• Journal of Oral Medicine and Pain
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• 제38권2호
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• pp.215-219
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• 2013

하행성 억제계란 중뇌, 연수, 뇌교에 존재하는 해부학적 유해수용 조절성 기전을 일컫는 용어이다. 이들 부위를 전기적으로 자극을 하면 진통효과가 나타나며, 하행성 억제계의 실패시 지속적인 통증이 야기된다는 것을 알 수 있다. 또한 우울불안 같은 질환은 만성 신경병성 통증 상태로 쉽게 진행됨이 밝혀졌다. 이러한 요인들이 만성 신경병성 통증에 영향을 주는 경로는 아마도 하행성 억제계일 가능성이 있다. 흥미롭게도, 광범위하게 하행성 억제계가 작동하지 않을 경우 과민성 대장증상이 호발하는 것으로 보인다. 또한 이러한 환자들은 높은 불안, 우울 지수가 관찰되기도 한다. 다양한 연구에서, 하행성 억제계에 관여하는 ${\alpha}2$ 아드레날린성 약물, 아편유사약물들이 만성 통증에 사용될 수 있음을 동물에서 평가 중이다. 아직 신체내에서 얼마나 하행성 억제계가 일어나고 있는가에 대해서는 임상적으로 증명하기 힘든 감이 있지만, 여러 감각 신경기전의 수정에 중요한 구실을 하고 있는 것으로 믿어진다. 즉 중추신경계는 대상을 인식하기 위해 말초정보를 받아들이는 기능만 있는 것이 아니라 여러 방법으로 정보의 홍수를 조절하고 선택하는 기능을 동시에 갖추고 있는 것으로 생각된다.

• 대한한의학회지
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• 제41권4호
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• pp.88-99
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• 2020

Objectives: The purpose of this study is to investigate the mechanism of acupuncture for treating chemotherapy-induced peripheral neuropathy. Methods: Based on domestic and international papers reported until October 2020, experimental papers on "chemotherapy induced peripheral neuropathy", "mechanism", and "acupuncture" were set up to identify the mechanisms of chemotherapy induced peripheral neuropathy. A total of seven papers were selected and searched: one pilot paper for people and six experimental papers for rats. Results: In the pilot paper studied by Bao, T., the effect of EA was demonstrated but no significant results were produced for the mechanism. Moon et al. derived the association between EA and plasma 𝛽-endorphin in rat experimental studies on oxalilatin-induced cold hypersensitivity. Meng et al. found relevance to 𝜇, 𝛿, and 𝛿 opioid through EA stimulation in paclitaxel-induced peripheral neuropathy. Lee et al. studied the relationship between EA and muscarin and 5-HT in rat experiments on oxaliplatin-induced coldness, associated with 5-HT and EA, especially with 5-HT3 receptors. Choi et al. revealed the association of adrenaline and opioid acting on 𝛼2- and 𝛽 adrenaline receptors with EA in rat experiments on paclitaxel-induced neuralgia. In rat experiments on oxaliplatin-induced neuralgia reported by Lee, 𝛽-endorphin and encephalin were studied to be mediated by EA. Zhang, T. et al. revealed in the paclitaxel induced rat experiment that EA activates 5-HT. Conclusion: It is inferred that peripheral neuropathy caused by anticancer drugs can be reduced by activating the action of 5-HT, 𝛽-endorphin, and encephalin through the descending inhibitory pathways. cell differentiation, herbal medicine, Pongamia, stem cells

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.661-670
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• 1998

Dopamine has been generally known to exert antinociceptive action in behavioral pain test, such as tail flick and hot plate test, but there appears to be a great variance in the reports on the antinociceptive effect of dopamine depending on the dosage and route of drug administration and type of animal preparation. In the present study, the effects of dopamine on the responses of wide dynamic range (WDR) cells to mechanical, thermal and graded electrical stimuli were investigated, and the dopamine-induced changes in WDR cell responses were compared between animals with an intact spinal cord and the spinal animals. Spinal application of dopamine (1.3 & 2.6 mM) produced a dose-dependent inhibiton of WDR cell responses to afferent inputs, the pinch-induced or the C-fiber evoked responses being more strongly depressed than the brush-induced or the A-fiber evoked responses. The dopamine-induced inhibition was more pronounced in the spinal cat than in the cat with intact spinal cord. The responses of WDR cell to thermal stimulation were also strongly inhibited. Dopamine $D_2$ receptor antagonist, sulpiride, but not $D_1$ receptor antagonist, significantly blocked the inhibitory action of dopamine on the C-fiber and thermal responses of dorsal horn cells. These findings suggest that dopamine strongly suppresses the responses of WDR cells to afferent signals mainly through spinal dopamine $D_2$ receptors and that spinal dopaminergic processes are under the tonic inhibitory action of the descending supraspinal pathways.

• The Korean Journal of Pain
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• 제11권1호
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• pp.23-29
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• 1998

Background: The present study was conducted to investigate effects of microinjection of bicuculline, GABA-A receptor antagonist, into the brain stem nuclei on the dorsal horn neuron responsiveness in rats with an experimental peripheral neuropathy. Methods: An experimental neuropathy was induced by a unilateral ligation of L5~L6 spinal nerves of rats. After 2~3 weeks after the surgery, single-unit recording was made from wide dynamic range (WDR) neurons in the spinal cord dorsal horn. Results: Responses of WDR neurons to both noxious and innocuous mechanical stimuli applied to the somatic receptive fields were enhanced on the nerve injured side. These enhanced responsiveness of WDR neurons were suppressed by microinjection of bicuculline into periaqueductal gray(PAG) or nucleus reticularis gigantocellularis(Gi). A similar suppression was also observed when morphine was microinjected into PAG or Gi. Suppressive action by Gi-bicuculline was reversed by naloxonazine, ${\mu}$-opioid receptor antagonist, microinjected into PAG whereas PAG-bicuculline induced suppression was not affected by naloxonazine injection into Gi. Gi-bicuculline induced suppression were reversed by a transection of dorsolateral funiculus(DLF) of the spinal cord. Conclusions: The results suggest that endogenous opioids, via acting on GABAergic interneurons in PAG and Gi, may be involved in the control of neuropathic pain by activating the descending inhibitory pathways that project to the spinal dorsal horn through DLF to inhibit the responsiveness of WDR neurons.

• The Korean Journal of Pain
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• 제34권2호
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• pp.176-184
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• 2021

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions: Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.687-693
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• 1998

This study was performed to examine the mean arterial pressure and nociceptive jaw opening reflex after microinjection of glutamate into the amygdala in freely moving rats, and to investigate the mechanisms of antinociceptive action of amygdala. Animals were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula (26 gauge) was implanted in the amygdala and lateral ventricle. Stimulating and recording electrodes were implanted into each of the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. After 48 hours of recovery from surgery, mean arterial pressure and digastric electromyogram (dEMG) were monitored in freely moving rats. Electrical shocks (200 ${\mu}sec$ duration, $0.5{\sim}2$ mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minutes. After injection of 0.35 M glutamate into the amygdala, mean arterial pressure was increased by $8{\pm}2$ mmHg and dEMG was suppressed to $71{\pm}5%$ of the control. Injection of 0.7 M glutamate elevated mean arterial pressure by $25{\pm}5$ mmHg and suppressed dEMG to $20{\pm}7%$ of the control. The suppression of dEMG were maintained for 30 minutes. Naloxone, an opioid receptor antagonist, inhibited the suppression of dEMG elicited by amygdaloid injection of glutamate from $28{\pm}4\;to\;68{\pm}5%$ of the control. Methysergide, a serotonin receptor antagonist, also inhibited the suppression of dEMG from $33{\pm}5\;to\;79{\pm}4%$ of the control. However, phentolamine, an ${\alpha}-adrenergic$ receptor antagonist, did not affect the suppression of dEMG. These results suggest that the amygdala can modulate both cardiovascular and nociceptive responses and that the antinociception of amygdala seems to be attributed to an augmentation of descending inhibitory influences on nociceptive pathways via serotonergic and opioid pathways.

• Journal of Yeungnam Medical Science
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• 제39권3호
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• pp.200-205
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• 2022

Pain from nervous or musculoskeletal disorders is one of the most common complaints in clinical practice. Corticosteroids have a high pain-reducing effect, and their injection is generally used to control various types of pain. However, they have various adverse effects including flushing, hyperglycemia, allergic reactions, menstrual changes, immunosuppression, and adrenal suppression. Pulsed radiofrequency (PRF) is known to have a pain-reducing effect similar to that of corticosteroid injection, with nearly no major side effects. Therefore, it has been widely used to treat various types of pain, such as neuropathic, joint, discogenic, and muscle pain. In the current review, we outlined the pain-reducing mechanisms of PRF by reviewing previous studies. When PRF was first introduced, it was supposed to reduce pain by long-term depression of pain signaling from the peripheral nerve to the central nervous system. In addition, deactivation of microglia at the level of the spinal dorsal horn, reduction of proinflammatory cytokines, increased endogenous opioid precursor messenger ribonucleic acid, enhancement of noradrenergic and serotonergic descending pain inhibitory pathways, suppression of excitation of C-afferent fibers, and microscopic damage of nociceptive C- and A-delta fibers have been found to contribute to pain reduction after PRF application. However, the pain-reducing mechanism of PRF has not been clearly and definitely elucidated. Further studies are warranted to clarify the pain-reducing mechanism of PRF.

• The Korean Journal of Pain
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• 제36권1호
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• pp.113-127
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• 2023

Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between painmodulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life. Methods: This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group. Results: Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63-0.94) to discriminate who does/does not respond to the CPM-test. Conclusions: These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.307-312
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• 1998

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 ${\mu}sec$ duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of $15\;{\mu}g$ imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to $76{\pm}6%$ control. Intracisternal administration of $30\;{\mu}g$ desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to $48{\pm}2,\;27{\pm}8,\;or\;25{\pm}5%$ of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from $23{\pm}2\;to\;69{\pm}4%,\;from\;32{\pm}5\;to\;80{\pm}9%,\;and\;from\;24{\pm}6\;to\;77{\pm}5%$ of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

• 지질공학
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• 제24권4호
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• pp.525-534
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• 2014

폐광 부지에서 발생하는 대표적인 환경 문제는 산성으로 오염된 지표수와 지하수, 적재된 폐광석 및 광미, 채굴 활동으로 야기된 지반침하 현상을 들 수 있다. 이 논문은 광해 유형에 따라 재해 및 오염영역을 효율적으로 탐지했던 지구물리탐사방법들을 고찰하는데 있다. 시험 자료로서 토양오염, 산성광산배수, 지반침하, 인공차수막 파손 및 광미/폐광석 적치장을 각각 대표하는 네 개의 폐광 부지를 선택하였다. 자료 검증을 위해 물리탐사자료는 자료의 유형에 따라 시추자료(코어 샘플, 물리검층, 토모그래피 등)와 물 자료(수소이온농도, 전기전도도, 중금속원소 등)와 비교하였다. 토양오염 탐지에 있어서 낮은 전기비저항 이상대는 특히 구리, 납, 아연의 중금속 농도가 높은 지역과 부합된다. 산성광산배수의 유동 경로는 자연전위 곡선에서 음의 전위 이상대, 전기비저항자료에서의 저비저항 이상대, 지하레이더 자료에서의 얕은 투과깊이 영역으로 탐지되었다. 채굴적은 전기비저항 단면에서의 저비저항 이상대, 탄성파토모그래피에서 낮은 속도 영역, 물리검층곡선의 복합해석으로 특징되며, 정확한 위치는 코어자료와 시추공영상자료에서 잘 확인되었다. 침출수 유동을 차단하기 위해 설치된 인공차수막의 파손 구간은 전기비저항 자료에서의 국부적인 이상대로 정확히 탐지되며 매립된 폐석더미는 고비저항 이상대와 저속도 이상대로 특징된다.