• The Korean Journal of Pain
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• v.32 no.3
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• pp.160-167
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• 2019

Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

• Korean Journal of Pharmacognosy
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• v.18 no.4
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• pp.210-215
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• 1987

Experimental studies were done to investigate analgesic and antiphlogistic actions of Violae Herba. Its water extract showed a significant dose dependent analgesic effect against writhing syndrome induced by acetic acid as well as in hot plate test in mice. The extract also showed a significant inhibitory effect against paw-edema induced by egg-white in rats.

• Natural Product Sciences
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• v.2 no.1
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• pp.24-28
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• 1996

The antiinflammatory and analgesic activities of higenamine were evaluated by measuring edema volume and pain threshold in adjuvant arthritic rats and acetic acid-induced writhing test in mice. Higenamine, with consecutive oral administrations at doses of 10 and 50 mg/kg/day, showed significant antiedemic effect and elevation of pain threshold during the secondary lesion of adjuvant arthritis. Higenamine also showed a significant inhibition of acetic acid-induced writhing syndrome with a single oral administration (200 mg/kg). From these results, it is postulated that higenamine might possess both of centrally and peripherally mediated analgesic properties.

• Korean Journal of Pharmacognosy
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• v.46 no.3
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• pp.229-233
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• 2015

The anti-nociceptive effect of an ethanol extract and its various solvent fractions from Curcuma longa Linne ethanol extract was studied using the writhing test in mice. Different fractions by various solvent extraction from Curcuma longa Linne ethanol extract were administered orally 1 hr or time-course (0.5, 1, 2 and 5 hr) before intraperitoneal injection of acetic acid. After treatment with 30% ethanol extract and n-butanol fraction, CB-1, at a dose of 250 mg/kg, the significant writhing responses were 87.5 ± 13.4 (inhibition rate 31%, p<0.01) and 75.1 ± 11.1 (inhibition rate 41%, p<0.01) lower than the control group. At the dose of CB-1 50 mg/kg and 250 mg/kg, CB-1 showed a similar activity comparing to diclofenac of 10 mg/kg. A time-course experiment was performed, which involved oral administration of CB-1 (250 mg/kg) at 0, 0.5, 1, 2, and 5 hr before acetic acid intraperitoneal injection. The most effective time of CB-1 was 30 min before treatment and persisting until 2 hr. This study showed that Curcuma longa Linne has anti-nociceptive properties comparable with those of diclofenac, which suggests promise for the treatment of intractable visceral pain in humans. Major components of the active fraction are identified as curcumin, cyclocurcumin and demethoxycurcumin.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.143-149
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• 1997

We studied the effects of ginseng protopanaxadiol (PD) and protopanaxatriol (PT) saponins on the analgesia using several pain tests such as writhing, formalin, and tail-flick test. Using mouse, pretreatment of PD or PT saponins (i.p.) induced inhibition of abdominal constrictions caused by 0.9% acetic acid administration(i.p.). The $AD_{50}$ was around 27 (17-43) mg/kg for PD and 13.5 (3-61) mg/kg for PT saponins in writhing test. Both PD and PT saponins also showed the inhibition of bitings and lickings of hindpaw after administration of 1% formalin. In particular, both PD and PT saponins showed analgesic effects on second phase of pain. The $AD_{50}$ was 44.5 (26-76) mg/kg for PD and 105 (55-200) mg/kg for PT saponins in second phase of formalin test. For first phase pain inhibition by PD or PT saponins, they were required higher concentrations. However, PD saponins showed weak analgesic effects in tail-flick test with high concentration. In conclusion, we found that both PD and PT saponins have the analgesic effects in writhing test and second phase of pain in formalin test. These results suggest that both PD and PT saponins inhibit neurogenic or tonic pain rather than acute pain.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.440-446
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• 2022

Background: The authors showed in a previous study that some novel triazine derivatives had an anti-inflammatory effect. The present study was designed to evaluate the antinociceptive effect of five out of nine compounds including two vanillintriazine (5c and 5d) and three phenylpyrazole-triazine (10a, 10b, 10e) derivatives which showed the best anti-inflammatory effect. Methods: Male Swiss mice (25-30 g) were used. To assess the antinociceptive effect, acetic acid-writhing, formalin, and hot plate tests were used after intraperitoneal injection of each compound. Results: All compounds significantly (P < 0.001) reduced acetic acid-induced writhing at tested doses (50, 100, and 200 mg/kg). Also, the percent inhibition of writhing in the acetic acid test showed that at the maximum tested dose of these compounds (200 mg/kg), the order of potencies is as follows: 10b > 10a > 10e > 5d > 5c. In the formalin test, compounds 5d, 10a, and 10e showed an antinociceptive effect in the acute phase and all compounds were effective in the chronic phase. In the hot plate test, compounds 5c, 5d, and 10a demonstrated an antinociceptive effect. Conclusions: The results clearly showed that both vanillin-triazine and phenylpyrazole-triazine derivatives had an antinociceptive effect. Also, some compounds which showed activity in the early phase of formalin test as well as in the hot plate test could control acute pain in addition to chronic or inflammatory pain.

• YAKHAK HOEJI
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• v.55 no.5
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• pp.379-384
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• 2011

The aim of this study was to reduce the side effects and to develop effective drugs using bucillamine (B), lornoxicam (L), and its mixtures on the analgesic and anti-inflammatory effects. With this goal, we compared their effects on the four different mixtures with a sole treatment (B 40 mg/kg and L 1.60 mg/kg). The mixture 1, 2, 3, and 4 ratios of B to L (mg/kg) were 20 to 0.80, 40 to 1.60, 80 to 3.20, and 40 to 1.14, respectively. In terms of acetic acid-induced vascular permeability, B and L inhibited the amount of dye leakage approximately 37.8 and 66.5%, respectively. And mixture 1, 2 and 3 showed inhibition of 47.4%, 81.5%, and 84.3%. The mixture 4 inhibited approximately 49.4%. In carrageenan- induced paw edema model, mixtures of B and L effectively inhibited paw edema measured 1/2~3 hours after carrageenan injection. Especially, mixture 2 inhibited 50.7%, 52.7%, 50.9% of paw edema after 1, 2, and 3 hr, significantly. We also examined an analgesic effect using the writhing test. In terms of the acetic acid-induced writhing syndrome, the control group showed writhing syndrome 18.5 times. B and L showed 9 and 6.3 times, inhibiting 51.6% and 65.9% respectively. And aspirin, as a positive control drug, showed the 7.1 times writhing syndrome. The mixture 1, 2, 3, and 4 also significantly inhibited the writhing syndrome to 62.2%, 93.0%, 51.4%, and 77.8%, respectively. From these results, we could suggest that the range of B and L ratio of 25 : 1 to 35 : 1 may be applicable to developing analgesic and anti-inflammatory drugs.

• The Korean Journal of Pain
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• v.8 no.1
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• pp.25-30
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• 1995

Anlgesic agents against visceral pain typically rely on a noxious chemical irritation of the peritoneum, e. g., acetic acid and phenylquinone writhing test. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints, Colburn et al. developed a model for mechanical visceral pain model (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner. We found that a model for visceral pain was thought to be a great value.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.143-146
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• 2003

Triterpenoids, ursolic acid (1) and 23-hydroxyursolic acid (2) were obtained from the hydrolysis of BuOH fraction of Cussonia bancoensis extract to test anti nociceptive and anti-inflammatory effect of C. bancoensis (Araliaceae). Compound 1 and 2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. The effect of 2 was much more potent in acetic acid-induced writhing test than in hot plate test. Compound 1 and 2 significantly inhibited 1％-carrageenan-induced edema in the rat. These results suggest that the two triterpenes, ursolic acid and 23-hydroxyursolic acid, are responsible for the antinociceptive and anti-inflammatory effect of C. bancoesnsis.

• Bulletin of the Korean Chemical Society
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• v.14 no.2
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• pp.272-274
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• 1993

The alkylated olivetol derivatives were prepared for evaluation as analgesic agents. Olivetol derivatives were proven to have analgesic activity by the acetic acid-induced writhing test and tail-flick test. These compounds were prepared by condensation of appropriate olivetols with cyclic allylic alcohols in the presence of $BF_3$-etherate on alumina.