• Interdisciplinary Bio Central
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• 제2권4호
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• pp.9.1-9.5
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• 2010

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

• The Korean Journal of Pain
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• 제37권2호
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• pp.107-118
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• 2024

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

• Molecules and Cells
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• 제25권2호
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• pp.149-157
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• 2008

Dopamine is a major neurotransmitter in the mammalian central nervous system (CNS) that regulates neuroendocrine functions, locomotor activity, cognition and emotion. The dopamine system has been extensively studied because dysfunction of this system is linked to various pathological conditions including Parkinson's disease, schizophrenia, Tourette's syndrome, and drug addiction. Accordingly, intense efforts to delineate the full complement of signaling pathways mediated by individual receptor subtypes have been pursued. Dopamine D1-like receptors are of particular interest because they are the most abundant dopamine receptors in CNS. Recent work suggests that dopamine signaling could be regulated via dopamine receptor interacting proteins (DRIPs). Unraveling these DRIPs involved in the dopamine system may provide a better understanding of the mechanisms underlying CNS disorders related to dopamine system dysfunction and may help identify novel therapeutic targets.

• 약학회지
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• 제33권6호
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• pp.333-338
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• 1989

It has been postulated that abnormal characteristics of central noradrenergic nervous system has been implicated in the development and maintenance of hypertension in several modes of experimental hypertension including spontaneously hypertensive rats (SHR). In the present study, we attempt to determine if abnormal characteristics of central noradrenergic nervous system in SHR is caused by genetic factors or hypertensive phenomena by evaluating the changes of central adrenoceptors after long-term treatment of clonidine. Animals were divided into three groups; (1) 14 week-old SHR; (2) age-matched normotensive Wistar rats (NW); (3) DOCA-Salt induced hypertensive rats (DS). Clonidine (100 ug/kg) or vehicle was injected intraperitonealy twice a day for 15 days. Changes of ${\alpha}_1-$ and ${\alpha}_2-receptor$ desities following clonidine treatment were determiend in frontal corte, medulla oblongata and hypothalamus using 3H-WB4101 and 3H-clonidine, respectively. Densities of ${\alpha}_1$ and ${\alpha}_2-receptors$ following clonidine treatment were not changed in frontal cortex and medulla oblongate of SHR as well as DS, but increased in frontal cortex of NW and decreased in medulla oblongata of NW. On the other hand, densities of ${\alpha}_1-receptors$ were increased and densities of ${\alpha}_2-receptors$ were not changed in hypothalamus of SHR but densities of ${\alpha}_1-$ and ${\alpha}_2-receptors$ were decreased in hypothalamus of DS as well as NW. These results suggest that such differences in frontal cortex and medulla oblongata of SHR may be results of hypertensive phenomena whereas those in hypothalamus may be relevant to genetic factors of SHR.

• 대한임상독성학회지
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• 제5권1호
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• pp.36-42
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• 2007

Purpose: To assess the epidemiology and the clinical features of Glufosinate herbicide in Korea. Methods: Data was prospectively collected during 1 year since August 2005 from 38 hospital in Korea. We analyzed the epidemiologic characters and clinical manifestations of Glufosinate poisoning. In addition, the characteristics of patients with severe central nervous system toxicity were separately analyzed to find poor prognosis relating factors. Results: During study periods, there were 715 persons of poisoning of herbicides and insecticides. 6.3% (45 persons) of the agricultural chemicals poisoning had Glufosinate poisoning. There were 36 cases of suicide attempts and 7 cases of accidental exposure, The major of poisoning route was oral ingestion (44 cases). 28.9 % of the study patients had not toxic symptoms. The most common symptoms were gastrointestinal symptoms relating surfactant irritation. 67.7% of central nervous symptoms occurred lately. 10 persons showed severe central nervous system toxicity. 4 persons of them showed poor outcomes (1 death, 3 hopeless discharged). Complications of respiratory failure and renal failure related with poor outcome. Conclusion: Majority of patients ingested Glufosinate for suicide attempt. 22.2% of patients with Glufosinate poisoning showed delayed serious central nervous system toxicity. Early supportive care of altered mentality may prevent late respiratory complications and improve the outcomes.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.75-75
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• 1993

The general pharmacological profiles of SKI 2053R were investigeted on the central nervous system, autonomic nervous system, respiratory-cardiovascular system, digestive system and other systems. SKI 2053R had no significant pharmacological effects. Pharmacokinetic studies on time-course of blood levels, tissue distribution and excretion of SKI 20S3R were performed in rats and beagle dogs after intravenous administration of $^{14}$ C-labeled SKI 2053R. The blood level of radioactivity decreased in bi-or tri-exponential manners: rapidly decreased at $\alpha$-phase but slowly decreased at $\beta$-or ${\gamma}$-phase. $^{14}$ C SKI 2053R was well distributed to all tissues except central nervous system. Tissue concentration profiles of radioactivity were almost consistent wi th those of blood, but higher than those of plasma from 1 to 168 hrs after administration. Also, these results were consistent wi th those of whole body ARG study. The urinary and fecal excretions of radioactivity within 168 hr after administration were 84-87 and 9-11 ％ of total radioactivity of $^{14}$ C-SKI 2053R administered. In lactating rats, the levels of radioactivity in the milk were significantly lower than that in the blood, but slightly higher than that in the plasma. The disapperance of the radioactivity from the milk was similar as that in the plasma.

• The Korean Journal of Pain
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• 제35권3호
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• pp.327-335
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• 2022

Background: The pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP. Methods: Twenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire. Results: FM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although nonsignificant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities. Conclusions: ANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.

• Transactions on Control, Automation and Systems Engineering
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• 제4권1호
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• pp.43-48
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• 2002

We show that humans execute the postural control ingeniously by regulating the impedance properties of the musculo-skeletal system as the motor command against the alteration of the environment. Adjusting muscle activity can control the impedance properties of the musculo-skeletal system. To quantify the changes in human arm viscoelasticity on the vertical plane during interaction with the environment, we asked our subject to hold an object. By utilizing surface electromyographic(EMG) studies, we determined a relationship between the perturbation and a time-varying muscle co-activation. Our study showed when the subject lifts the object by himself the muscle stiffness increases while the torque remains the same just before the lift-off. These results suggest that the central nervous system(CNS) simultaneously controls not only the equilibrium point(EP) and the torque, but also the muscle stiffness as themotor command in posture control during the contact task.

• 한국산학기술학회논문지
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• 제12권11호
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• pp.5019-5026
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• 2011

본 연구는 만성 편마비 환자의 교감신경 활동 강화가 근 긴장도 및 중추신경 흥분성 변화에 미치는 영향을 알아보기 위해 시행하였다. 연구기간은 2009년 10월 12일부터 12월 4일까지 실시하였으며, 연구대상자는 발병 후 6개월 이상 된 만성 편마비 환자 30명을 대상으로 하였다. 실험은 교감신경 활동을 강화하는 세 가지 과제(암산, 정적인 상태에서 쥐기운동, 쥐기운동 후 허혈)를 실시하였으며 측정은 과제를 수행하기 전과 중의 global synkinesis 수준과 중추신경원 활동전위을 각각 측정하였다. 중추신경원 활동전위는 H/Mmax비, V/Mmax비를 측정하였고, global synkinesis 수준은 근전도 활동전위의 실효치 값을 측정하여 분석하였다. 본 연구에서, global synkinesis 수준은 정적인 상태에서 쥐기 과제를 제외한 나머지 과제(암산, 쥐기 후 허혈)에서 슬관절 굴곡, 신전 시 감소했다(p<.05). 또한 V/Mmax비에서는 세 가지 과제 모두에서 감소하였다(p<.05). 결론적으로, 교감신경 활동 강화는 만성 편마비 환자의 중추신경 흥분성과 근 긴장도를 감소시킴을 알 수 있었다.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• 제61권11호
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• pp.567-572
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• 2018

The sensory function of the trigeminal nerve is to provide tactile, proprioceptive, and nociceptive afference by chemical stimulation. Various physical responses of the trigeminal nerve to stimuli help to defend against harmful substances. Recently, many studies have been conducted on solitary chemoreceptor cells innervated by trigeminal nerve. Most volatile organic compounds stimulate both the olfactory and trigeminal nervous systems. In general, the trigeminal nervous system is less sensitive than the olfactory nervous system. Studies have shown that sensation of the trigeminal nerve by chemical stimulation results in inhibition of olfaction. This indicates that the olfactory and trigeminal nerves interact with each other in the central nervous system. It is important to study various noxious stimuli acting on the trigeminal nerve in modern society where environmental concerns are intensifying.