• 한국약용작물학회지
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• 제18권4호
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• pp.238-243
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• 2010

In the present study, the antinociceptive profiles of Viola tricolor L. (V. tricolor L.) extract were examined in ICR mice. V. tricolor L. extract administered orally (200mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, V. tricolor L. extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by V. tricolor L. extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by V. tricolor L. extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by V. tricolor L. extract in the writhing test. Our results suggest that V. tricolor L. extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of V. tricolor L. extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• 대한본초학회지
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• 제25권3호
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• pp.97-101
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• 2010

Objectives : The present study investigated the anti-nociceptive and anti-inflammatory properties of the water extract of Geranii Herba (The stem and leaves of Geranium thunbergii Sieb. et Zucc.) in the animal models of pain and inflammation. Methods : We evaluated the anti-nociceptive and anti-inflammatory activities of Geranii Herba extract (GHE) using the writhing test, tail-flick test, carrageenan-induced paw edema and xylene-induced ear edema models. Two dose of GHE (100 and 1000 mg/kg) was administrated orally to the mice. Control group received normal saline and ibuprofen (50 mg/kg) was used as a positive control drug. Results : GHE 1000 mg/kg treated group showed an increased tail-flick response time in the tail-flick test and inhibitory effect on writhing syndrome induced by acetic acid. Treatment with GHE at the same dose inhibited ear edema induced by xylene and foot edema induced by carrageenan toxicity. Conclusion : The results demonstrate that GHE has anti-nociceptive and anti-inflammatory effects in the various models of nociception and inflammation.

• The Korean Journal of Pain
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• 제13권2호
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• pp.175-181
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• 2000

Background: Pain is often measured using psychophysical scaling techniques. However, all of these methods found their limits, since they were based on the subjective sensations reported by the subjects. It is, therefore, desirable to validate psychophysical pain measures by simultaneously measuring some physiological correlate of nociception. We studied an objective method for measuring pain in human volunteer using R(III) nociceptive flexion reflex. Methods: Four different intensity of electrical stimuli between perception and 1.4 times the R(III) nociceptive flexion threshold were delivered to the sole of the feet in 8 normal volunteers. We measured the flexion reflex activity in the skin over the ipsilateral tibialis anterior muscle and subjects rated each stimulus on a visual analog scale (VAS) Results: Both R(III) nociceptive flexion reflex activity and VAS ratings showed a linear relationship with stimulus intensity and with each other in all volunteers. Conclusions: R(III) nociceptive flexion reflex elicited through electrical stimulation may used as an objective pain measurement, previsionary based on our study paradigm.

• Advances in Traditional Medicine
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• 제8권2호
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• pp.196-203
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• 2008

The methanol extract of the root of Artanema sesamoides Family Scrophuilariaceae (MEAS) was investigated for possible analgesic and anti-inflammatory effects in animals. Three models were used to study the extract effects on nociception, which were acetic acid-induced writhing response, hot-plate method and the tail flick test in mice. The antiinflammatory effects were evaluated using carrageenan, dextran, histamine and serotonin induced rat paw oedema (acute) and cotton pellet induced granuloma (chronic) models in rats. Results of the study revealed that the extract exhibited significant (P < 0.001) analgesic effect at a dose of 50, 100 and 200 mg/kg b.w p.o in mice in all the models. In acute model, the MEAS also exhibited significant (P < 0.001) antiinflammatory effect in all the above mentioned doses. In chronic model (cotton pellet induced granuloma) the MEAS 200 mg/kg and indomethacin 10 mg/kg showed that inhibition of granuloma formation 25.0% and 47.7% respectively (P < 0.001). The MEAS and indomethacin were effectively preventing the transudation of the fluid. Thus, the present study revealed that the methanol extract of the root of Artanema sesamoides exhibited significant analgesic and antiinflammatory activity.

• The Korean Journal of Pain
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• 제18권2호
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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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• 제19권1호
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• pp.17-21
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• 2006

Background: Cyclic guanosine monophosphate (cGMP) plays an important role in the modulation of nociception. Although local sildenafil produces antinociception, by increasing cGMP through the inhibition of phosphodiesterase 5, the effect of spinal sildenafil has not been determined. The authors evaluated the effects of intrathecal sildenafil on the nociceptive behavior evoked by formalin injection and thermal stimulation. Methods: Lumbar intrathecal catheters were implanted into rats, with formalin and Hot-Box tests used as nociceptive models. The formalin-induced nociceptive behavior (flinching response) and withdrawal latency to radiant heat were measured, and the general behaviors also observed. Results: The intrathecal administration of sildenafil produced dose-dependent suppression of the flinches in both phases in the formalin test, and increased the withdrawal latency in the Hot-Box test. No abnormal behaviors were noted. Conclusions: Sildenafil, an inhibitor of phosphodiesterase 5, is active against the nociceptive state evoked in the spinal cord by formalin and thermal stimulations. Accordingly, spinal sildenafil may be useful in the management of pain.

• The Korean Journal of Pain
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• 제22권3호
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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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• 제25권4호
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• pp.238-244
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• 2012

Background: Vitamin E is widely known to be one of the reactive oxygen species (ROS) scavengers and a drug that can easily be obtained, and it has been shown to attenuate the pain responses induced by various causes in animal pain models. Thus, this experiment was conducted to assess the antinociceptive effects of vitamin E by comparing intraperitoneal and intrathecal injections in rats subjected to the formalin test. Methods: After the intraperitoneal and intrathecal injections of vitamin E were carried out, respectively (IP: 500 mg/kg, 1 g/kg, and 2 g/kg, IT: 3 mg/kg, 10 mg/kg, and 30 mg/kg), the formalin test was perfumed. As soon as 5% formalin was injected into left hind paw, the number of flinches induced by pain was measured at 5-minute intervals for 1 hour. Results: Formalin injected into the left hind paw induced biphasic nociceptive behavior in all animals. Intraperitoneal injection of vitamin E diminished the nociceptive behavior in a dose-dependent manner during the early and late phase. Intrathecal vitamin E diminished nociceptive behavior dose dependently during the late phase but showed no significant difference in the early phase. Conclusions: Vitamin E attenuated acute nociception when it was injected systemically, while both systemic and intrathecal injection produced analgesia in a rat model of formalin-induced hyperalgesia.

• The Korean Journal of Pain
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• 제25권4호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.275-281
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• 2000

Cholecystokinin (CCK) is a gastrointestinal hormone which plays an important role in satiety and gastric motility. It is also widely distributed throughout the central nervous system, where it appears to be involved in the central control of anxiety, feeding behavior and nociception. Two distinct CCK receptor types, $CCK_A$ and $CCK_B,$ have been found in the brain. Both CCK receptors coexist in the rat nucleus tractus solitarius (NTS), which is the primary center for the coordination of peripheral and central activities related to gastrointestinal, cardiovascular and respiratory functions. In order to study ionic actions of CCK on each type of receptor, we investigated the effects of CCK-8S on neurons located in the NTS of the rat using whole-cell patch-clamp recordings in brainstem slices. Application of CCK-8S, under current clamp, produced a membrane depolarization accompanied by action potential firing. This CCK-evoked excitation was dose-dependent $(10\;nM{\sim}10\;{\mu}M)$ and observed in more than 60% of NTS neurons. Under voltage clamp conditions, CCK-8S induced an inward current with a notably increased spontaneous excitatory synaptic activity. However, CCK-8S did not significantly change the amplitude of pharmacologically isolated and evoked EPSP(C)s. Using selective $CCK_A$ and $CCK_B$ receptor antagonists, we observed two different effects of CCK-8S, which suggest $CCK_A$ receptor-mediated inhibitory and $CCK_B$ receptor-mediated excitatory effects in the NTS. These results may help to explain the ability of CCK to modulate gastrointestinal and other reflex systems in the NTS.