• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.31-39
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• 1998

We have investigated the antinociceptive efficacy of ginseng saponins in mice using l% formalin, which induce two phases of pain (acute and tonic pains) and is known to induce a clinically related pain. Ginseng total saponins (GTS) relieved both phases of pain with EDso of 162 mghg for acute and 92 mg/kg for tonic pain, respectively. Both protopanaxadiol (PD) and protopanaxatriol (PT) saponins did not attenuated acute phase of pain but relieved tonic phase of pain with EDso of 45 mg/kg for PD saponins and 105 mghg for PT saponins, respectively. Moreover, ginsenoside Rc, Rd, and Re among representative ginsenosides such as Rbl, Rc, Rd, Re and Rgl relieved slightly but significantly acute phase of pain and strongly attenuated tonic phase of pain but Rf relieved only tonic phase of pain. However, PD and PT saponins, and the individual ginsenosides tested except GTS did not greatly attenuate thermal noxious pain (tail-flick test). These results suggest that single ginsenoside or mixture of various ginsenosides mainly induce differential antinociception in mice.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.99-106
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• 2005

Background: Cyclic guanosine monophosphate (cGMP) and opioid receptors are involved in the modulation of nociception. Although the opioid receptors agonists are active in pain, the effect of an phospodiesterase inhibitor (zaprinast) for increasing the level of cGMP has not been thoroughly investigated at the spinal level. This study examined the effects of intrathecal zaprinast and morphine in a nociceptive test and we also examined the nature of the pharmacological interaction after the coadministration of zaprinast with morphine. The role of the nitric oxide (NO)-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of the drug interaction between zaprinast and morphine. Furthermore, NO synthase inhibitor ($_L-NMMA$), guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide) were intrathecally administered to verify the involvement of the NO-cGMP- potassium channel pathway on the antinociception effect of zaprinast. Results: Both zaprinast and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after the intrathecal administration of the zaprinast-morphine mixture in both phases. Intrathecal $_L-NMMA$, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase. Conclusions: These results suggest that zaprinast, morphine and the mixture of the two drugs are effective against acute pain and they facilitated pain state at the spinal level. Thus, the spinal combination of zaprinast with morphine may be useful for the management of pain. However, the NO-sensitive cGMP-potassium channel pathway did not contribute to the antinocieptive mechanism of zaprinast in the spinal cord.

• The Korean Journal of Pain
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• v.21 no.1
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• pp.27-32
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• 2008

Background: Experimental evidence indicates that ginseng modulate the nociceptive transmission. Authors examined the role of adrenergic and cholinergic receptors on the antinociceptive action of Korean red ginseng against the formalin-induced pain at the spinal level. Methods: Catheters were inserted into the intrathecal space of male Sprague-DawIey rats. Fifty ${\mu}l$ of 5% formalin solution was injected to the hindpaw for induction of pain and formalin-induced pain (flinching response) was observed. The role of spinal adrenergic and cholinergic receptors on the effect of Korean red ginseng was assessed by antagonists (Prazosin, yohimbine, atropine and mecamylamine). Results: Intrathecal Korean red ginseng produced a dose-dependent suppression of the flinching response in the rat formalin test. All of prazosin, yohimbine, atropine and mecamylamine antagonized the antinociception of Korean red ginseng. Conclusions: Spinal Korean red ginseng is effective against acute pain and facilitated pain state evoked by formalin injection. All of alpha 1, alpha 2, muscarinic and nicotinic receptors may play an important role in the antinociceptive action of Korean red ginseng at the spinal level.

• The Korean Journal of Pain
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• v.25 no.4
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• pp.221-227
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• 2012

Background: It has been reported that curcumin, the main active compound of Curcuma longa, also known as turmeric, exhibits antinociceptive properties. The aim of this study was to examine the participation of ATP-sensitive potassium channels ($K_{ATP}$ channels) and, in particular, that of the L-arginine-nitric oxide-cyclic GMP-$K_{ATP}$ channel pathway, in the antinociceptive effect of curcumin. Methods: Pain was induced by the intraplantar injection of 1% formalin in the right hind paw of Wistar rats. Formalin-induced flinching behavior was interpreted as an expression of nociception. The antinociceptive effect of oral curcumin was explored in the presence and absence of local pretreatment with L-NAME, an inhibitor of nitric oxide synthase, ODQ, an inhibitor of soluble guanylyl cyclase, and glibenclamide, a blocker of $K_{ATP}$ channels. Results: Oral curcumin produced a dose-dependent antinociceptive effect in the 1% formalin test. Curcumin-induced antinociception was not altered by local L-NAME or ODQ, but was significantly impaired by glibenclamide. Conclusions: Our results confirm that curcumin is an effective antinociceptive agent. Curcumin-induced antinociception appears to involve the participation of $K_{ATP}$ channels at the peripheral level, as local injection of glibenclamide prevented its effect. Activation of $K_{ATP}$ channels, however, does not occur by activation of the L-arginine-nitric oxide-cGMP-$K_{ATP}$ channel pathway.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.191-197
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• 2016

The present study was to evaluate effects of vitamin E on intravenous administration of lidocaine-induced antinociception. Experiments were carried out using male Sprague-Dawley rats. Orofacial formalin-induced nociceptive behavioral responses were used as the orofacial animal pain model. Subcutaneous injection of formalin produced significant nociceptive scratching behavior. Intraperitoneal injection of 5 and 10 mg/kg of lidocaine attenuated formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. Intraperitoneal injection of 1 g/kg of vitamin E also attenuated the formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. However, low dose of vitamin E (0.5 g/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. The present study also investigated effects of intraperitoneal injection of both vitamin E and lidocaine on orofacial formalin-induced behavioral responses. Vehicle treatment affected neither formalin-induced behavioral responses nor lidocaine-induced antinociceptive effects. However, intraperitoneal injection of 0.5 g/kg of vitamin E enhanced the lidocaine-induced antinociceptive effects in the 2nd phase compared to the vehicle-treated group. Intraperitoneal injection of naloxone, an opioid receptor antagonist, did not affect antinociception produced by intraperitoneal injections of both vitamin E and lidocaine. These results suggest that treatment with vitamin E enhances the systemic treatment with lidocaine-induced antinociception and reduces side effects when systemically treated with lidocaine. Therefore, the combined treatment with vitamin E and lidocaine is a potential therapeutic for chronic orofacial pain.

• CELLMED
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• v.2 no.4
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• pp.38.1-38.6
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• 2012

The present study aimed to determine the possible mechanisms of the peripheral antinociception of the aqueous extracts of Dicranopteris linearis (AEDL), Melastoma malabathricum (AEMM) and Bauhinia purpurea (AEBP) leaves in mice. Briefly, the antinociceptive profile of each extract (300, 500, and 1000 mg/kg; subcutaneous (s.c.)), was established using the abdominal constriction test. A single dose (500 mg/kg) of each extract (s.c.) was pre-challenged for 10 min with various pain receptors' antagonists or pain mediators' blockers and 30 min later subjected to the antinociceptive assay to determine the possible mechanism(s) involved. Based on the results obtained, all extracts exerted significant (p < 0.05) antinociceptive activity with dose-dependent activity observed only with the AEMM. Furthermore, the antinociception of AEDL was attenuated by naloxone, atropine, yohimbine and theophylline; AEMM was reversed by yohimbine, theophylline, thioperamide, pindolol, reserpine, and 4-chloro-DL-phenylalanine methyl ester hydrochloride; and of AEBP was inhibited by naloxone, haloperidol, yohimbine and reserpine. In conclusion, the antinociceptive activity of those extracts possibly involved the activation of several pain receptors (i.e. opioids, muscarinic, ${\alpha}_2$-adrenergic and adenosine receptors, adenosine, H3-histaminergic and $5HT_{1A}$, dopaminergic receptors).

• The Korean Journal of Pain
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• v.19 no.2
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• pp.131-136
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• 2006

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.108-117
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• 2003

Objective : The central opioid mechanism of acupuncture analgesia has been fairly well documented in acute behavioral experiments, but little electrophysiological study has been performed on the peripheral mechanism and subtypes of opioid receptors responsible for acupuncture-induced antinociception in chronic animal models. In the present electrophysiological experiment, we studied the peripheral mechanism and opioid receptor subtypes which Were implicated in electroacupuncture-induced antinociception in the rat with chronic inflammatory and neurogenic pain. Methods : In the rat with complete Freund's adjuvant-induced inflammation and spinal nerve injury, dorsal horn cell responses to afferent C fiber stimulation were recorded before and after electroacupuncture (EA) stimulation applied to the contralateral Zusanli point for 30 minutes. Also studied Were the effects of specific opioid receptor antagonists and naloxone methiodide, which can not cross the blood-brain barrier, on EA-induced inhibitory action. Results : EA-induced inhibitory action was significantly attenuated by naloxone methiodide, suggesting that EA-induced inhibition was mediated through peripheral mechanism. Pretreatment, but not posttreatment of naltrexone and spinal application significantly blocked EA-induced inhibitory actions. In inflammatory and neurogenic pain models, ${\mu}-$ and ${\delta}-opioid$ receptor antagonists (${\beta}-funaltrexamine$ & naltrindole) significantly reduced EA-induced inhibitory action, but ${\kappa}-opioid$ receptor antagonist had weak inhibitory effect on EA-induced antinociception. Conclusion : These results suggest that 2Hz EA-stimulation induced antinoeiceptive action is mediated through peripheral as well as central mechanism, and mainly through ${\mu}-$ and ${\delta}-opioid$ receptors.

• The Korean Journal of Pain
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• v.24 no.4
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• pp.179-184
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• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.209-215
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• 2005

The antinociceptive effect of nicotine administered intracereboventricularly (i.c.v.) or intrathecally (i.t) in several pain models was examined in the present study. We found that i.t. treatment with nicotine (from 5 to 20 g) dose-dependently blocked pain behavior revealed during the second phase, but not during the first phase in the formalin test. In addition, i.c.v. treatment with nicotine (from 0.1 to $10\;{\mu}g$) dose-dependently attenuated pain behavior revealed during both the first and second phases. In addition to the formalin test, nicotine administered i.c.v. or i.t. attenuated acetic acid-induced writhing response. Furthermore, i.c.v. or i.t. administration of nicotine did not cause licking, scratching and biting responses induced by substance P, glutamate, TNF-${\alpha}$(100 pg), IL-$1{\beta}$(100 pg) and INF-${\gamma}$ (100 pg) injectied i.t. The antinociception induced by supraspinally-administered nicotine appears to be more effective than that resulting from spinally administered nicotine. Our results suggest that nicotine administration induces antinociception by acting on the central nervous system and has differing antinociceptive profiles according to the various pain models.