• The Korean Journal of Pain
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• v.14 no.2
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• pp.142-149
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• 2001

Background: The expression of the proto-oncogene c-fos in spinal cord neurons following various noxious stimuli has been demonstrated in numerous studies. However, the pattern of expression of c-fos after incisional stimulus has not been evaluated. This study was designed to examine c-fos expression in an incisional pain model of rats. Methods: A 1 cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hindpaw in enflurane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at areas around the wound before surgery and for the next 48 hours. The expression of c-fos protein in the lumbar spinal cord was examined by immunohistochemistry. Results: After incision, c-fos was strongly expressed within laminae I, II, III, IV, V and VI ipsilateral to the incision. C-fos positive neurons were detected in the controlateral site, as well. Conclusions: These studies suggest that spinal c-fos protein may not be used as a specific marker for spinal nociceptive processing in an incisional pain model.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.143-148
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• 2000

Background: Trigeminovascular system is implicated in the pathophysiology of the headache in migraine. This study was designed to evaluate the pattern of Fos protein expression in trigeminal nociceptive central pathway after meningeal stimulation of rats by capsaicin. Methods: The expression of Fos protein was examined by immunohistochemistry in thalamus, brainstem and upper cervical cord (at three levels corresponding to obex, 0.8 mm and 2 mm below obex) 2 hours after intracisternal injection of either diluted capsaicin solution (0.1 ml, $61{\mu}g/ml$) or normal saline (0.1 ml) through a catheter placed in the cisterna magna, or following epidural instillation of diluted capsaicin solution in urethane-anesthetized Sprague-Dawley rats. Results: Fos immunoreactivity was strongly expressed within lamina I, II of bilateral trigeminal nucleus caudalis (TNC) after cisternal capsaicin injection and magnitude of expression was greatest at level 2.0 mm below obex. Epidural capsaicin caused much less labelling than cisternal capsaicin. Fos positive cells were also observed in area postrema, nucleus of the solitary tract, medullary reticular nucleus and midline nuclear groups of the thalamus with similar intensity between capsaicin and control group. Conclusions: These results indicate that the injection of capsaicin into the cisterna magna is an effective stimulus for the induction of Fos protein within TNC through activation of trigeminovascular afferents and this animal model can be useful for the evaluation of the pathophysiology and drug development in migraine and related headache.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.66-80
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• 2003

Objectives : Recently, herbal acupuncture has been developed in the Korea since the earlier 1960' applied to various diseases including the cerebrovascular accident. The main characteristics of herbal acupuncture are a combination the merit of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. Ramulus Uncariae Cum Uncis (釣鉤藤) has been claimed to possess sedative, anti-spasmodic actions, and treat childhood epilepsy in oriental medical preparation. Also, it has been stated that Ramulus Uncariae Cum Uncis was antioxidatvie effect and neuroprotection against glutamateinduced neuronal death. Methods : In this study, effects of Ramulus Uncariae Cum Uncis' herbal acupuncture on the $GV_{20}{\;}or{\;}LR_3$, named Baek-hue or Tae-chung, on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Results : Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group, respectively. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Especially, cFos expression was more increased at the herbal acupuncture on $GV_{20}{\;}than{\;}LR_3$, but FosB expression was more decreased in $LR_3$ group than $GV_{20}$ group. Also, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($254.88{\pm}12{\;}pg/ml{\;}in{\;}GV_{20}$ group, $245.93{\pm}44.4{\;}pg/ml{\;}in{\;}LR_3$ group) and the cortex ($85.81{\pm}3.45{\;}pg/ml{\;}in{\;}GV_{20}$ group, $111.51{\pm}15.79{\;}pg/ml{\;}in{\;}LR_3$, group) compared to the hippocampus ($134.07{\pm}2.96{\;}pg/ml$) and the cortex ($61.16{\pm}4.11{\;}pg/ml$) in control group at 48 hrs after transient forebrain ischemia. Conclusion : These results suggest that pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $GV_{20}{\;}or{\;}LR_3$ may be related to antioxidative effect and calcium channel block of Ramulus Uncariae Cum Uncis. Also, it could be mentioned there is specificity of acupoints treating ischemic injury through the difference between the herbal acupuncture of $GV_{20}{\;}and{\;}LR_3$.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.367-373
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• 2013

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.47-62
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• 2010

Objectives: Colitis is an inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing events represents. The purpose of this study is to evaluate effects of pharmacopuncture of anti-inflammatory herbal compound (AiC) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods: In Male Sprague - Dawley rats, weighing 250~400g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Acupoints of LI4 (Hapkok), ST25 (Cheonchu), ST36 (Joksamni), and BL25 (Daejangsu) were intramuscularly injected by AiC, respectively (injection volume & times: 0.2 ml / acupoint, twice times on the 2nd & 3rd day). Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hr after TNBS induced colitis by immunohistochemistry. Results: The expression of c-Fos protein in the L6 s.c., Sol, LC and PAG increased 24 hr after TNBS injection into colorectum as compared to normal and 50% ethanol treated group. AiC to LI4 inhibited the expression of c-Fos protein in Sol and PAG but not L6 s.c. and LC. AiC to ST36 showed significant inhibition the c-Fos expression in L6 s.c., Sol and PAG. AiC to ST25 only showed the effects in L6 s.c. and PAG. AiC to BL25 inhibited significantly the expression of c-Fos protein all over the areas. To investigate whether or not endogenous opioids are involved, intrathecal injection of naltrexone (30ug/30ul) was applied before the 2nd pharmacopuncture treatment 24 hr after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem. Conclusions: These data show that pharmacopuncture of Aic potently inhibits signal pathways ascending hypersensitivity of colorectum after TNBS induced colitis and depends on the endogenous opioids according to acupoints.

• Journal of Acupuncture Research
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• v.21 no.1
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• pp.240-251
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• 2004

Objective: We have studied to know effects of acupuncture at SI3, BL40, SI3 BL40 on mechnical allodynia, cold allodynia and c-fos protein expression in a model of neuropathic pain of rat. Methods: A model of neuropathic pain was made by injuring tibial nerve and sural nerve while common peroneal nerve was maintained. after 2 weeks, we performed behavioral tests for 7 days to try out mechnical allodynia using von frey filament and cold allodynia using acetone, which are calculated by counting withdrawal response on foot. Rat brains removed and sliced on 8th days. Serial sections were immunohistochemically reacted with polyclonal c-fos antibody. The numbers of c-Fos protein immunoreactive neurons in the central gray were examined using scion image program. Results: Mechanical allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. Cold allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. c-Fos protein expression on the central gray in the SI3 group were lower than that of the control group. Conclusions: We have noticed that acupuncture at SI3, BL40, SI3 BL40 diminished mechanical allodynia and cold allodynia in a model of neuropathic pain compared with the control group. c- Fos protein expression in the central gray of that group was also decreased compared with the control group. pain control using acupunture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.81-93
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• 2003

Objectives : Recently, the new therapeutic tool, that is herbal acupuncture, has been developed and applied to various diseases including the cerebrovascular accident. The main characteristics of herbal acupuncture are a combination of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. The objective was to determine the effect of folium artemisiae argyi (艾葉) herbal acupuncture on the trasient forebrain ischemic injured rat. Methods : In this study, the effects of folium artemisiae argyi (艾葉) herbal acupuncture on the $LR_3$ named Taechung, on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Results : Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group. These features were observed in the retrosplenial granular cortex as well as the hippocampus. Also, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($263.26{\pm}44.56{\;}pg/ml$ extracted by water, $275.35{\pm}51.47{\;}pg/ml$ extracted by moxa tar)and the cortex ($102.33{\pm}13.65{\;}pg/ml$ extracted by water, $109.54{\pm}9.37{\;}pg/ml$ extracted by moxa tar) compared to the hippocampus ($134.07{\pm}2.96{\;}pg/ml$) and the cortex ($61.16{\pm}4.11{\;}pg/ml$) in control group at 48 hrs after transient forebrain ischemia. Conclusions : These results suggest that pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $LR_3$ may be related to antioxidative function of folium artemisiae argyi.

• Korean Journal of Acupuncture
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• v.20 no.3
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• pp.61-80
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• 2003

Objectives : Acupuncture and herbal medicine have been used to prevent and treat the cerebrovascular accident, such as a stroke, and many studies of acupuncture and moxibustion concerning to the stroke have been undertaken in the human and various animals. Recently, the new therapeutic tool, that is herbal acupuncture, has been developed since the 1950' and applied to various diseases including the cerebrovascular accident. The main characteristics of herbal acupuncture are a combination of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. Methods : In this study, effects of folium Artemisiae Argyi and moxa tar' herbal acupuncture on the $GV_{20}$, named Baek-Hue, on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohis- tochemistry and ELISA technique. Results : Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with folium Artemisiae Argyi or moxa tar' herbal acupuncture on $GV_{20}$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group, respectively. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Also, pretreatment with folium Artemisiae Argyi and moxa tar' herbal acupuncture on$GV_{20}$ significantly increased the expression of BDNF protein in the hippocampus and the cortex compared to control group at 48 hrs after transient forebrain ischemia, respectively. Conclusions : These results suggest that pretreatment with folium Artemisiae Argyi or moxa tar' herbal acupuncture on $GV_{20}$ has neuroprotective effect on transient forebrain ischemia and theherbal acupuncture on $GV_{20}$ may be related to antioxidative function.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.63-81
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• 2005

Herbal acupuncture has been used to prevent and treat the cerebrovascular accident, such as a stroke, and many studies of acupuncture and moxibustion concerning to the stroke have been undertaken in the human and various animals. The main characteristics of herbal acupuncture are a combination of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. In this study, neuroprotective effects of folium artemisiae argyi (艾葉)' herbal acupuncture on the $LR_3$ (Taechung) on the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Also, pretreatment with folium artemisiae argyi' herbal acupuncture on $LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($263.26{\pm}44.56pg/ml$ extracted by water, $275.35{\pm}51.47pg/ml$ extracted by moxa tar)and the cortex ($102.33{\pm}13.65pg/ml$ extracted by water, $109.54{\pm}9.37pg/ml$ extracted by moxa tar) compared to the hippocampus $(134.07{\pm}2.96pg/ml)$ and the cortex $(61.16{\pm}4.11pg/ml)$ in control group at 48 hrs after transient forebrain ischemia. These results suggest that pretreatment with folium artemisiae argyi'herbal acupuncture on $LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $LR_3$ may be related to antioxidative function of folium artemisiae argyi.