Yu-Jung Kang

The analgesic effects and mechanisms of orally administered eugenol.

In the present study, the antinociceptive profiles of eugenol were examined in ICR mice. Eugenol administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of eugenol maintained at least for 30 min. Moreover, the cumulative response time of nociceptive behaviors induced by an intraplantar formalin injection was reduced by eugenol treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by eugenol. Intraperitoneal pretreatment with yohimbine (α2-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by eugenol in the writhing test. However, methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by eugenol in the writhing test. Our results suggest that eugenol shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of eugenol may be mediated by α2-adrenergic and opioidergic receptors, but not serotonergic receptor.

The regulation of blood glucose level in physical and emotional stress models: Possible involvement of adrenergic and glucocorticoid systems

This study was done to determine the effect of stress on blood glucose regulation in ICR mice. The stress was induced by the electrical foot shock-witness model. Blood glucose level was found to be increased in the electrical foot shock-induced physical stress group. Furthermore, the blood glucose levels were also elevated in the emotional stress group in both physical and emotional stress groups. The blood glucose level reached maximum 30 min after stress stimulation and returned to normal level 2 h after stress stimulation in both physical and emotional stress groups. Subsequently, we observed that intraperitoneal injection of phentolamine (an α1-adrenergic receptor antagonist), yohimbine (an α2-adrenergic receptor antagonist) or RU486 (a glucocorticoid receptor blocker) significantly inhibited blood glucose level induced by both physical and emotional stress. The results of our study suggest that physical and emotional stress increases blood glucose level via activation of adrenergic and glucocorticoid system.

Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of sympathetic nervous system.

The relationship between interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL-1β increased pain behavior. In addition, i.t. IL-1β injection caused an elevation of the blood glucose level. The time-course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL-1β administration. Furthermore, i.t. injection of IL-1β enhanced the blood glucose level when mice were orally fed with d-glucose. The i.t. administration of IL-1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL-1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL-1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α(1)-adrenergic blocker) or yohimbine (an α(2)-adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β(2)-adrenergic blocker), whereas metoprolol (a β(2)-adrenergic blocker) enhanced IL-1β-induced blood glucose level and pain behavior in mice fed with d-glucose. However, its effect was not statistically significant. Our results suggest that IL-1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system.

Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb 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 µg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by α2-adrenergic receptor, but not opioidergic and serotonergic receptors.

Various pain stimulations cause an increase of the blood glucose level

Abstract The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and pro-inflammatory cytokines (TNF-α and IFN-γ) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-α, and IFN-γ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-α, and IFN-γ caused the elevation of the blood glucose level in d-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the d-glucose-fed group. Our results suggest that the blood glucose level appears to be differentially regulated by various pain stimulation induced by acetic acid, formalin, SP, glutamate, and pro-inflammatory cytokines.

Central anti-diabetic action of biguanide and thizolidinediones in D-glucose fed and streptozotocin-treated mouse models.

BACKGROUND In the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice. METHODS Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.) treated with 20 or 30 μg metformin, pioglitazone and rosiglitazone in d-glucose fed and streptozotocin-treated models, and blood glucose levels was measured at 30, 60 and 120 min after i.c.v. or i.t. administration. RESULTS We found that i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood glucose level in d-glucose fed model, whereas pioglitazone showed no effect on the blood glucose level in d-glucose fed model. The i.t. administration with metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in d-glucose fed model. We also assessed the possible roles of biguanide and thiazolidinedione in the regulation of the blood glucose level in streptozotocin-treated model. We found in the present study that i.c.v. or i.t. administration with metformin caused a pronounced attenuation of the blood glucose level in streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not affect the blood glucose level in streptozotocin-treated model. CONCLUSIONS Our results suggest that the anti-diabetic actions of metformin and rosiglitazone appear to be mediated via the brain regions as revealed in d-glucose fed animal model. Furthermore, metformin administered supraspinally or spinally may be effective for treating type I diabetes mellitus as revealed in streptozotocin-treated mouse model.

Antinociceptive Profiles and Mechanisms of Orally Administered Curcumin in Various Pain Models

Antinociceptive profiles of curcumin in ICR mice were examined. Curcumin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of curcumin was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by curcumin treatment during second phase. Cumulative nociceptive response time for intrathecal injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by curcumin. Intraperitoneal pretreatment with naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist)-attenuated antinociceptive effect induced by curcumin in the writhing test, whereas yohimbine (α2-adrenergic receptor antagonist) did not affect antinociception induced by curcumin, suggesting that curcumin shows antinociceptive property in various pain models, and this antinociceptive effect of curcumin may be mediated by opioidergic and serotonergic receptors, but not α2-adrenergic receptor.

Characterization of blood glucose level regulation in mouse opioid withdrawal models.

The regulation of blood glucose level in intracerebroventricular (i.c.v.) administration with opioid alone or opioid withdrawal model was studied in ICR mice. In the first group, we found that i.c.v. administered morphine or beta-endorphin alone causes an elevation of blood glucose level. Blood glucose level induced by i.c.v. morphine or beta-endorphin began to increase within 30min and reached maximal level at 1h, decreasing to the basal level after 2h. In another group, we observed that intraperitoneal (i.p.) injection with naloxone (10mg/kg) post-treated 3h after either a single i.c.v. injection with morphine or beta-endorphin did not affect the increased blood glucose level in either group. In the next study, we observed that multiple (1 time/day for 3 days) i.c.v. injection with morphine alone significantly increased the blood glucose level. However, i.p. injection with naloxone post-treated 3h after the last i.c.v. injection with morphine caused a decrease of blood glucose level. We found that multiple (1 time/day for 3 days) i.c.v. injections with beta-endorphin did not affect the blood glucose level. Furthermore, i.p. injection with naloxone did not affect the blood glucose level in the mice injected with multiply beta-endorphin. Our results suggest that both morphine and beta-endorphin administered i.c.v. acutely increases the blood glucose level. However, blood glucose levels in the groups of multiply administered morphine alone, beta-endorphin alone, and naloxone-treated withdrawal model in multiply injected morphine and beta-endorphin appear to be differentially regulated.

Hop Extract Produces Antinociception by Acting on Opioid System in Mice

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 µg) or glutamate (20 µg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α2-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and α2-adrenergic receptors.

The differential profiles of withdrawal symptoms induced by morphine and beta-endorphin administered intracerebroventricularly in mice

In the present study, withdrawal symptoms induced by morphine or β-endorphin administered intracerebroventricularly (i.c.v.) were compared in ICR mice. Naloxone (10mg/kg) was post-treated intraperitoneally (i.p.) 3h after either a single or repeated (1 time/day for 3 days) i.c.v. injections with opioids. Withdrawal symptoms such as jumping frequency, diarrhea, weight loss, rearing, penile licking and paw tremor were observed for 30 min immediately after naloxone treatment. Withdrawal symptoms (jumping, diarrhea, weight loss, rearing, penile licking and paw tremor) observed in the group treated with morphine was persistently increased during 3 days. On the other hand, withdrawal symptoms such as diarrhea, weight loss and rearing in β-endorphin-treated group were increased after a single injection with β-endorphin, but gradually decreased after the repeated injection. Furthermore, no jumping behavior, penile licking and paw tremor in β-endorphin-treated group were observed throughout the whole period of time. In addition, the hypothalamic changes of several signal molecules such as pERK, pCaMK-IIα, c-FOS and pCREB expression were observed during the presence or absence of withdrawal responses induced by morphine or β-endorphin administered once or repeatedly. Both hypothalamic pCaMK-IIα and c-FOS expressions were increased by naloxone treatment in acutely administered morphine group, whereas only pCaMK-IIα expression was elevated by naloxone treatment in repeatedly administered morphine group. In contrast with the findings in morphine-treated group, only pCaMK-IIα expression was decreased by naloxone treatment in repeatedly administered β-endorphin group. Our results suggest that profiles of the withdrawal symptoms induced by morphine and β-endorphin administered supraspinally appear to be differentially regulated. The pCaMK-IIα and the c-FOS protein expression may play important roles for the regulation of naloxone-precipitated withdrawal symptoms such as jumping, diarrhea, weight loss, rearing, penile licking and paw tremor induced by morphine-treated group, whereas the phosphorylation of hypothalamic pCaMK-IIα appears to be involved only in the regulation of naloxone-precipitated withdrawal symptoms such as diarrhea, weight loss and rearing in β-endorphin-treated group.