Application of the psychology of working theory with Korean emerging adults.

Psychology of Working Theory (PWT; Duffy, Blustein, Diemer, & Autin, 2016) is a recently developed framework aimed at documenting predictors and outcomes of decent work. To date, no studies have explored the applicability of the psychology of working perspective with emerging adults. The goal of the present study is to examine the predictor portion of PWT with a sample of Korean emerging adults from diverse economic backgrounds. Data were collected from a sample of 407 emerging adults attending a large junior college in Korea. Overall, most of the hypothesized direct paths were significant, with economic resources positively relating to both work volition and career adaptability and these positively relating to occupational engagement and future perceptions of securing decent work. Support for the hypothesized indirect effects was mixed. Overall, results suggest that the PWT is generally relevant and applicable to emerging adults when population-appropriate outcomes are included in the model and that the theory is supported in the Korean context. Based on the results, we also propose that interventions based on malleable psychological factors-the mediators in our study-may be targets when working with emerging adults experiencing economic constraints. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

Immunohistochemical Localization of Calbindin D28k, Parvalbumin, and Calretinin in the Superior Olivary Complex of Circling Mice.

The circling mouse serves as a hearing loss model. It has spontaneous tmie gene mutations that cause hair cell and cochlear degeneration. However, little is known about the role of the tmie gene in superior olivary complex (SOC) regions, in which sound information from the two ears is integrated and primarily relayed to the nuclei of the lateral lemniscus and inferior colliculus. Several studies have reported that abnormal calcium (Ca2+) homeostasis is associated with the pathology of hearing loss. This study investigated the distribution of Ca2+-binding proteins (CaBPs), such as calbindin D28k, parvalbumin, and calretinin, in the SOC of the circling mouse on postnatal day 16. A comparison of wild-type (+/+), heterozygous (+/cir), and homozygous (cir/cir) mice showed that CaBP immunoreactivity was significantly decreased in the auditory nucleus of the SOC of homozygous (cir/cir) mice. A decline in the CaBPs level in the SOC may be the result of hearing loss through hair cell and cochlear degeneration following tmie gene mutation.

Methyl gallate from Acer barbinerve decreases melanin synthesis in Mel-Ab cells.

Methyl gallate (MG) was isolated from the bark of Acer barbinerve, which has traditionally been used in Oriental medicine. In the present study, we examined the effects of MG on melanin synthesis in Mel-Ab melanocyte cells. MG decreased melanin pigmentation in a concentration-dependent manner, but did not directly inhibit tyrosinase activity. Further analysis showed that MG had no effect on extracellular signal-regulated kinase (ERK) activation, but induced phosphorylation of glycogen synthase kinase (GSK)3ß, which is known to increase ß-catenin accumulation. Accordingly, the ß-catenin level was increased by MG. However, a specific GSK3ß inhibitor did not rescue the MG-induced inhibition of melanogenesis. Additionally, MG decreased the protein expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, which regulate melanin synthesis. Based on these results, we conclude that MG inhibits melanogenesis by decreasing the expression of MITF and tyrosinase.

Pertussis toxin administered spinally induces a hypoglycemic effect on normal and diabetic mice.

BACKGROUND/AIMS: To show whether intrathecal (i.t.) treatment with pertussis toxin (PTX) produces a hypoglycemic effect in ICR, db/db and streptozotocin-treated mice. METHODS: The blood glucose level (BGL) was measured after i.t. treatment with PTX, AB5 toxins and PTX subunits. Insulin or leptin levels were measured after PTX injection. The effect of PTX on the BGL was examined in adrenalectomized (ADX) mice. Glucose transporter (GLUT) levels were determined by Western blotting. RESULTS: PTX attenuated the elevated BGL in the D-glucose-fed model in a long-term manner. Heat-labile toxin (HLT), HLT subunit B or Shiga toxin, which belong to the AB5 toxins, administered i.t. did not affect the BGL. PTX A protomer (PTX-A) or PTX B oligomers (PTX-B) injected i.t. did not have an effect on the BGL as well. However, combined treatment with PTX-A and PTX-B subunits caused a hypoglycemic effect. The leptin level was gradually reduced by PTX for up to 6 days, without affecting the insulin level. PTX administered i.t. significantly decreased the BGL further in ADX mice. Moreover, GLUT-2 (hypothalamus and pituitary gland), GLUT-4 (muscle) and GLUT-3 (adrenal gland) expression levels were increased, whereas GLUT-1 (brain cortex, liver, muscle and spinal cord), GLUT-2 (liver) and GLUT-3 (brain cortex and pituitary gland) expression levels were decreased. DISCUSSION: Our data suggest that PTX administered spinally produces a hypoglycemic effect in a long-term manner, and PTX-induced hypoglycemia appears to be mediated by the reduction in activity of the glucocorticoid system. Furthermore, PTX may modulate the insulin level during hypoglycemia. Among GLUTs, GLUT-4 in muscle, GLUT-2 in the liver, hypothalamus and pituitary gland as well as GLUT-1 in the adrenal gland may be responsible for PTX-induced hypoglycemia.

Alteration of striatal tetrahydrobiopterin in iron-induced unilateral model of Parkinson's disease.

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin (BH4) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of BH4 into neuron would induce the neuronal toxicity in vitro. To elucidate a role of BH4 in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and BH4 at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and BH4 levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of BH4 was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of BH4 in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both BH4 and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of BH4 can deteriorate the disease progression in early phase of PD, and the inhibition of BH4 increase could be a strategy for PD treatment.

Deficiency of alpha-calcitonin gene-related peptide induces inflammatory responses and lethality in sepsis.

In the present study, we examined the role of alpha-calcitonin gene-related peptide (αCGRP) on expression of neuropeptides in the brain, inflammatory responses, and survival rate in septic shock condition. We examined expression of neuropeptides such as αCGRP, proopiomelanocortin (POMC), corticotrophin releasing hormone (CRH), and proenkephalin (ProENK) in the hippocampus and hypothalamus in C57BL/6 (WT) or αCGRP-/- (KO) mice subjected to sepsis. Cecal ligation and puncture (CLP) or lipopolysaccharide/D-galactosamine (LPS/D-GalN) treatment showed significant increases of hippocampal and hypothalamic αCGRP, POMC, CRH, and ProENK mRNA levels in WT mice, but not ProENK mRNA in the hypothalamus at 6h after on-set of sepsis. However, enhanced mRNA levels of POMC, CRH, and ProENK genes were not increased in the hippocampus and hypothalamus of CLP-subjected KO mice at 6h following sepsis. KO mice treated with LPS/D-GalN displayed a significant enhancement of plasma corticosterone, aspartate aminotransferase, and alanine aminotransferase levels compared to LPS/D-GalN treated WT mice at 12h after induction of sepsis. In addition, plasma levels of pro-inflammatory cytokines, such as IL-1ß and TNF-α, were also further increased in KO mice compared to WT mice at 24h after CLP or LPS/D-GalN treatment. Interestingly, mRNA expressions of IL-6 and IL-10, anti-inflammatory cytokines, were synergistically enhanced in liver and lymph node of KO mice compared to WT mice at 6h after CLP. However, plasma level of IL-10 but not IL-6 was significantly decreased in KO mice compared to WT mice at 24h after CLP or LPS/D-GalN challenge. The survival rate of KO mice was significantly reduced compared to WT mice following mild (1 punch) and moderate (2 punch) CLP and LPS/D-GalN administration. Taken together, our findings suggest that the activation of αCGRP may induce other neuropeptides associated with immunomodulation at CNS level and modulate immune responses as enhancing anti-inflammatory cytokines and reducing pro-inflammatory cytokines during the sepsis.

Anti-Depressant Like Effect of Methyl Gallate Isolated from Acer barbinerve in Mice.

In the present study, the anti-depressant like effect of methyl gallate (MG) isolated from the stem bark of Acer barbinerve was examined in ICR mice. Body weight (BDW) and blood glucose (BDG) levels significantly decreased in the repeated restraint stress (RRS) group (2 h/day for 14 days) compared to the no stress (NS) group. To examine the effect of MG on RS-induced BDW loss and hypoglycemia, MG (10 mg/kg) and the anti-depressant fluoxetine (10 mg/kg) were administered daily for 14 days. Orally administered MG and fluoxetine significantly attenuated the RS-induced BDW loss and hypoglycemia. Interestingly, MG administered mice showed increased BDG levels in the normal and glucose feeding condition. Chronic RS-subjected mice showed immobilized and depressed behaviors. The effect of MG on the depressed behaviors was evaluated using the tail-suspension test (TST) and the forced swimming test (FST). In both tests, RS-induced immobilized behaviors were significantly reversed in MG and fluoxetine administered groups. Taken together, MG significantly attenuated the RS-induced BDW loss, hypoglycemia, and depressed behaviors. Considering that decreased BDG levels (hypoglycemia) can cause depression, MG may exert its anti-depressant like effect by preventing hypoglycemia. Our results suggest that MG isolated from A. barbinerve can exert anti-depressant like effect, and could be used as a new and natural anti-depressant therapy.

Differential Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on Motor Behavior and Dopamine Levels at Brain Regions in Three Different Mouse Strains.

Developing an animal model for a specific disease is very important in the understanding of the underlying mechanism of the disease and allows testing of newly developed new drugs before human application. However, which of the plethora of experimental animal species to use in model development can be perplexing. Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a very well known method to induce the symptoms of Parkinson's disease in mice. But, there is very limited information about the different sensitivities to MPTP among mouse strains. Here, we tested three different mouse strains (C57BL/6, Balb-C, and ICR) as a Parkinsonian model by repeated MPTP injections. In addition to behavioral analysis, endogenous levels of dopamine and tetrahydrobiopterin in mice brain regions, such as striatum, substantia nigra, and hippocampus were directly quantified by liquid chromatography-tandem mass spectrometry. Repeated administrations of MPTP significantly affected the moving distances and rearing frequencies in all three mouse strains. The endogenous dopamine concentrations and expression levels of tyrosine hydroxylase were significantly decreased after the repeated injections, but tetrahydrobiopterin did not change in analyzed brain regions. However, susceptibilities of the mice to MPTP were differed based on the degree of behavioral change, dopamine concentration in brain regions, and expression levels of tyrosine hydroxylase, with C57BL/6 and Balb-C mice being more sensitive to the dopaminergic neuronal toxicity of MPTP than ICR mice.

Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice.

BACKGROUND: Botulinum neurotoxin type A (BoNT/A) has been used as an analgesic for myofascial pain syndromes, migraine, and other types of headaches. Although an antinociceptive effect of central or peripheral administration of BoNT/A is suggested, the effect at the spinal level is still unclear. In this study, we evaluated the antinociceptive effect of intrathecally administered BoNT/A on the ICR mice during the formalin test. METHODS: BoNT/A (0.01 U/mouse) was injected intrathecally in ICR mice, and we observed formalin-induced inflammatory pain behaviors at days 1, 4, 7, 10, 14, 21, and 28 after the injection. We also examined the level of calcitonin gene-related peptide (CGRP), phosphorylated extracellullar signal-regulated kinases (p-ERK), and phosphorylated Ca(2+)/calmodulin-dependent protein kinase type 2 (p-CaMK-II) using immunoblot or immunohistochemical analyses before and after BoNT/A intrathecal injection. RESULTS: Even a single intrathecal injection of BoNT/A significantly decreased the nociceptive responses in the first phase (10 and 14 days later) and in the second phase of the formalin test at 1, 4, 7, 10, and 14 days later (P < 0.05) without any locomotor changes. Interestingly, intrathecal BoNT/A attenuated the expression level of CGRP, p-ERK, and p-CaMK-II in the 4th and 5th lumbar spinal dorsal horn at 10 days after injection in comparison with control. CONCLUSIONS: We showed that intrathecally administered BoNT/A may have a central analgesic effect on inflammatory pain through the modulation of central sensitization. BoNT/A, with its long-lasting antinociceptive effect, may be a useful analgesic in inflammatory pain.

The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice.

BACKGROUND: The possible role of dopamine D2 receptors located in the spinal cord in the regulation of the blood glucose level have not been investigated before. METHODS: In the present study, the effect of D2 receptor agonist and antagonist administered intrathecal (it) injection on the blood glucose level were examined in the Institute of Cancer Research (ICR) mice. RESULTS: We found that it injection with carmoxirole (D2 receptor agonist) caused an elevation of the blood glucose level in a dose-dependent manner. Carmoxirole-induced increase of the blood glucose was significantly attenuated by L-741,626 (D2 receptor antagonist). Previously, we indicated that intrathecal (it) treatment with 0.1 µg/5 µl pertussis toxin (PTX, a Gi/Go inhibitor) produces a hypoglycemic effect in ICR in a long-term manner. In the present study, it pretreatment with PTX for 6 days almost abolished the hyperglycemic effect induced by carmoxirole. The plasma insulin level was elevated by carmoxirole, and L-741,626 or PTX pretreatment reduced carmoxirole-induced increment of the insulin level. In addition, the plasma corticosterone level was increased by carmoxirole but it pretreatment with L-741,626 or PTX did not affect carmoxirole-induced increment of the corticosterone level. CONCLUSION: Our results suggest that D2 receptors located in the spinal cord play an important role in the elevation of the blood glucose level. Spinally located inhibitory G-proteins appear to be involved in hyperglycemic effect induced by carmoxirole.

Antinociceptive profiles and mechanisms of orally administered vanillin in the mice.

In the present study, the antinociceptive profiles of vanillin were examined in ICR mice. Vanillin 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 vanillin maintained at least for 30 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 microg) or glutamate (20 microg) injection was not affected by vanillin. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by vanillin in the writhing test. However, phentolamine (alpha1-adrenergic receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by vanillin in the writhing test. Our results suggest that vanillin exerts a selective antinociceptive property in the acetic acid-induced visceral inflammatory pain model. Furthermore, this antinociceptive effect of vanillin may be mediated by alpha2-adrenergic and opioid receptors, but not alpha1-adrenergic and serotonergic receptors.

The analgesic effect of decursinol.

Although decursinol, which is one of the coumarins purified from the dried roots of Angelica gigas Nakai, was previously demonstrated to have antinociceptive effects on various mouse pain models such as tail-flick, hot-plate, formalin, writhing, and several cytokine-induced pain tests, the possible involvement of its analgesic effects and non-steroidal anti-inflammatory drugs (NSAIDs) has not been clearly elucidated yet. In this study, we characterized the possible interaction between decursinol and aspirin or acetaminophen in the writhing test. The antinociceptive effects of decursinol were observed at an orally-administered dose of 50 mg/kg but not at 25 or 10 mg/kg. In addition, the analgesic effects of aspirin (ASA) and acetaminophen (APAP) were shown at an orally-administered dose of 200 mg/kg but not at 50 or 100 mg/kg. We examined the effects of decursinol on the ASA or APAP at sub-analgesic doses. Although the co-administration of decursinol and ASA did not show any differences at doses of 10 or 25 mg/kg and 50 or 100 mg/kg, respectively, synergistic effects between decursinol and APAP were observed in the group of decursinol (25 mg/kg) and APAP (100 mg/kg) co-administration. These results indicated that the analgesic effect of decursinol might be involved in supraspinal cyclooxygenase regulation that might be overlapped with APAP-induced analgesic mechanisms rather than systemic or peripheral prostaglandin modulation.

Possible Effects of Radiofrequency Electromagnetic Field Exposure on Central Nerve System.

Technological advances of mankind, through the development of electrical and communication technologies, have resulted in the exposure to artificial electromagnetic fields (EMF). Technological growth is expected to continue; as such, the amount of EMF exposure will continue to increase steadily. In particular, the use-time of smart phones, that have become a necessity for modern people, is steadily increasing. Social concerns and interest in the impact on the cranial nervous system are increased when considering the area where the mobile phone is used. However, before discussing possible effects of radiofrequency-electromagnetic field (RF-EMF) on the human body, several factors must be investigated about the influence of EMFs at the level of research using in vitro or animal models. Scientific studies on the mechanism of biological effects are also required. It has been found that RF-EMF can induce changes in central nervous system nerve cells, including neuronal cell apoptosis, changes in the function of the nerve myelin and ion channels; furthermore, RF-EMF act as a stress source in living creatures. The possible biological effects of RF-EMF exposure have not yet been proven, and there are insufficient data on biological hazards to provide a clear answer to possible health risks. Therefore, it is necessary to study the biological response to RF-EMF in consideration of the comprehensive exposure with regard to the use of various devices by individuals. In this review, we summarize the possible biological effects of RF-EMF exposure.

The differential effect of morphine and beta-endorphin administered intracerebroventricularly on pERK and pCaMK-II expression induced by various nociceptive stimuli in mice brains.

The present study was performed to characterize the differential molecular mechanisms of morphine and beta-endorphin which are injected intracerebroventiricularly in mice. In the immunoblot assay, the increases of phosphorylated extracellular signal-regulated protein kinase (pERK) as well as phosphorylated calcium/calmodulin-dependent protein kinase IIalpha (pCaMK-IIalpha) expression induced by noxious stimuli were attenuated by intracerebroventricular (i.c.v.) beta-endorphin pretreatment in the hypothalamus, but not by i.c.v. morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIalpha immunoreactivity elicited by i.c.v. pretreatment of beta-endorphin mainly occurred in the paraventricular nucleus of the hypothalamus (PVN). We also investigated the effect of morphine and beta-endorphin on pERK and pCaMK-IIalpha expression in the locus coeruleus (LC). I.c.v. injection of morphine significantly increased pERK as well as pCaMK-IIalpha expression in the locus coeruleus, while beta-endorphin increased only pCaMK-IIalpha in the LC. In addition, beta-endorphin significantly attenuated pERK expression induced by SP i.t. injection. These results suggest that the antinociceptive effects of supraspinally administered morphine and beta-endorphin are involved with differentially intracellular signal transduction molecules-pERK, pCaMK-IIalpha in the PVN and the LC.

The differential effects of emotional or physical stress on pain behaviors or on c-Fos immunoreactivity in paraventricular nucleus or arcuate nucleus.

Although many studies which explore on the interaction between stress and antinociception have been conducted, most of them do not divide stress into emotional stress (ES) and physical stress (PS). In the present study, we investigated the differential effects of ES or PS on pain behaviors or on c-Fos immunoreactivity (IR) in the paraventricular nucleus (PVN) or arcuate nucleus (ArcN) using electrical footshock-witness model. In addition, alteration of pain behaviors or c-Fos IR following stress repetition was examined. The electrical foot shock was applied to PS animal group in one chamber, whereas the witness animal group in another chamber without any electrical foot shock was regarded as an ES. In each group, either single (10 stimuli /10 min/1 day) or repeated stress for 5 consecutive days was applied. Our results suggest that ES and PS appear to play differential roles in the regulation of nociception produced by various types of pain stimuli (formalin, substance P, glutamate or pro-inflammatory cytokines) and on c-Fos IR in the PVN or ArcN. Moreover, such antinociceptive effect or c-Fos IR appears to be modified following stress repetition.

Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death.

Statins are inhibitors of HMG-CoA reductase that have been recently recognized as anti-inflammatory and neuroprotective drugs. Herein, we investigated anti-excitotoxic and anti-seizure effects of statins by using kainic acid (KA)-rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. We observed that pre-treatment with Lipitor (atorvastatin) efficiently reduced KA-induced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In addition, we also observed that lovastatin treatment attenuated KA- or glutamate-induced excitotoxicity of cultured hippocampal neurons. These observations suggest a potential for use of statin treatment in modulation of seizures and other neurological diseases associated with excitotoxicity.

The repeated immobilization stress increases IL-1beta immunoreactivities in only neuron, but not astrocyte or microglia in hippocampal CA1 region, striatum and paraventricular nucleus.

The effect of repeated immobilization stress (RIS) on the expression of interleukin-1beta (IL-1beta) and types of cells that express IL-1beta in hippocampal CA1 region, striatum and paraventricular nucleus (PVN) were investigated in ICR mice. The RIS was induced daily for 2h for 4 consecutive days. In the immunohistochemical study, RIS increased IL-1beta immunoreactivities (IR) in the hippocampal CA1 region and striatum and PVN. The RIS also increased glial fibrillary acidic protein (GFAP) IR and complement receptor type 3 (OX-42) IR in the hippocampal CA1 regions and striatum but not PVN. In confocal immunofluorescence study, the IL-1beta IR increased by RIS were colocalized with only NeuN, but not GFAP or OX-42 in the hippocampal CA1 region, striatum and PVN. Our results indicate that RIS increases IL-1beta IR on neuron, but not astrocyte or microglia in the hippocampal CA1 region, striatum and PVN, suggesting that the IL-1beta IR on neuron may play an important role during RIS. In addition, GFAP and OX-42 increased by RIS may be involved indirectly in playing another role in the hippocampal CA1 region and striatum during RIS.

The differential effects of acetaminophen on lipopolysaccharide induced hyperalgesia in various mouse pain models.

We investigated effects of acetaminophen on LPS-induced hyperalgesia in various pain models. We examined the changes of pain behaviors induced by formalin injected subcutaneously (s.c.) in the hind paw, with substance P (SP) and glutamate injected inthrathecally (i.t.). Hyperalgesia was induced by LPS intraperitoneal injection 1 day prior to the pain test. LPS-induced hyperalgesia was exhibited in nociceptive behaviors induced by formalin s.c. (only in the second phase), SP and glutamate i.t. injection. APAP showed a dose-dependent antinociceptive effect on the saline- and LPS-pretreated group in the formalin and SP pain model. However, the analgesic effect of APAP was not observed in the glutamate pain model. To clarify the action site, APAP was administered i.t. or intracerebroventricularly (i.c.v.) 30 min prior to behavioral tests. The 2nd phase of formalin response was not only increased by LPS, but it also significantly attenuated by i.c.v. injections of APAP. However, the effect of APAP was observed only in the LPS-pretreatment, but not in the control group. These results suggest that LPS-induced hyperalgesia in the formalin 2nd phase may be involved in the SP-sensitive neuronal pathways, in which the hyperalgesic response elicited by LPS attenuated by APAP with supraspinal pain modulatory mechanisms.

Intracerebroventricular ginsenosides are antinociceptive in proinflammatory cytokine-induced pain behaviors of mice.

Several ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg3) are neuroprotective and antinociceptive agents. In this study, we assessed the effects of these ginsenosides following intracerebroventricular (i.c.v.) administration on the nociceptive behaviors induced by intrathecal injection of pro-inflammatory cytokines (tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma)). The ginsenosides, Rb1, Rb2, Rc, Rd, Re, Rf and Rg1, significantly attenuated the nociceptive behavior induced by TNF-alpha, IL-1 beta, and IFN-gamma injection, but ginsenoside-Rg3 did not. These results suggest that several ginsenosides may regulate the nociceptive processing induced by pro-inflammatory cytokines.