• The Korean Journal of Physiology
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• v.30 no.1
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• pp.97-104
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• 1996

Different neural substrates have been reported to be implicated in analgesic mechanisms in the acute phasic and the sustained tonic pains. To explore the differential antinociceptive action of diphenylhydantoin (DPH) and carbamazepine (CBZ) on the acute phasic and the tonic pains, changes in tail flick latency, hot plate latency and the formalin-induced nociceptive score were assessed prior to and after intraperitoneal administration of DPH (20 & 40 mg/Kg) and CBZ (20 mg/Kg). In 11 rats, CBZ was administered repeatedly for 6 days at the dose of 20 mg/Kg/day. Also studied were the effects of strychnine and picrotoxin (1 mg/Kg, i.p.) on the CBZ-produced changes in the formalin-induced pain behaviors. The tail flick and hot plate ltencies were not changes after administration of DPH and CBZ. However DPH strongly suppressed the formalin-induced tonic pain. A single and the repeated administration of CBZ inhibited both the early phasic and the late tonic pain responses to formalin in n similar manner. On the other hand, the antinociceptive actions of CBZ were not altered by strychnine or picrotoxin. These experimental findings lead to the conclusion that DPH and CBZ have differential antinociceptive action on the acute and the tonic pains and that their antinociceptive actions are independent of the GABA- and glycine-receptors.

• Journal of Ginseng Research
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• v.27 no.3
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• pp.120-128
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• 2003

Alternative medicines such as herbal products are increasingly being used for preventive and therapeutic purposes. Ginseng is the best known and most popular herbal medicine used worldwide. In spite of some beneficial effects of ginseng on the nervous system, little scientific evidence shows at the cellular level. In the present study, I have examined the direct modulation of ginseng total saponins and individual ginsenosides on the activation of $Ca^{2+}$ channels and NMDA-gated channels in cultured rat dorsal root ganglion (DRG) and hippocampal neurons, respectively. In DRG neurons, application of ginseng total saponins suppressed high-voltage-activated $Ca^{2+}$ channel currents and ginsenoside Rg$_3$, among the 11 ginsenosides tested, produced the strongest inhibition on $Ca^{2+}$ channel currents. Occlusion experiments using selective $Ca^{2+}$ channel blockers revealed that ginsenoside Rg$_3$ could modulate L-, N-, and P/Q-type currents. In addition, ginsenoside Rg$_3$ also proved to be an active component of ginseng actions on NMDA receptors in cultured hippocampal neurons. Application of ginsenoside Rg$_3$ suppressed NMDA-induced [Ca$^{2+}$]$_{i}$ increase and -gated channels using fura-2-based digital imaging and patch-clamp techniques, respectively. These results suggest that the modulation of $Ca^{2+}$ channels and NMDA receptors by ginsenoside Rg$_3$ could be part of the pharmacological basis of ginseng actions in the peripheral and central nervous systems.ous systems.

• Journal of Acupuncture Research
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• v.23 no.4
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• pp.149-162
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• 2006

Objectives : The aim of this study is to evaluate the analgesic effect of electroacupuncture on Jogsamni (ST36) in the collagen-induced arthritis rats and investigate the role played by opioid receptor subtypes $({\mu},\;{\delta},\;{\kappa})$ in the antinociceptive effect of electroacupuncture (EA) In the thermal hyper algesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type H collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 2 weeks later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization, EA stimulation (2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni (5736) for 20 minutes. Analgesic effect was evaluated by using the tail flick latency (TFL) after intraperitoneal injection of normal saline, naloxone, naltrindole and nor-binaltorphimine respectively to CIA rats. Results : The results were as follows; 1. The TFL were gradually decreased in CIA as time elapsed after e immunization of arthrogenic collagen and the maximum value was reached between the third to fifth week. 2. EA stimulation on 5736 inhibited chronic inflammatory pain induced by CIA. 3. The analgesic effect of EA was inhibited by pretreatment of ${\mu}-receptor$ antagonist (naloxone),${\delta}-receptor$ antagonist (naltrindole) and ${\kappa}-receptor$ antagonist (nor-binaltorphimine) respectively. Conclusion : Electroacupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by 8, 5, H receptors.

• The Korean Journal of Pain
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• v.23 no.3
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• pp.179-185
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• 2010

Background: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats. Methods: Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated. Results: Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle. Conclusions: Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

• The Korean Journal of Pain
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• v.22 no.3
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• pp.206-209
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• 2009

Background: The essential oil of Ocimum basilicum (EOOB) has a pleasant aroma and is known to have antimicrobial and insecticidal activities. In addition, it is used as a pain reliever in folk medicine. However, there are few reports on the antinociceptive activities of EOOB. Methods: This study examined the antinociceptive effects of EOOB using formalin and a plantar test in mice. In the formalin test, EOOB (50 mg/kg, 100 mg/kg, 150 mg/kg) was administered intraperitoneally and the licking time of the mice was measured. In the plantar test, intraperitoneal EOOB (50 mg/kg, 100 mg/kg) was administered and the withdrawal latency was measured using the Hargreaves method. Results: In the formalin test, EOOB (50 mg/kg, IP) showed significant decreases in licking time in the second phase. On the other hand, in the plantar test, there were no significant effects in any of the groups examined. Conclusions: These results support the traditional use of EOOB for the treatment of painful conditions. However, there is a need for more research to determine the active chemical constituents and the precise mechanism.

• The Korean Journal of Pain
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• v.22 no.3
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• pp.199-205
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• 2009

Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.

• The Korean Journal of Pain
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• v.24 no.3
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• pp.131-136
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• 2011

Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.121-125
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• 2013

The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.