• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.640-651
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• 2022

Clinical studies on neuromodulation intervention for trigeminal neuralgia have not yet shown promising results. This might be due to the fact that the pathophysiology of chronic trigeminal neuropathy is not yet fully understood. Chronic trigeminal neuropathy includes trigeminal autonomic neuropathy, painful trigeminal neuropathy, and persistent idiopathic facial pain. This disorder is caused by complex abnormalities in the pain processing system, which is comprised of the affective, emotional, and sensory components, rather than mere abnormal sensation. Therefore, integrative understanding of the pain system is necessary for appropriate neuromodulation of chronic trigeminal neuropathy. The possible neuromodulation targets that participate in complex pain processing are as follows : the ventral posterior medial nucleus, periaqueductal gray, motor cortex, nucleus accumbens, subthalamic nucleus, globus pallidus internus, anterior cingulate cortex, hypothalamus, sphenopalatine ganglion, and occipital nerve. In conclusion, neuromodulation interventions for trigeminal neuralgia is yet to be elucidated; future advancements in this area are required.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.695-701
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• 2003

Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.64-68
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• 2001

Endothelin-1 (ET-1 ), a novel and potent vasoconstrictor in blood vessel, is known to have some functions in the rat central nervous system (CNS), In order to investigate the central functions of ET-1 , ET-1 was administered to the periaqueductal gray area (PAC) of anesthetized rats to induce barrel rolling and increase the arterial blood pressure (ABP). ET-1 had a modulatory effect on central cardiovascular and behavioral control. The selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (3${u}m/ol/kg$, i.p.) blocked the ET-1 induced responses, and both the nitric oxide synthase (NOS) inhibitor L-NAME (N-nitro-L-arginine mIThyl-ester 1 nmol/rat) and the nitric oxide (NO) scavenger hemoglobin (15 nmol/rat) had similar effects in redtAcing the IT-1 (10 pmol/rat)-induced behavioral changes and ABP elevation. However, NO donor sodium nitroprusside (SNP 10${u}g$, 1${u}g/rat$) decreased the ET-1 induced ABP elevation, and recovered the ET-1 -induced barrel rolling effect that was reduced by MK-801. These results suggest that ET-1 might have neuromodulatory functions such as ABP elevation and barrel rolling induction in the PAG of the rats via the NMDA receptor and NO.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.642-650
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• 2006

As an effective non-pharmacological method of pain relief, hydrotherapy was widely used. And bath additive has been used for enhancing the efficacy of hydrotherapy, In the present study, as a bath additive, the analgesic activity of HAC, which composed of Corydalis turtschaninovii, Atractylodes japonica, and Harpagophytum procumbens(HAC), was investigated in the ventrolateral periaqueductal gray (VIPAG), lateral PAG (IPAG), central nuclei of amygdala (CeA), and the paraventricular nucleus of the hypothalamus (PVN) in mice, using writhing test and immunohistochemistry for c-Fos. Male C57BU6 mice weighing $25{\;}{\pm}{\;}2g$ (8 weeks of age) were used for this experiment. The animals were divided into five groups: the control group, the acetic acid treatment group, the acetic acid treatment and 0.01 g/L HAC-immersed group, the acetic acid treatment and 0.1 g/L HAC-immersed group, and the acetic acid treatment and 1.0 g/L HAC-immersed group. To induce somato-visceral pain in the experimental animals, a single intraperitoneal (i.p.) injection of acetic acid was administrated to each animal, and the animals of the control group received injections of equivalent doses of normal saline. The animals of the HAC-immersed groups were immersed the water with HAC powder at the respective doses deep enough to cover the mice body, and those of the control group and the acetic acid treatment group immersed the water without HAC powder at 10 min immediately after the acetic acid injection. Our present study has shown that the HAC reduced the acetic acid-induced abdominal constrictions and the acetic acid-Induced increase of numbers of c-Fos-positive cells in the VIPAG, IPAG, PVN, and CeA. The most potent analgesic effect appeared with the treatment of 1.0 g/L KB-immersed group. Based on our present results, it is very possible that HAC can be a potent therapeutic bath additive for alleviating pain without the fear of addiction to the drugs and side-effects associated with the prescription of multiple analgesic drugs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1483-1490
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• 2007

This study was carried out to investigate the effects of GCP treatment on the expression of NOS, c-fos, serotonin and substance P in central nerve system of monosodium iodoacetate(MIA)-induced osteoarthritic pain model. Arthritis was induced by injection of MIA(0.5 mg) into knee joint cavities of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of GCP by oraly for same duration. Normal group(n=8) was infected with normal saline and was taken distilled water for 20 days. The numbers of NADPH-d positive cells in superficial dorsal horn of spinal cord of treated group($21{\pm}5$) was significantly (p<0.01) decreased compared with control($33{\pm}5$). The numbers of NADPH-d positive cell in dorsolateral periaqueductal gray matter of treated group($111{\pm}16$) was significantly(p<0.01) decreased compared with control($143{\pm}14$). The numbers of c-fos positive cells in dorsal periaqueductal gray matter of treated group($57{\pm}16$) was significantly(p<0.01) decreased compared with control($78{\pm}13$). The numbers of c-fos positive cells in paraventricular thalamic nucleus of treated group($60{\pm}15$) was significantly decreased compared with control($88{\pm}27$). The numbers of serotonin positive cells in median raphe nucleus of treated group($171{\pm}31$) was significantly(p<0.05) decreased compared with control($217{\pm}48$). On the basis of these results, we concluded that GCP treatment has inhibiting effects on the pain transmission in monosodium iodoacetate-induced osteoarthritic pain model in rat.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.113-122
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• 1994

The present study was carried out to characterize the functional properties of spinomesencephalic tract (SMT) neurons in the lumbar spinal cord of urethane anesthetized rats. Extracellular single unit recordings were made from neurons antidromically activated by stimulation of the midbrain area, including the deep layers of superior colliculus, periaqueductal gray and midbrain reticular formation. Recording sites were located in laminae I-VII of spinal cord segments of L2-L5. Receptive field properties and responses to calibrated mechanical stimulation were studied in 78 SMT cells. Mean conduction velocity of SMT neurons was $19.1{\pm}1.04\;m/sec$. SMT units were classified according to their response profiles into four groups: wide dynamic range (58%), deep/tap (23%), high threshold (9%) and low threshold (3%). A simple excitatory receptive field was found for most SMT neurons recorded in superficial dorsal horn (SDH). Large complex inhibitory and/or excitatory receptive fields were found for cells in lateral reticulated area which usually showed long after-discharge. Most of SMT cells received inputs from $A{\delta}$ and C afferent fiber types. These results suggest that sensory neurons in the rat SMT may have different functional roles according to their location in the spinal cord in integrating and processing sensory inputs including noxious mechanical stimuli.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.39-46
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• 2008

Background : Acupuncture has been used as a clinical treatment in Oriental medicine for various diseases including pain relief. The descending pain control system of periaqueductal gray (PAG) is a powerful pain control system in mammalians. Expression of c-Fos is used as a marker for stimuli-induced metabolic changes of neurons. Objective : In the present study, the effects of acupuncture on analgesic effect in visceral pain were investigated through the writhing reflex and c-Fos expression in ventrolateral PAG (vlPAG) area using immunohistochemistry in mice. Method : For the writhing test, mice were divided into five groups. Immediately after finishing the behavioral test, the animals were weighed and overdosed with Zoletil. After a complete lack of response was observed, the brains of the mice were dissected into serial coronal sections, and c-Fos immunohistochemistry was performed. Statistical analysis of all data was performed using one-way ANOVA. Result : The present results showed that acupuncture affected the writhing reflex and that Choksamni (zusnali) acupoint and aspirin significantlysuppressed acetic acid treatment-induced increased writhing reflex, and the expression of c-Fos in vlPAG was significantly increased in the acupunctured group. Conclusion : The present study suggests that acupuncture has an antinociceptive effect on acetic acid-induced visceral pain by increase of c-Fos expression in mice. Aspirin also showed analgesic effect, however the mechanism is different from the acupuncture.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.28-38
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• 2009

Background : Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. Objective : The aim of this study was to evaluate the effects of Gentianae Macrophyllae Radix (G. M. Radix) on the pain control and the recovery of the locomotor function that results from the sciatic crushed nerve injury in rats. Method : Using rats, we crushed their sciatic nerve, and then orally administered the aqueous extract of G. M. Radix. The effects of G. M. Radix on the recovery locomotor function were investigated by walking track analysis. The effects of G. M. Radix on pain control were investigated by brain-derived neurotrophic factor (BDNF) expression in the sciatic nerve, and c-Fos expression in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral periaqueductal gray (vlPAG). Result : G. M. RADIX facilitates motor function from the locomotor deficit, and thereby increased BDNF expression and suppressed painful stimuli in the PVN and vlPAG after sciatic crushed nerve injury. Conclusion : It is suggested that G. M. Radix might aid recovery locomotor function and control pain after sciatic crushed nerve injury. Further studies on identifying specific the component in G.M. Radix associated with enhanced neural activity in the peripheral nerve injury may be helpful to develop therapeutic strategies for the treatment of peripheral nerve injury.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.39-50
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• 2009

Objective : The aim of this study was to evaluate the effects of Aconiti ciliare tuber on the descending pain and the recovery of locomotor function that results from sciatic crushed nerve injury in rats. Method : In order to assess the effects of the aqueous extract of Aconiti ciliare tuber on the recovery rate of locomotor function, we investigated the walking track analysis, and for the effects on the pain control we investigated brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression in the sciatic nerve and on the expressions of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region resulting from the sciatic crushed nerve injury in rats. Result : Treatment with Aconiti ciliare tuber significantly enhanced the SFIvalue, enhanced BDNF expression, decreased iNOS expression, and suppressed c-Fos expression. The present results showed that Aconiti ciliare tuber facilitated functional recovery following sciatic crushed nerve injury in rats. The recovery mechanisms of SFI by Aconiti ciliare tuber might be ascribed to the increase of BDNF expression for nerve regeneration and reinnervation and to the suppression of iNOS expression for inhibiting nerve inflammation. Conclusion : In this process it has been shown that Aconiti ciliare tuber can be used for pain control and functional recovery from peripheral nerve injury.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.66-78
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• 2010

Background: Peripheral nerve injuries are a commonly-encountered clinical problem and often result in a chronic pain and severe functional deficits. Objectives: The aim of this study was to evaluate the effects of acupuncture on the descending pain and the recovery of the locomotor function that follows sciatic crushed nerve injury in rats. Method: In order to assess the effects of acupuncture on the descending pain and functional recovery, we investigated the walking track analysis, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) expression in the sciatic nerve, and on the expressions of c-Fos and nitric oxide synthase in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral periaqueductal gray (vlPAG) region resulting from sciatic crushed nerve injury in rats. Results: Acupuncture treatment at Huantiao (GB30), Yanglingquan (GB34), and Weizhong (BL40) facilitated functional recovery. C-Fos and nitric oxide synthase expressions in the brain and BDNF and TrkB expressions in the sciatic nerve were decreased by acupuncture treatment. The most potent effects of acupuncture were observed at the GB30 acupoint. Conclusion: It is possible that acupuncture can be used for pain control and functional recovery from sciatic nerve injury.