• Korean Journal of Veterinary Research
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• v.33 no.3
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• pp.361-368
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• 1993

The midbrain periaqueductal gray is a midline structure that encircles the mesencephalic aqueduct of midbrain and plays an important role in anaglgesia and modulation of nociceptive input to the central nervous system. It has been demonstrated that the periaqueductal gray contains several neuropeptides including neurotensin, which has been postulated antinociceptive effect to the periaqueductal gray. The present study was performed to provide immunohistochemical localization of neurotensin of midbrain periaqueductal gray in the Korean native goat by using immunohistochemical method. Neurotensin-like immunireactive neurons were localized throughout the midbrain periaqueductal gray, although more immunoreactive neurons were present in the middle and caudal parts of periaquductal gray than the rostral part. Dense neurotensin-like immunoreactive neurons were much more numerous in the ventral lateral division of the mid- and caudal periaqueductal grays. Neurotensin-like immunoreactive neurons were much larger and more prominent near the external margin of the gray than in the juxta-aqueductal region. Neurotensin-like immunoreactive fibers were observed as short processes extending from immunoreactive cells and some small immunoreactive puncta and varicose-like fibers were also seen.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.34-42
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• 2003

This study was designed to investigate the modulation of the Corydalis tuber on glycine-activated ion current in rat periaqueductal gray (PAG) neurons. Aqueous extract from Corydalis tuber has been widely used for pain control such as dysmenorrhea, irregular menstruation or amenorrhea with abdominal cramping, neuralgia, headache and gastrointestinal spasm. The PAG region of the brain is known to be involved heavily with nociception. Modulation of the Corydalis tuber on glycine-induced ion current in rat periaqueductal gray (PAG) neurons was studied by a nystatin-perforated patch-clamp technique. High concentrations of Corydalis tuber elicited ion current, which was suppressed by strychnine application. Low concentrations of Corydalis tuber reduced glycine-induced ion currents in the PAG neurons. Inhibitory action of Corydalis tuber on glycine-activated ion current was reduced by treatment with naltrexone, a non- selective opioid antagonist. Application of N-methylmalemide (NEM), a sulfhydryl alkylating agent, also reduced the inhibitory action of Corydalis tuber on glycine-activated ion current in the PAG neurons. These results suggest that the inhibitory effect of Corydalis tuber on glycine-activated ion current in the PAG neurons is one of the analgesic mechanisms of the Corydalis tuber, which may activate descending pain control system in PAG neurons.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.549-555
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• 2008

Bupleuri radix (Umbelliferae), the dried root of Bupleurum Chinense DC, has been clinically used to mitigate pain sensation. The descending pain control system consists of three major components, and modulation of pain in the periaqueductal gray is the most extensively studied descending pain control system. However, the relation of Bupleuri radix on the descending pain control system has not been clarified. In the present study, modulation of the aqueous extract of Bupleuri radix on glycine-induced ion current in the acutely dissociated periaqueductal gray neurons was investigated by using nystatin-perforated patch-clamp technique under voltage-clamp condition. In the present results, the glycine-induced ion current was significantly suppressed by 0.1 mg/ml Bupleuri radix, while treatment with $10^{-5}\;M$ naltrexone, opioid receptor antagonist, alleviated Bupleuri radix-induced inhibition on glycine-induced ion current. The present study showed that the aqueous extract of Bupleuri radix may activate descending pain control system through inhibition on glycine-induced ion current in the periaqueductal gray neurons and this effect is mediated by opioid receptors.

• Korean Journal of Veterinary Research
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• v.38 no.4
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• pp.720-729
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• 1998

Immunohistochemical technique of the c-fos primary gene protein, Fos, was used to analyze the effects of external factors on the neuronal activities in the periaqueductal gray(PAG) of the intact rats, sham-operated rats and post-operated stress control rats. In addition, the number of Fos positive neurons has been evaluated to verify the effects of cannula implantation and veratridine treatment on the neuronal activities in PAG area. The results were summerized as follow : 1. There was no significant difference in the number of Fos positive neurons observed in the caudal and middle portion of lateroventral PAG from cannula implanted rats and sham operated rats. 2. The number of Fos positive neurons in the PAG was not changed by the stress induced by connection of collecting tube to rats for 12 hours as compared to that of intact rats. 3. In the saline treated group, the Fos immunoreactivity in the PAG did not changed at 30 minutes and 1 hour after saline treatment as compared to that of intact rats. However, the number of Fos positive neurons was significantly increased at 2 hours after treatment compared to that of saline treated rats at 30 minutes after treatment. 4. The Fos immunoreactivity was dramatically increased at 30 minutes, 1 hour and 2 hours after veratridine treatment as compared to those of saline treated groups. The number of Fos immunoreative neurons showed the maximal level at 2 hours after veratridine treatment. 5. The Fos positive neurons induced by saline and veratridine treatment were mainly distributed in front of the microdialysis window. These results suggest that new microdialysis demonstrated in this study improves efficiency and accuracy to confine the neuronal activity in front of microdialysis window site. Moreover, this directional specificity allows us to locate probe tips adjacent to the brain area of the interest site rather than centering the probes within that brain area. Finally, This microdialysis method can be used to dialyse the neurotransmitters using concious and freely moving rats.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.116-124
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• 2006

Peripheral nerve injuries are a commonly encountered clinical problem and often result in chronic pain and severe functional deficits. At the Dept. of Oriental Rehab. Medicine, we have used for pain control a herbal bath containing the following herbs: Harpagophytum radix, Atractylodes japonica and Corydalis tuber. In the present study, we investigated the effects of this herbal bath on the recovery rate of the locomotor function and the expression of c-Fos in the ventrolateral periaqueductal gray (vIPAG) region of the brain following sciatic crushed nerve injury in rats. In the present study, characteristic gait change with decreasing of the sciatic function index (SFI) was observed and c-Fos expression in the vIPAG was suppressed following sciatic crushed nerve injury in rats. Immersion into herbal bath enhanced SFI value and restored c-Fos expression in the vIPAG to the control value. These results suggest the herbal bath might activate neurons in the vIPAG, and could facilitate functional recovery from peripheral nerve injury.

• The Journal of Korean Medicine
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• v.28 no.4
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• pp.104-113
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• 2007

Background : Amygdalin is abundant in Armeniacae semen, and it is recently reported to treat cancers and relieve pain. But modus operandi of amygdalin at the level of neuron has not been reported, yet. Objective : This study aimed to find out the effect of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons. And it was investigated that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. Method : We investigated that the changes of glycine- and glutamate-induced ion currents in PAG neurons through application of lipopolysaccharides (LPS) and application of amygdalin with LPS by using the nystatin-perforated patch clamp method. Result : Application of LPS on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamate-induced ion current decreased by LPS. Conclusion : Amygdalin from Armeniacae semen controls glycine- and glutamate-induced ion current by LPS in PAG neurons, and it is suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons.

• Korean Journal of Acupuncture
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• v.20 no.4
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• pp.17-29
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• 2003

목적:천수근은 염증성 관절염과 염증성 장 질환 등에 사용되어왔다. 천수근이 중심회백질 신경세포에서 하행성 진통작용에 미치는 영향을 연구하였다. 방법: 중심회백질 신경세포를 분리하여 전위고정하에서 nystatin-perforated patch-clamp technique을 시행하였다. 결과: 천수근에 의하여 유발되는 이온전류는 GABA, glycine, 그리고 glutamate 수용체를 모두 활성화시켰다.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.556-563
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• 2008

Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. The expression of c-Fos is sometimes used as a marker of increased neuronal activity. We have prepared the aqueous extract of amygdalin from Armeniacae semen for pain control. In the present study, we investigated the effects of amygdalin on the recovery rate of the locomotor function and on the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used in this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Amygdalin enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. The present our study indicated that amygdalin activates neurons in the vlPAG, and it facilitates functional recovery following peripheral nerve injury.

• The Korean Journal of Pain
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• v.34 no.2
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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.

• Journal of Integrative Natural Science
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• v.15 no.2
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• pp.63-72
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• 2022

To elucidate the neurochemical characteristics of the midbrain periaqueductal gray (PAG), the distribution patterns of several neuroanatomical markers within the PAG were compared. Immunohistochemical staining for the intracellular calcium binding proteins including calbindin, calretinin, and parvalbumin and histochemical staining for cytochrome oxidase, acetylcholinesterase, and NADPH-diaphorase were performed in. Each chemical substance were localized in the specific subregions within PAG. Calbindin- immunoreactivity were selectively distributed in the dorsolateral PAG, the ventral half of lateral PAG, the ventralateral PAG, and supraoculomotor cap (Su3C) nucleus. Distribution of calretinin-immunoreactivity were generally similar with that of clabindin, but showed relatively low subregional selectivity. Parvalbumin-immunoreactivity was very poor within the PAG. High reactivity of cytochrome oxidase were found in the dorsomedial PAG and the lateral half of lateral PAG, in which calbindin- and calretinin-immunoreactive perikarya were scarcely observed. Acetylcholinesterase distribution was similar with that of cytochrome oxidase, and the difference was in the additional marking of of Su3C with acetylcholinesterase. Results of the present study provides data for the further subdivisions of the territory of the PAG compared to the presently accepted subregions within the PAG.