mu}M$ exhibited a low viability of leukocytes. Thus, ketamine was used at concentration of 10 to $500{\mu}M$ showing no cytotoxic effect and high cell viability. The OBA of leukocytes in the presence or absence of latex beads was analyzed by addition of dihydrorhodamine 123. The direct treatment of ketamine revealed the inhibitory effect on the OBA of peripheral blood polymorphonuclear cells (PMN) and monocyte-rich cells but not peripheral blood mononuclear cells (PBMC) in the presence of latex beads. However, when latex beads were not added to PMN, its OBA was not inhibited by ketamine. The OBA of PMN and monocyte-rich cells but not PBMC in the presence of latex beads was also inhibited by culture supernatant from ketamine-treated- PBMC but not -PMN. But the OBA of PMN in the absence of latex beads was not inhibited by culture supernatant from PBMC treated with ketamine. Therefore, these results suggested that ketamine has the inhibitory effect on the OBA of canine peripheral blood phagocytes such as neutrophils and monocytes during phagocytic response.

• Journal of Hospice and Palliative Care
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• v.19 no.3
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• pp.249-255
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• 2016

Purpose: Up to 90% of pancreatic cancer patients suffer from neuropathic pain. In a palliative care setting, pain control in pancreatic cancer patient is one of the major goals. Ketamine is a N-methyl-D-aspartate (NMDA) receptor antagonist, effective in neuropathic pain. Additionally, there have been studies about the opioid sparing effect of ketamine. This study was held in the palliative care unit among pancreatic cancer patients to determine the factors related to ketamine use and the opioid sparing effect. Methods: The medical records of pancreatic cancer patients admitted to St. Mary's hospital palliative care unit between January, 2013 and December, 2014 were reviewed. Patients were divided into 2 categories according to ketamine use. Also, opioid use before and after ketamine use was compared in the ketamine group. Results: Compared to the non-ketamine use group, patients in the ketamine group required a higher dose of opioid. The total opioid dose, daily opioid dose, number of daily rescue medications, and daily average rescue dose were statistically significantly higher in the ketamine group. The opioid requirement was increased after ketamine administration. Conclusion: In this retrospective study, ketamine was frequently considered in patients with severe pain, requiring higher amount of opioid. Studies about palliative use of ketamine in a larger number of patients with diverse types of cancer pain are required in the future.