• Archives of Pharmacal Research
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• v.16 no.3
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• pp.237-243
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• 1993

These studies were performed to investigate the acting sites of ginseng total saponins (GTS) on the U-50, 488H-induced antinociception and the inhibitory effect of the development of tolerance to U-50, 488H-induced antinociception by GTS were studied. The U-50, 488H-induced antinociception was ntagonized in mice pretreated with GTS intraperitoneally, intracerebrally. These antagonisms were reversed by the pretratment iwth a serotonin precursor, 5-hydroxytrypophan (5-HTP), but not with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA). However, the intraplantar sites. On the other hand, GTS inhibited the development of tolerance to U-50, 488H-induced antinociception was reversed by pretreatment with 5-HTP, but not with L-DOPA. Therefore, the antagonism of U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception by GTS are dependent on serotonegic mechanisms.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.109-114
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• 1997

The effect of total saponin fraction of Ginseng injected intrathecally (i.1.) or in- tracerebroventricularly (i.c.v.) on the antinociception induced by D-$Pen^{2,5}$- enkephalin (DPDPE) ad ministered i.c.v. was studied in ICR mice in the present study. The antinociception was assessed by the tail-flick test. Total saponin fraction at doses 0.1 to 1.0 $\mu\textrm{g}$, which administered i.t. Alone did not affect the latencies of tail-flick threshold, attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered DPDPE (10 $\mu\textrm{g}$). However, total saponin fraction at doses 1 to 20 $\mu\textrm{g}$, which administered i.c.v. Alone did not affect the latencies of the tail-flick response, did not affect i.c.v. administered DPDPE (10 $\mu\textrm{g}$)-induced antinociception. The duration of antagonistic action of total saponin fraction against DPDPE-induced antlnociception was lasted at least for 6 hrs. Various doses of ginsenosides Rd, but not $\Rb_2$, Rc, Rg1, and $\Rb_1$ and Re, injected i.t. Dose-dependently attenuated antinociception induced by DPDPE administered i.c.v. Our results indicate that total saponin fraction injected spinally appears to have antagonistic action against the antinociception induced by supraspinally applied DPDPE. Ginsenoside Rd appears to be responsible for blocking j.c.v. administered DPDPE-induced antinociception. On the other hand, total ginseng fraction, at supraspinal sites, may not have an antagonistic action against the antinociception induced by DPDPE.

• International Journal of Oral Biology
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• v.34 no.3
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• pp.137-142
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• 2009

Whole-body $\gamma$-irradiation(WBI), which produces an oxidative stress, is reported to attenuate the acute antinociceptive action of morphine (a $\mu$-opioid receptor agonist), but not DPLPE (a $\delta$-opioid receptor agonist), in mice. Recently, we also reported that antinociceptive effect of morphine, but not $\beta$-endorphin (a novel $\varepsilon$-opioid receptor agonist), was attenuated by oxidative stress. These findings prompted us to investigate the effect of WBI on the antinociception of morphine and $\beta$-endorphin in mice. Mice were exposed to WBI (5 Gy) from a $^{60}Co$ gamma-source and tested 2 hours later for antinociception produced by intracerebroventricular administration of morphine or $\beta$-endorphin using the hot water tail-immersion and the writhing tests. WBI significantly attenuated the antinociception produced by morphine only in the hot water tail-immersion test, whereas the antinociception of $\beta$-endorphin was significantly potentiated by WBI in both tests. These results demonstrate a differential sensitivity of $\mu$- and $\varepsilon$-opioid receptors to WBI, and support the hypothesis that morphine and $\beta$-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.

• Journal of Ginseng Research
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• v.19 no.3
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• pp.202-205
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• 1995

We have previously reported that the antagonism of U-50,488H-induced antinociception in mice pretreated with ginseng total saponins (GTS) Ivas abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not by a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA) in the tail flick test. In the present experiments, the effect of the same GTS on the development of tolerance to U-50,488H-induced antinociception was determined. GTS inhibited the development of tolerance to U-50,488H-induced antinociception. The inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception was reversed by 5-HTP, but not by L-DOPA. These findings suggest that the inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception is dependent on serotonergic mechanisms. Key words Ginseng total saponin, U-50,488H, tolerance, serotonin.

• Journal of Ginseng Research
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• v.22 no.1
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• pp.43-50
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• 1998

We demonstrated in previous study that protopanaxadiol and protopanxatriol saponins show antinociceptive activity in acetic acid induced writhing test and in the second phase (11-40 min) of formalin test but not tail-flick test. To identify further which ginsenoside has antinociceptive activity among various ginseng saponins, we have investigated antinociceptive effects of several ginsenosides using writhing and formalin test. Ginsenoside Rc, Rd, Re, and Rf induced antinociception in writhing test. These four ginsenosides also induced antinociception in the second phase of formalin (11-40 min) test but these ginsenosides showed a slight antinociception in the first phase (010 min) of formalin test except ginsenoside Rf. The antinociceptive effects induced by the ginsenosides were dose dependent and were not blocked by an opioid receptor antagonist, naloxone. The order of antinociceptive potency was Rd > Rc > Re > Rf in the formalin test. However, these ginsenosides did not show any significant analgesic effects in a tail-flick test. These results suggest that ginsenosides such as Rc, Rd, Re, and Rf inhibit tonic pain rather than acute pain induced by noxious heat. These results also indicate that the antinociceptive activity. Induced by ginsenosides may be one of the actions for pharmacological effects of Panax ginseng.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.17-26
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• 1995

The present studies were carried out to determine if antinociceptive action of morphine and ${\beta}-endorphin$ administered intraventricularly was changed in. pentobarbital anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Antinociception was assessed by the tail-flick test. The $ED_{50}$ values of antinociception for morphine administered intraventricularly were 1.9 and 1.2 nmol for WKY and SHR rats, respectively. The $ED_{50}$ values of antinociception for ${\beta}-endorphin$ administered intraventricularly were 0.40 and 0.12 nmol for WKY and SHR rats, respectively. The $[Met^5]-enkephalin$ (ME) and proenkephalin mRNA levels in midbrain, pons and medulla, or lumbar section of the spinal cord in WKY and SHR rats were measured by the radioimmunoassay and Northern blot assay, respectively. There were no differences of ME and proenkephalin mRNA levels in these tissues between WKY and SHR rats. The results suggest that ${\beta}-endorphin$ but not morphine administered intraventricularly produces a greater antinociception in SHR rats. This increased antinociceptive effect of ${\beta}-endorphin$ in SHR rats may be not, at least, due to the alterations of ME And proenkephalin mRNA levels in the midbrain, pons and medulla, or spinal cord.

• The Korean Journal of Pain
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• v.11 no.1
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• pp.1-6
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• 1998

Background: The role of nitric oxide(NO) in analgesia from opioids is controversial. On the one hand, IV morphine analgesia is enhanced by IV injection of NO synthase inhibitors. On the other hand, IV morphine results in increased release of NO in the spinal cord. There have been no behavioral studies examining the interaction between IV morphine and intrathecal injection of drugs which affect NO synthesis. Method: Rats were prepared with chronic lumbar intrathecal catheters and were tested withdrawal latency on the hot plate after 3~5 days of surgery. Antinociception was determinined in response to a heat stimulus to the hind paw before and after IV injection of morphine, 2.5 mg/kg. Twenty minutes after morphine injection, rats received intrathecal injection of saline or the NO synthase inhibitors, L-NMMA or TRIM, the NO scavenger, PTIO, or the NO synthase substrate, L-Arginine. Intrathecal injections, separated by 15 min, were made in each rats and measurements were obtained every 5 min. Result: Mophine produced a 60~70% maximal antinociceptive response to a heat stimulus in all animals for 60 min in control experiments. Intrathecal injection of idazoxane decreased antinociception of IV morphine. The NO synthase inhibitors and the NO scavenger produced dose-dependent decreases in antinociceptive effect of morphine, whereas saline as a control group and L-Arginine as the NO substrate had no effect on antinociception of morphine. Conclusion: The present study supports the evidences that systemic morphine increase the nitrite in cerebrospinal fluid and dorsal horn. These data suggest that the synthesis of NO in the spinal cord may be important to the analgesic effect of IV morphine and increased NO in spinal cord has different action from the supraspinal NO.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.186-195
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• 2006

The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.

• The Korean Journal of Pain
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• v.23 no.4
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• pp.236-241
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• 2010

Background: Selective inhibitors of cycloosygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antionociception of selective COX-2 inhibitor. Methods: To examine the antionociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are ${\mu}$, $\delta$, and k opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2 Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test, CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1, Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The $\delta$ and $\kappa$ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the ${\mu}$ opioid receptor is related only to facilitated pain.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.54-57
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• 1995

The effect of Ruthenium Red on the antinociceptive action of capsaicinoids was investigated using tail-flick test in mice. Capsaicin and KR-25018, when administered subcutaneously, had a potent antinociceptive effect against noxious heat stimulus. Ruthenium Red which is known to block the calcium channel coupled to the capsaicin receptor, when injected intraperitoneally more than 5 mg/kg, showed severe sedation and apparent antinociceptive effect against noxious heat stimulus. The 2.5 mg/kg Ruthenium Red, at which dose any significant sedative effect was not shown, had no effect on the antinociceptive effects of capsaicin and KR-25018. Considering this result, the antinociceptive effect of capsaicinoid may not be related to the Ruthenium Red sensitive calcium channel which is activated by capsaicin.