• The Korean Journal of Pain
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• 제26권3호
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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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• 제17권4호
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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.

• 한국임상수의학회지
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• 제25권2호
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• pp.73-78
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• 2008

케타민은 N-methyl-D-aspartate (NMDA) 수용체의 비경쟁적인 길항제로 인의와 수의학에서 전신 마취제로 사용하는 약물이다. 본 연구진은 이전에 케타민이 개 말초혈액 백혈구의 순간산소과소비현상(oxidative burst activity)을 손상시킨다고 보고하였다. 현재 연구에서는 개 말초혈액 탐식세포의 탐식능(phagocytic capacity)에 대한 케타민의 효과를 검토하였다. 탐식능은 유세포 분석기로 분석하였다. 말초혈액 다형핵백혈구(peripheral blood polymorphonuclear cells; PMN)와 단구(monocytes)의 탐식능은 케타민의 직접 처리에 의해 감소하였으나 단핵구세포(peripheral blood mononuclear cells; PBMC) 분획에서의 탐식능은 케타민의 직접 처리에 의해 변화가 없었다. 말초혈액 다형핵백혈구와 단구의 탐식능은 케타민을 처리한 단핵구세포 배양상층액에 의해서도 감소하였다. 이상의 결과로부터 케타민은 호중구와 단구와 같은 개 말초혈액 탐식세포의 탐식능에 있어 직접적인 억제효과를 나타내며, 또한 케타민 처리 단핵구세포로부터 생산되는 가용성인자에 의해서도 탐식세포의 탐식능이 억제되는 것으로 사료되었다.

• The Korean Journal of Pain
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• 제27권4호
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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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• 제15권1호
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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.

• 한국임상수의학회지
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• 제23권4권
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• pp.393-399
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• 2006

전신마취제인 케타민은 흥분성 아미노산의 활성을 방해하는 N-methyl-D-aspartate (NMDA) 수용체의 비경쟁적인 길항제이다. 본 연구는 개 말초혈액 백혈구의 순간산소과소비현상(Oxidative burst activity; OBA)에 있어서 케타민의 효과를 검토하였다. 탐식세포의 OBA는 유세포 분석기로 분석하였다. 케타민을 말초혈액 다형핵백혈구(peripheral blood polymorphonuclear cells; PMN)와 monocyte-rich cells에 직접처리 하였을 때는 OBA가 감소하였으며, 또한 케타민을 처리한 말초혈액 단핵구세포(peripheral blood mononuclear cells; PBMC) 배양상층액에 의해서도 PMN과 monocyte-rich cells의 OBA가 감소하였다. 그러나 케타민을 처리한 PMN 배양상층액에 의해서는 탐식세포의 OBA에 있어서 아무런 변화가 없었다. 하지만 이러한 OBA의 감소는 latex beads를 넣어 탐식반응이 일어날 때만 측정되었다. 이상의 결과로부터 탐식반응이 일어나는 동안 케타민은 호중구와 단핵구와 같은 개 말초혈액 탐식구의 OBA에 있어 억제효과를 나타내었다.

• Journal of Hospice and Palliative Care
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• 제19권3호
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• pp.249-255
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• 2016

목적: 췌장암 환자의 90% 이상이 신경성 통증을 앓는 것으로 알려져 있으며 말기 췌장암 환자에서는 통증조절이 매우 중요한 목적 중 하나이다. 케타민은 NMDA 수용체 길항제로서 신경통에 효과가 있는 것으로 알려져 있으며 마약성 진통제의 요구를 감소시켜주는 효과에 대한 연구들이 앞서 진행된 바 있는 약물이다. 본 연구에서는 완화병동에 입원한 췌장암 환자들을 대상으로 케타민의 사용과 관련된 항목들을 알아보고 마약성 진통제를 줄여주는 효과를 나타내는지에 대해 진행한 연구이다. 방법: 2013년 1월부터 2014년 12월까지 서울성모병원완화의학과에 입원한 췌장암 환자 111명에 대한 의무기록을 통하여 케타민을 사용한 그룹(34명)과 사용하지 않은 그룹(77명)에 대해 케타민 사용과 관련된 요인 및 사용 후 모르핀을 포함한 마약성 진통제의 용량 변화를 분석하였다. 결과: 케타민을 사용한 군에서 사용하지 않은 군에 비하여 총 기본 마약성 진통제 사용량(P value 0.001), 하루에 사용한 마약성 진통제의 용량(P value<0.001), 평균 구제 약물의 용량(P value 0.001), 하루 평균 구제 약물 사용 횟수(P value 0.001), 하루 평균 구제 약물을 용량(P value<0.001)이 더 높게 나타났다. 케타민 사용 전후를 비교한 결과 마약성 진통제는 케타민 사용 전(76.1 (${\pm}64.5$))에 비하여 후(89.6 (${\pm}80.9$))에 유의하게 증가한 것으로 확인되었다. 결론: 후향적으로 의무기록 분석을 통해 이루어진 본 연구에서는 더 많은 용량의 마약성 진통제를 요한 환자들이 케타민을 사용한 경향이 확인되었다. 이와 더불어 케타민을 사용함으로 인해 마약성 진통제 요구량이 감소하는 경향은 확인할 수 없었다. 차후 더 많은 환자들과 다양한 종류의 암성 통증을 대상으로 한 완화의료적 목적의 케타민 사용에 대한 연구가 요할 것으로 생각되며 케타민의 사용에 관련된 가이드라인에 대한 논의가 요할 것으로 생각된다.