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An interesting van der Waals material, Ta2NiSe5 has been known one of strong excitonic insulator candidates since it has very small or zero bandgap and can have a strong exciton binding energy because of its quasi-one-dimensional crystal structure. Here we investigate a single crystal Ta2NiSe5 using optical spectroscopy. Ta2NiSe5 has quasi-one-dimensional chains along the a-axis. We have obtained anisotropic optical properties of a single crystal Ta2NiSe5 along the a- and c-axes. The measured a- and c-axis optical conductivities exhibit large anisotropic electronic and phononic properties. With regard to the a-axis optical conductivity, a sharp peak near 3050 cm−1 at 9 K, with a well-defined optical gap ($${{\boldsymbol{\Delta }}}_{{\boldsymbol{o}}{\boldsymbol{p}}}^{{\boldsymbol{E}}{\boldsymbol{I}}}\,{\boldsymbol{\simeq }}$$ΔopEI≃ 1800 cm−1) and a strong temperature-dependence, is observed. With an increase in temperature, this peak broadens and the optical energy gap closes around ∼325 K ($${{\boldsymbol{T}}}_{{\boldsymbol{c}}}^{{\boldsymbol{E}}{\boldsymbol{I}}}$$TcEI). The spectral weight redistribution with respect to the frequency and temperature indicates that the normalized optical energy gap $$({{\boldsymbol{\Delta }}}_{{\boldsymbol{o}}{\boldsymbol{p}}}^{{\boldsymbol{E}}{\boldsymbol{I}}}({\boldsymbol{T}})/\,{{\boldsymbol{\Delta }}}_{{\boldsymbol{o}}{\boldsymbol{p}}}^{{\boldsymbol{E}}{\boldsymbol{I}}}{\bf{(0)}})$$(ΔopEI(T)/ΔopEI(0)) is $${\bf{1}}{\boldsymbol{-}}{({\boldsymbol{T}}/{{\boldsymbol{T}}}_{{\boldsymbol{c}}}^{{\boldsymbol{E}}{\boldsymbol{I}}})}^{{\bf{2}}}$$1−(T/TcEI)2. The temperature-dependent superfluid plasma frequency of the excitonic condensation in Ta2NiSe5 has been determined from measured optical data. Our study may pave new avenues in the future research on excitonic insulators.

Introduction Non-small-cell lung cancer (NSCLC) is one of the most common cancers and the leading cause of cancer-related deaths. In East Asia, traditional herbal medicine (THM) is commonly used in clinical settings for the treatment of cancer. Therefore, the aim of the present review was to systematically assess the efficacy of THM with varied components for the treatment of NSCLC. Methods This study identified randomized controlled trials (RCTs) that evaluated the effectiveness of combined THM and chemotherapy (CTx) in searches of English, Chinese, Japanese, and Korean language databases. Results This meta-analysis systematically reviewed 27 RCTs involving 2382 patients and found that THM improved the quality of life (QoL) significantly for patients with NSCLC. Improvement in QoL was seen in 19 studies using the Karnofsky Performance Status score, three studies using the Eastern Cooperative Oncology Group scale, three studies using the Functional Assessment of Cancer Therapy-Lung scale, and six studies using the European Organization for Research and Treatment of Cancer. Conclusions The pooled results of this systematic review and meta-analysis suggest that THM significantly improved the QoL for patients with NSCLC.

Summary Objectives To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs). Methods Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. Results Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of quality of life (QOL) compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed. Conclusion THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QOL and in decreasing the number of hot flashes per day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues.

Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α₁-adrenergic receptor antagonists, 10 μg); however, idazoxan (α₂-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α₁-adrenergic receptors.

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprisingCinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma,andAconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.

Background. Acupuncture has been shown to reduce preoperative anxiety in several previous randomized controlled trials (RCTs). In order to assess the preoperative anxiolytic efficacy of acupuncture therapy, this study conducted a meta-analysis of an array of appropriate studies.Methods. Four electronic databases (MEDLINE, EMBASE, CENTRAL, and CINAHL) were searched up to February 2014. In the meta-analysis data were included from RCT studies in which groups receiving preoperative acupuncture treatment were compared with control groups receiving a placebo for anxiety.Results. Fourteen publications (N= 1,034) were included. Six publications, using the State-Trait Anxiety Inventory-State (STAI-S), reported that acupuncture interventions led to greater reductions in preoperative anxiety relative to sham acupuncture (mean difference = 5.63,P< .00001, 95% CI [4.14, 7.11]). Further eight publications, employing visual analogue scales (VAS), also indicated significant differences in preoperative anxiety amelioration between acupuncture and sham acupuncture (mean difference = 19.23,P< .00001, 95% CI [16.34, 22.12]).Conclusions. Acupuncture therapy aiming at reducing preoperative anxiety has a statistically significant effect relative to placebo or nontreatment conditions. Well-designed and rigorous studies that employ large sample sizes are necessary to corroborate this finding.

The present study investigated the antiobesity effect ofAchyranthes bidentataBlume root water extract in a 3T3-L1 adipocyte differentiation model and rats fed with a high-fat diet. To investigate the effect ofAchyranthes bidentataBlume on adipogenesisin vitro, differentiating 3T3-L1 cells in adipocyte-induction media were treated every two days withAchyranthes bidentataBlume at various concentrations (1 to 25 μg/mL) for eight days. We found thatAchyranthes bidentataBlume root inhibited 3T3-L1 adipocyte differentiation without affecting cell viability, and Western blot analysis revealed that phospho-Akt expression was markedly decreased, whereas there was no significant change in perilipin expression. Furthermore, administration ofAchyranthes bidentataBlume root (0.5 g/kg body weight for six weeks) to rats fed with a high-fat diet significantly reduced body weight gain without affecting food intake, and the level of triglyceride was significantly decreased when compared to those in rats fed with only a high-fat diet. These results suggest thatAchyranthes bidentataBlume root water extract could have a beneficial effect on inhibition of adipogenesis and controlling body weight in rats fed with a high-fat diet.

Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

Objective. To assess the effectiveness of acupuncture as complementary therapy for gouty arthritis from randomized controlled trials (RCTs). Methods. Five electronic databases, including English and Chinese, were systematically searched until August 2012. All RCTs involving acupuncture in combination with conventional therapy for gouty arthritis were included. Results. Ten RCTs involving 852 gouty arthritis patients were systematically reviewed. Among them six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no significant decrease in uric acid in the treatment group compared with the control group. The remaining four studies of 380 patients reported a significant decrease in visual analogue scale score in the treatment group. Conclusion. The results of the studies included here suggest that acupuncture is efficacious as complementary therapy for gouty arthritis patients. More research and well-designed, rigorous and large clinical trials are necessary to address these issues.

Objective We investigated the reasons and rates of attrition in knee osteoarthritis trials through a systematic review of randomized, placebo-controlled, clinical trials. Methods Randomized trials were identified by searches conducted in MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled Trials. We then attempted to identify and describe the reasons for attrition and their associated themes. For each theme, we calculated the rate of patients who discontinued a trial from the total number of dropouts in each trial. The rates obtained with different trials were combined using a random effects model. We also performed a random effects meta-regression analysis to identify sources associated with the rates. Results Overall, 259 studies consisting of 266 trials and 13,593 patients were included in the analysis. From these, we short-listed 54 attrition reasons and identified 21 key themes. “Ineffectiveness” and “adverse event” were the reasons frequently reported by >5% of the dropouts. On further investigation of the theme ineffectiveness, the attrition rate was associated with delivery routes of treatment, trial duration, flare design, prohibition of usual analgesics, and allowing the use of escape medication. In cases of adverse events, we found that the treatment type and delivery route affected the attrition rate. Conclusions Our findings not only support the importance of the intention-to-treat analysis, but also suggest the possibility of controlling the attrition at the study level.

Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4+ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.

Knee osteoarthritis is the most common form of joint disease and is a major cause of pain and physical disability among the elderly. Although, numerous treatments have been developed to treat osteoarthritis, no definitive treatments with high efficacy and low risk have been identified until now. In recent years, it has been reported that nutraceuticals may be good candidates for the management of knee osteoarthritis. This paper describes the efficacy of nutraceuticals for treating knee osteoarthritis in terms of pain and structural change. To accomplish this, this paper reports on the analysis of randomized, placebo-controlled, clinical trials that were published prior to December 2011. Key words : Nutraceuticals, knee, osteoarthritis, pain.

Summary Objectives We investigated the relationship between the placebo effect and the trial or patient characteristics. Data sources We identified randomized clinical trials with acupuncture, sham and no-treatment groups in which no-treatment or conventional therapy was applied to the no-treatment group. Thirty-one trials in which no treatment was applied in the no-treatment group were categorised as ‘strict' trials. Thirty-nine trials in which no-treatment or conventional therapy was applied to the no-treatment group were categorised as ‘less strict' trials. We calculated the treatment effect, defined as the difference in the effect size between the acupuncture and no-treatment groups, and the placebo effect, defined as the difference in the effect size between the sham and no-treatment groups. Then, a random effect meta-regression analysis was performed on the two effects with respect to trial or patient characteristics. Results The treatment effect was not found to be associated with any factors in both the strict and less strict trials. However, the placebo effect was found to be associated with the publication year in both the strict and less strict trials ( P =0.009 and 0.005, respectively). The placebo effect increased by 0.05 in effect size per year in trials that were published more recently. Conclusion While the treatment effect was not influenced by any trial or patient characteristics, the placebo effect was associated with the publication year.

Neuropathic pain remains one of the most difficult clinical pain syndromes to treat. It is traditionally viewed as being mediated solely by neurons; however, glial cells have recently been implicated as powerful modulators of pain. It is known that the analgesic effects of electroacupuncture (EA) are mediated by descending pain inhibitory systems, which mainly involve spinal opioid, adrenergic, dopaminergic, serotonergic, and cholinergic receptors. However, studies investigating the suppressive effects of EA on spinal glial activation are rare. In the present study, we assessed the cumulative analgesic effects of EA on mechanical and warm allodynia in a rat model of neuropathic pain. We investigated the clinical efficacy of EA as long-term therapy and examined its effects on spinal glia, matrix metalloproteinase (MMP)-9/MMP-2, proinflammatory cytokines and serum immunoglobulin G (IgG) concentration. Rats were randomly divided into four groups as follows: the operation group (OP), operation with EA-non acupoint (EA-NA), operation with EA-ST36 acupoint (EA-ST36), and sham operation (shamOP). Following neuropathic or sham surgery, repeated EA was performed every other day after the behavioral test. On day 53 after the behavioral test, rats were perfused for immunohistochemistry and Western blot analysis to observe quantitative changes in spinal glial markers such as OX-42, astrocytic glial fibrillary acidic protein (GFAP), MMP-9/MMP-2, and proinflammatory cytokines. Allodynia and OX-42/GFAP/MMP-9/MMP-2/tumor necrosis factor (TNF)-α/interleukin (IL)-1β activity in the EA-ST36 group was significantly reduced, compared to the OP and EA-NA groups, and IgG in EA-ST36 rats significantly increased. Our results suggest that the analgesic effect of EA may be partly mediated via inhibition of inflammation and glial activation and repeated EA stimulation may be useful for treating chronic pain clinically.

Ethnopharmacological relevance: Atractylodes macrocephala Koidzumi (AMK) is an herbal medicine traditionally used for treatment of abdominal pain, gastrointestinal disease, obesity, and related complications. Aim of the study: We investigated the effects and molecular mechanism of AMK rhizome water extract on 3T3-L1 adipogenesis and an animal model of obesity. Materials and methods To study the effect of AMK on adipogenesis in vitro , differentiating 3T3-L1 cells were treated every two days with AMK at various concentrations (1–25 μg/ml) for eight days. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the inhibitory mechanism of AMK on adipogenesis, phosphorylation levels of Akt and expression of perilipin, were analyzed by Western blotting. AMK was administered orally to high fat diet (HFD)-induced obese rats to confirm its effect in vivo . Results AMK inhibited 3T3-L1 adipocyte differentiation in a dose-dependent manner without cellular toxicity. Phospho-Akt expression was highly decreased by AMK treatment, whereas there was no significant change in perilipin expression. AMK administration significantly reduced the body weight of rats fed a HFD. Plasma triglyceride levels were significantly lower in the AMK -treated HFD group than those in the HFD control group or normal diet (ND) group, although serum total, HDL- and LDL-cholesterol levels did not differ between the groups. Conclusion These results demonstrate an inhibitory effect of AMK on adipogenesis through reduction of an adipogenic factor, phospho-Akt. AMK had a beneficial effect, reducing body weight gain in a HFD-induced animal model of obesity.

Clinical evidence indicates that electroacupuncture (EA) is effective for allergic disorder. Recent animal studies have shown that EA treatment reduces levels of IgE and Th2 cytokines in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). The hypothalamus, a brain center of the neural-immune system, is known to be activated by EA stimulation. This study was performed to identify and characterize the differentially expressed genes in the hypothalamus of DNP-KLH immunized mice that were stimulated with EA or only restrained. To this aim, we conducted a microarray analysis to evaluate the global gene expression profiles, using the hypothalamic RNA samples taken from three groups of mice: (i) normal control group (no treatments); (ii) IMH group (DNP-KLH immunization + restraint); and (iii) IMEA group (immunization + EA stimulation). The microarray analysis revealed that total 39 genes were altered in their expression levels by EA treatment. Ten genes, including T-cell receptor alpha variable region family 13 subfamily 1 (Tcra-V13.1), heat shock protein 1B (Hspa1b) and 2′–5′oligoadenylate synthetase 1F (Oas1f), were up-regulated in the IMEA group when compared with the IMH group. In contrast, 29 genes, including decay accelerating factor 2 (Daf2), NAD(P)H dehydrogenase, quinone 1 (Nqo1) and programmed cell death 1 ligand 2 (Pdcd1lg2) were down-regulated in the IMEA group as compared with the IMH group. These results suggest that EA treatment can modulate immune response in DNP-KLH immunized mice by regulating expression levels of genes that are associated with innate immune, cellular defense and/or other kinds of immune system in the hypothalamus.

Cholecystokinin, a satiety hormone, acts on cholecystokinin A receptor on vagal afferent neurons that project to the nucleus tractus solitarius, resulting in inhibition of feeding. Cholecystokinin is known to be released by electroacupuncture stimulation at certain body sites which elicits profound psychophysiological responses. Our previous study has revealed the involvement of cholecystokinin and cholecystokinin A receptor in the electroacupuncture stimulation-induced modulation of feeding. The aim of the present study was to examine whether electroacupuncture stimulation at the acupuncture point ST36 (Joksamni) activates the nucleus tractus solitarius neurons and whether such effect is mediated by cholecystokinin A receptor.Using an immunofluorescent analysis of Fos, a neuronal activation marker, we compared the Fos immunoreactivity of the nucleus tractus solitarius among three groups of Sprague-Dawley rats: (1) control (48 hour fasting + saline pre-treatment + no electroacupuncture stimulation); (2) SalEA (48 hour fasting + saline pre-treatment + ST36 electroacupuncture stimulation); (3) LorEA (48 hour fasting + pre-treatment of cholecystokinin A receptor antagonist, lorglumide + ST36 electroacupuncture stimulation).ST36 electroacupuncture stimulation significantly reduced 30 minute food intake (p0.05, SalEA versus control) and increased Fos expression in the nucleus tractus solitarius (p0.01, SalEA versus control). The effects of electroacupuncture on food intake and Fos were blocked by a lorglumide pre-treatment (p0.05, LorEA versus control).Our finding suggests that ST36 electroacupuncture stimulation activates the nucleus tractus solitarius neurons via cholecystokinin A receptor signaling pathway, which may be the underlying central mechanism of electroacupuncture-induced satiety effect.

The primary aim of this study was to assess the effectiveness of possible interventions for hemiplegic shoulder pain. The secondary aim was to investigate whether reduction of subluxation or spasticity can decrease shoulder pain and whether a change in shoulder pain is related to change in passive shoulder external rotation.MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials databases were searched to obtain the randomised, controlled trials. Two authors independently extracted data and assessed the methodological quality of studies.Eight randomised trials were found in electronic databases. Aromatherapy plus acupressure, slow-stroke back massage and intramuscular neuromuscular electric stimulation were more effective than the controls at the end of treatment sessions. Intramuscular botulinum neurotoxin A injection and intraarticular triamcinolone acetonide injection were not helpful at one or three months after the end of treatment. Only intramuscular electric stimulation was effective at three months. These analyses found that shoulder pain improved independently of spasticity and subluxation. It was confirmed that the change in shoulder pain was associated with change in passive shoulder external rotation.Although five interventions were used for managing hemiplegic shoulder pain, their effects were limited in the context of trials.

Inulin, a naturally occurring, functional food ingredient found in various edible plants, has been reported to exert potential health benefits, including decreased risk of colonic diseases, non–insulin-dependent diabetes, obesity, osteoporosis, and cancer. However, the mechanism of the antidiabetic activity of inulin has not yet been elucidated. In this study, we showed that inulin increased the uptake of glucose in C2C12 myotubes, which was associated with both AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but both of these pathways appeared to transmit their signals in an independent manner. Moreover, we found that inulin was able to increase the uptake of glucose in C2C12 myotubes in which insulin resistance was induced by exposing cells to high glucose concentrations. The identical effects of inulin were also observed in HepG2 hepatoma cells. Collectively, we report the antidiabetic activity of inulin and further demonstrate for the first time that such activity is associated with AMPK and PI3-K activation.

Our previous studies, using cDNA microarray and real-time reverse transcription-polymerase chain reaction, showed that acetylcholinesterase T subunit (AChET) gene was more abundantly expressed in the hypothalamus of the responder rats that were sensitive to electroacupuncture (EA) in the tail flick latency (TFL) test than in that of the non-responder rats that were insensitive to EA. In this study, we hypothesized that the expression of the AChET gene in the hypothalamus modulates EA analgesia in rats. To explore the hypothesis, we constructed an AChET-encoding adenovirus and a control virus expressing only green fluorescence protein, either of which was then injected into the hypothalamus of Sprague-Dawley rats. The hypothalamic activity of acetylcholinesterase was significantly higher in rats that were injected with the AChET virus than in rats that were injected with the control virus. The basal pain threshold measured by a TFL test was not changed by microinjection of AChET or control virus into the hypothalamus when EA treatment was not conducted. However, the analgesic effect of EA was significantly enhanced from 7 days after microinjection of the AChET virus into the hypothalamus but not after injection of the control virus. Furthermore, expression of the AChET in the hypothalamus did not affect body core temperature, body weight, motor function or learning and memory ability. Taken together, these results suggest that adenoviral expression of the AChET gene in the hypothalamus potentiates EA analgesia in rats without apparent side-effects.

A major satiety hormone, cholecystokinin (CCK) is well known to be released by electroacupuncture (EA) stimulation at certain body sites which elicits profound psychophysiological responses. Previous clinical and animal studies have shown that EA stimulation reduces food intake and body weight in both normal and obese subjects. The aim of the present study was to elucidate the satiety effect of EA stimulation and its mechanism related to CCK in rats. Here we show that EA stimulation at "Zusanli" (ST36) acupoint significantly reduced 30-min and 60-min food intake in 48-h fasted Sprague-Dawley rats, and such effect was reversed by a lorglumide (CCK-1 receptor antagonist, 10mg/kg, i.p.) pretreatment. The ST36 EA stimulation-induced satiety was not observed in CCK-1 receptor knockout, Otsuka Long-Evans Tokushima Fatty rats, but in their controls, Long-Evans Tokushima Otsuka rats. Subdiaphragmatic vagotomy also blocked the satiety effect of ST36 EA stimulation in Sprague-Dawley rats. These results suggest that ST36 EA stimulation elicits satiety in rats and this is mediated by the endogenous CCK signaling pathway.

This study was performed to examine whether electroacupuncture potentiates the neostigmine-induced antiallodynia in neuropathic pain rats. Although intrathecal neostigmine (0.05, 0.1, and 0.3 microg) dose-dependently relieved cold allodynia, 0.3 microg neostigmine caused side effects. The coapplication of 0.1 microg neostigmine and electroacupuncture, however, produced potent antiallodynia, which was parallel to the effect of 0.3 microg neostigmine, without side effects. These results indicate that electroacupuncture can enhance the antiallodynic action of intrathecal neostigmine.

The present study was performed to examine whether the leaves of Saururus chinensis (LOUR.) BAILL (SC), an herb used for the management of various skin diseases including atopic dermatitis (AD) in Eastern countries, inhibited the development of AD-like skin lesions in NC/Nga mice which was induced by repeated application of picryl chloride (PiCl). The efficacy of SC was judged by measurement of skin severity, itching behavior, histological study, serum IgE levels, IL-4 and IFN-gamma in lymph nodes. Oral administration of SC extract to the PiCl-treated NC/Nga mice for 8 weeks (5 d per week) inhibited significantly the development of AD-like skin lesions macroscopically. Histologically, SC inhibited dermatitis changes like hypertrophy, hyperkeratosis, and infiltration of inflammatory cells into epidermis and dermis. The itching behavior and serum IgE level decreased significantly after SC administration. SC administration enhanced IFN-gamma mRNA expression but did not have an effect on IL-4 mRNA expression. These results suggest that SC could inhibit the development of AD-like skin lesions in NC/Nga mice possibly through modulating the Th1/Th2 imbalance by the promoting of Th1 cell response. Thus, SC may be an alternative substance for the management of AD patients.

"Responder" Sprague-Dawley (SD) rats that were sensitive to electroacupuncture (EA) in an acute thermal pain test (i.e. tail flick latency [TFL] test) maintained sensitivity to EA in the warm allodynia test after peripheral nerve injury. Similarly, the "non-responder" SD rats that were insensitive to EA in the TFL test were also insensitive to EA in the allodynia test. The EA-induced analgesic effects in the TFL test were significantly higher in CCK-A receptor deficient, Otsuka Long-Evans Tokushima Fatty (OLETF) rats than in their littermates, Long-Evans Tokushima Otsuka (LETO) rats. Similarly, the anti-allodynic effects of EA were significantly greater in OLETF rats than in LETO rats. These results suggest that the individual differences in the sensitivity of acute pain behavior to EA were maintained in neuropathic pain behavior following peripheral nerve injury, and that CCK-A receptor expression plays an important role in mediating this phenomenon.

Objectives : This research was executed to verify antitumor effect and protective effect on doxorubicin(Doxo)-induced toxicity of Cultivated Wild Ginseng(CWG) and synergic effect of CWG with Doxo in B16/F10 melanomas-bearing C57BL/6 mice. Methods : To evaluate protective effect on doxorubicin(Doxo)-induced toxicity and enhancing effect on the antitumor activity of Doxo, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days, in combination with intraperitoneal injection of Doxo(4 mg/kg) on days 12, 16, 19, to mice subcutaneously inoculated with B16/F10 melanoma cells. In order to investigate antitumor effect of CWG, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days to mice subcutaneously inoculated with B16/F10 melanoma cells. Results : The body weights of melanoma-bearing mice increased following B16/F10 cells inoculation. In contrast, such an increase in body weights was significantly attenuated by Doxo administration. Whereas CWG inhibits the decrease in body weights induced by Doxo. The tumor volume and tumor weights of melanomas-bearing mice dramatically increased following B16/F10 cells inoculation, In contrast, such an increase in tumor volume and tumor weights were significantly attenuated by Doxo or CWG administration. But the synergic effect of CWG with Doxo was not observed. The reduction of cellularity of seminiferous epithelia, level of spermatogonium and spermatid induced by Doxo was recovered by CWG administration. BrdU labeling index of spermatogonium was remarkably decreased in Doxo group but was no change in CWG group. Whereas the incidence and intensity of BrdU labelled spermatocytes and spermatids were increased by CWG administration than those of Doxo group. Conclusions : The obtained results suggest that CWG have antitumor effect and protective effect on doxo-induced testicular toxicity. This effect might be mediated through the supplementation of vital energy.

The present study was performed to determine whether the expression levels of the hypothalamic cholecystokinin (CCK) and its receptors are associated with the responsiveness to high frequency electroacupuncture (EA) analgesia in rats. EA stimulation (100 Hz, 0.5 ms pulse width, 0.2-0.3 mA) was delivered to the Zusanli (ST36) acupoint of male Sprague-Dawley rats for 20 min without anesthetics or holder restraint. The analgesic effect of EA was quantified using a tail flick latency test, and subsequently animals were allocated to responder or non-responder groups. The hypothalamus of rats in each group was dissected and RNA was purified. The mRNA expressions of CCK, and CCK-A and -B receptor were determined by real-time RT-PCR. CCK mRNA levels were not significantly different in the two groups, whereas both CCK-A and -B receptors were significantly more expressed in non-responders. These results suggest that the level of CCK receptor mRNA expression in the hypothalamus, rather than CCK mRNA, has an important relationship with the individual variations to high frequency EA analgesia in rats.

The present study was performed to examine the effects of electroacupuncture (EA) on cold allodynia and its mechanisms related to the spinal adrenergic and serotonergic systems in a rat model of neuropathic pain. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, EA stimulation (2 or 100 Hz) was delivered to Zusanli (ST36) for 30 min. The behavioral signs of cold allodynia were evaluated by the tail immersion test [i.e., immersing the tail in cold water (4 degrees C) and measuring the latency to an abrupt tail movement] before and after the stimulation. And then, we examined the effects of intrathecal injection of prazosin (alpha1-adrenoceptor antagonist, 30 microg), yohimbine (alpha2-adrenoceptor antagonist, 30 microg), NAN-190 (5-HT1A antagonist, 15 microg), ketanserin (5-HT2A antagonist, 30 microg), and MDL-72222 (5-HT3 antagonist, 12 microg) on the action of EA stimulation. Although both 2 Hz and 100 Hz EA significantly relieved the cold allodynia signs, 2 Hz EA induced more robust effects than 100 Hz EA. In addition, intrathecal injection of yohimbine, NAN-190, and MDL-72222, but not prazosin and ketanserin, significantly blocked the relieving effects of 2 Hz EA on cold allodynia. These results suggest that low-frequency (2 Hz) EA is more suitable for the treatment of cold allodynia than high-frequency (100 Hz) EA, and spinal alpha2-adrenergic, 5-HT1A and 5-HT3, but not alpha1-adrenergic and 5-HT2A, receptors play important roles in mediating the relieving effects of 2 Hz EA on cold allodynia in neuropathic rats.

The present study was designed to examine developmental changes of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in periaqueductal gray (PAG) neurons mechanically isolated from young (12- to 18-day) and adult (8- to 12-week) rats. While the frequency of mIPSCs was similar, the current amplitude in adult rats was significantly smaller than in young rats. In the study of mIPSC kinetics, all kinetic parameters except for the fast decay time in adult rats were smaller or shorter than in the case of young rats. The present study demonstrates that a decrease in the amplitude of GABAergic mIPSC during development may result from a decrease in the GABA contents of synaptic vesicles and from changes in the kinetics of postsynaptic GABA-activated Cl− channels.

The purpose of this study is to elucidate the molecular mechanism of anti-inflammatory effect of bee venom (BV), which has been used for the treatment of various inflammatory diseases in oriental medicine. With this aim, we examined the effects of BV on the nitric oxide (NO) production by lipopolysaccharide (LPS) or sodium nitroprusside in RAW264.7 macrophages. We further investigated the effects of BV on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) with RT-PCR in LPS-stimulated RAW264.7 cells. BV suppressed the NO production and decreased the levels of iNOS, COX-2, NF-kappaB and MAPK mRNA in a dose-dependent manner. These results suggest that BV has an anti-inflammatory effect by inhibiting iNOS and COX-2 expression, possibly through suppression of NF-kappaB and MAPK expression.

In vivo whole-cell voltage-clamp recordings were made from substantia gelatinosa (SG, lamina II of the spinal cord) neurons to analyze modality-dependent excitatory and inhibitory synaptic responses and their receptive fields. All SG neurons examined exhibited spontaneous excitatory postsynaptic currents (EPSCs) at a holding potential of −70 mV. Pinch and touch stimuli applied to the skin of the hind limb elicited a barrage of EPSCs. The spontaneous and evoked EPSCs were blocked by superfusing CNQX, a non-NMDA receptor antagonist. At a holding potential of 0 mV, all SG neurons exhibited spontaneous inhibitory postsynaptic currents (IPSCs) which were inhibited by either bicuculline, a GABA A receptor-antagonist, or strychnine, a glycine-receptor antagonist. In most neurons, touch stimuli produced a barrage of IPSCs. These evoked IPSCs were inhibited either by superfusing strychnine or bicuculline. When EPSCs and IPSCs were recorded from the same neurons, the size of receptive fields of evoked IPSCs was larger than that of evoked EPSCs. These results suggest that innocuous mechanical stimulation applied to the skin adjacent to a painful point inhibits mechanical noxious transmission in the SG.

The effects of chemical sympathectomy on moxibustion-induced changes in splenic natural killer (NK) cell cytotoxicity, T and B cell proliferation were studied. Direct moxibustion was applied to the unilateral Zusanli region. NK cell cytotoxicity was suppressed by moxibustion in both vehicle-treated rats and sympathectomized rats. T cell proliferation was not affected by moxibustion. B cell proliferation showed no significant change in vehicle-treated rats, but an increase was seen in sympathectomized rats treated with moxibustion. Sympathectomy alone induced an augmentation of NK cell cytotoxicity and a suppression of T cell proliferation. These results suggest that the sympathetic nervous system (SNS) has no significant role in the mechanism of moxibustion-induced immunomodulation.

The periaqueductal gray (PAG) is the main target site of the opioid-induced analgesia. The present study was designed to examine the roles of protein kinase A (PKA) and C (PKC) in the opioid-induced modulation of the currents activated by an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). The PAG neurons were acutely isolated and voltage-clamped under the nystatin-perforated patch-clamp mode. The GABA-activated current was sensitively blocked by a GABA(A) receptor antagonist, bicuculline, and selectively carried by chloride ions. The GABA(A) receptor-activated Cl(-) current was potentiated by a mu-opioid receptor agonist, [D-Ala(2),N-MePhe(4),Gly(5)-ol]-enkephalin acetate (DAMGO). The GABA response was also potentiated by phorbol-12-myristate-13-acetate (PMA). Pretreatment with PMA occluded the DAMGO potentiation. However, both chelerythrine and 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X) also potentiated the GABA response. Pretreatment with chelerythrine or GF109203X also occluded the DAMGO potentiation. Meanwhile, the GABA response was potentiated by N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89), while not altered by forskolin. Pretreatment with H-89 occluded the potentiation effect of DAMGO on the GABA response. In addition, the DAMGO effect was completely blocked by pretreatment with forskolin. From the result, it can be suggested that activation of mu-opioid receptor potentiates the GABA(A) response through the mediation of PKA inhibition, and that PKC is not directly involved in the action mechanism of DAMGO.

The effectiveness of traditional herbal medicine (THM) as treatment for nasopharyngeal cancer (NPC) has not been clearly demonstrated. The aim of this study is to assess the effectiveness of THM as adjunctive therapies for NPC using the results of randomized controlled trials (RCTs). Five electronic databases, including English and Chinese databases, were systematically searched up to February 2014. All RCTs involving traditional herbal medicine in combination with conventional cancer therapy for NPC were included. Twenty-two RCTs involving 2,298 NPC patients were systematically reviewed. Of these 22 studies, 15 on 1482 patients reported a significant increase in the number surviving patients with survivals of more than 1, 3, or 5 years. Seven studies on 595 patients reported a significant increase in immediate tumor response, and three studies on 505 patients reported a significant decrease in distant metastasis. This meta-analysis of 22 studies suggests that THM combined with conventional therapy can provide an effective adjunctive therapy for NPC. More research and well-designed, rigorous, large clinical trials are required to address these issues

Electroacupuncture (EA) has been reported to modulate natural killer cell (NK cell) activities. Also it is well known that hypothalamus directly mediates the effects of EA on analgesia. Especially lateral hypothalamic area (LHA) is related to splenic NK cell activities. In order to investigate the relationship between hypothalamus and effects of EA on NK cell activity, lesions have been made bilaterally at LHA of Spraque–Dawley rats. Subsequently, NK cell cytotoxities of normal and lesioned rats were measured with 51Cr release immunoassay after EA stimulation for 2 and 14 days. NK cell activity of EA group was significantly higher than sham group. In addition, lesions abolished effects of EA on NK cell activity. These results strongly suggest that LHA is closely related to increase of NK cell activity induced by EA.

The purpose of this study is to determine whether the level of cholecystokinin (CCK) receptor expression causes the differences between the responder and non-responder to electroacupuncture mediated analgesic effects. Male Sprague-Dawley rats were stimulated at the Zusanli (ST36) acupoint in the absence of any anesthetics and holders. The tail flick latency test was performed to quantify analgesic effects and then the responder and non-responder groups were classified. The hypothalamus of each group was dissected and RNA was purified. The amount of mRNA expression of CCK-A and CCK-B receptors was determined by reverse transcription-polymerase chain reaction. The results show that CCK-A receptors are significantly more expressed in non-responders than responders, whereas CCK-B receptor expression is similar in both groups.

The analgesic effects of acupuncture on the mechanical allodynia in the rat model of neuropathic pain have not yet been studied. The aim of the present study is: first, to determine if electroacupuncture (EA) or morphine attenuates the mechanical allodynia; and secondly, to examine if the EA effect may be mediated by endogenous opioids. To produce neuropathic pain, the right superior caudal trunk was resected between the S3 and S4 spinal nerves. Twenty-one days after the neuropathic surgery, low frequency EA stimulation (2 Hz, 0.3 ms, 0.07 mA) delivered to Houxi (S13) for 30 min relieved significantly the signs of mechanical allodynia. Intraperitoneal (i.p.) morphine (0.5 or 1.5 mg/kg) also relieved the signs of mechanical allodynia in a dose-dependent manner. In addition, the antiallodynic effect of Houxi EA was blocked by pretreatment with naloxone (2 mg/kg, i.p.). However, combined application of EA and morphine did not show an obvious synergistic effect. These results suggest that low frequency EA or morphine can relieve the mechanical allodynia signs and the EA effect can be mediated by endogenous opioid systems.

Background Oxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats. Methods The behavioral signs of cold allodynia in Sprague–Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat’s tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment. Results The serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 μg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 μg, i.t.) or ketanserin (5-HT2A receptor antagonist, 30 μg, i.t.) did not. Conclusions These results suggest that BVA treatment alleviates oxaliplatin-induced acute cold allodynia in rats via activation of the serotonergic system, especially spinal 5-HT3 receptors. Thus, our findings may provide a clinically useful evidence for the application of BVA as an alternative therapeutic option for the management of peripheral neuropathy, a dose-limiting side effect that occurs after an administration of oxaliplatin.

Summary Background The effectiveness of traditional herbal medicine (THM) as an adjunctive therapy for cancer pain is unclear. Objective To assess the effectiveness of THM as an adjunctive therapy for cancer pain using randomized controlled trials (RCTs). Methods Five electronic databases, including those from the UK and China, were systematically searched for the period before September 2013. All RCTs involving the use of THM in combination with conventional cancer therapy for cancer pain were included. Results Twenty-four RCTs involving 4889 patients with cancer pain were systematically reviewed. Among them, nine studies of 952 patients reported a significant decrease in the number of patients with cancer pain in the treatment group. Four studies of 1696 patients reported a significant decrease in the degree of pain in the treatment group. Conclusion The results of these studies suggest that THM combined with conventional therapy is efficacious as an adjunctive therapy for patients with cancer pain. However, more research, including well-designed, rigorous, and larger clinical trials, are necessary to address these issues.

The Role of protein kinase C in the modulatory effect of a mu-opioid receptor agonist, [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), on the glycine-gated Cl(-) current was examined in acutely dissociated rat periaqueductal gray neurons. Using the nystatin-perforated patch-clamp technique, the neurons were voltage-clamped at -60 mV. The glycine-gated Cl(-) current (I(Gly)) was sensitive to strychnine. On pretreatment with 1 microM DAMGO, the 30-microM glycine response increased with time and showed a maximum amplitude of 209+/-37% of control. After a protein kinase C activator, phorbol-12-myristate-13-acetate (PMA, 0.1 microM) as pretreatment, I(Gly) increased to 138+/-6% of control. The DAMGO potentiation of I(Gly) was not altered by coapplication with PMA. Although protein kinase C inhibitors, chelerythrine (3 microM) and 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X, 1 microM), did not alter I(Gly), the DAMGO-induced potentiation of I(Gly) was reduced to 161+/-21% or 164+/-31% of the control after coapplication with chelerythrine or GF109203X, respectively. These results indicate that the potentiation of I(Gly) by a mu-opioid receptor agonist is partly mediated by activation of protein kinase C.

5-hydroxytryptamine (5-HT) has been reported to modulate analgesia produced by opioids or electrical stimulation of the periaqueductal gray (PAG). 5-HT increases K+ conductance and inhibits the firing activity of the PAG neurons. We examined the electrophysiological and pharmacological characteristics of the K+ current involved in 5-HT-induced hyperpolarization of dissociated rat PAG neurons. Among the neurons tested, 5-HT activated inward K+ currents in 30-40%, whilst the remaining 60-70% did not respond to 5-HT. 5-HT activated an inwardly rectifying K+ current (I5-HT) in a concentration- and voltage-dependent manner. I5-HT was mimicked by a 5-HT1A receptor selective agonist, 8-OH-DPAT, and was reversibly blocked by a 5-HT1A receptor antagonist, piperazine maleate, but not by a 5-HT2 receptor antagonist, ketanserin. I5-HT was sensitive to K+ channel blockers such as quinine and Ba2+, but insensitive to 4-aminopyridine, Cs+ and tetraethylammonium. I5-HT was inhibited by GDP(beta)s and was irreversibly activated by GTP(gamma)s. I5-HT was significantly suppressed by N-ethylmaleimide and pertussis toxin, but not by cholera toxin. Second messenger modulators such as staurosporin, forskolin, and phorbol-12-myristate-13-acetate did not alter I5-HT. The present study indicates that 5-HT-induced hyperpolarization of the PAG neurons results from activation of the pertussis toxin-sensitive G-protein-coupled inwardly rectifying K+ currents through 5-HT1A receptors.

Background: This study was designed to evaluate the effects of electroacupuncture on sphincter of Oddi (SO) motility in humans and to associate the manometric findings with cholecystokinin (CCK) plasma levels. Methods: Eleven patients (M:F = 5:6) with various kinds of biliary disorders were enrolled. SO motility was monitored with conventional low-compliance, continuous perfusion technique at ERCP (n = 9) or via percutaneous transhepatic cholangioscopy (n = 2). After baseline monitoring for phasic wave contractions of SO, electroacupuncture was applied at a specific acupoint GB 34. A nonspecific acupoint 5 cm away from GB 34 was selected as a control. Manometric parameters of the SO were also measured in 6 subjects during stimulation of the control acupoint. CCK plasma levels were measured during electroacupuncture stimulation. Results: All manometric parameters including basal pressure, amplitude, frequency, and duration of phasic wave contractions of the SO were significantly decreased (p < 0.05) during electroacupuncture stimulation. The inhibition of SO contractility was accompanied by increased CCK plasma levels. After discontinuation of electroacupuncture stimulation, restoration of amplitude and duration to basal conditions was noted. A tendency toward return of SO basal pressure and contractile frequency to baseline was also observed. Stimulation of the control acupoint did not affect SO contractility. Conclusion: Electroacupuncture stimulation of acupoint GB 34 resulted in reversible inhibition of SO contraction in humans. The response of SO to electroacupuncture stimulation may be mediated by some neurohormonal mechanisms including CCK release.

The method of quick insertion and withdrawal of the needle (QIW) in acupuncture is a technique of stimulation not retaining the needle in the acupuncture point. We examined the analgesic effects of five different types of QIW along with the changes of stimulation quantity, time, and depth, and then compared the analgesic effect of the most effective QIW to that of plain acupuncture (PA). When tail-flick latency values between the strongest QIW-I group and PA group were compared, there was no significant difference (analyzed by t-test). These results indicate that QIW technique has an analgesic effect similar to PA technique and that the conditions, which for the QIW-I was shown the most effective analgesia, are a duration of 5 s at intervals of 1 s and at the depth of 3 mm.

Plain acupuncture uses manipulation (rotation or varying the depth of insertion of the needle) to increase its effect. However, in commonly used electroacupunture (EA), variable manipulations have not been used. This study was performed to investigate the possibility of an increase in analgesic effect by adding manipulation to EA. The pain index used was the Tail-Flick latency (TFL) of the rat, which was lightly anesthetized with thiopental sodium (intraperitoneally). Four types of manipulation were used. Rotation and varying the depth of the needle (RN and VN) was employed using two different types of manipulation during each 20 min stimulation of EA. Each manipulation persisted for 1 min out of every 5 min (long - duration and long - interval: LDLI) or 12 s every 1 min (short - duration and short interval: SDSI). EA produced an increase in TFL; peak value was 49.7+/-12.2% of the pre - EA and occurred immediately after cessation of 20 min of EA stimulation. Performing RN or VN combined with EA also increased TFL more than just EA and a greater peak increase in TFL was observed with a SDSI - RN and SDSI - VN as compared to a LDLI - RN and LDLI - VN (77.5+/-13.8, 79.2+/-19.8 and 67.3+/-14.0%, 65.6+/-23.7% of the pre - EA, respectively). These results indicate that manipulation combined with EA produces a more potent antinociception than when only EA is applied.

In neuropathic rats sensitive to phentolamine (alpha-adrenoreceptor antagonist, 2 mg/kg, i.p.), prazosin (alpha1-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) significantly attenuated cold allodynia whereas yohimbine (alpha2-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) had no significant effect. In neuropathic rats insensitive to phentolamine, yohimbine significantly exacerbated cold allodynia whereas prazosin had no significant effect. These results suggest that the individual differences in the sensitivity of cold allodynia to phentolamine may be due to the difference in the alpha-adrenoreceptor subtype predominantly involved in cold allodynia.

Ethnopharmacological relevance PM014 is a modified form of the Chung-Sang-Bo-Ha-Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary diseases in Korea for centuries. Previously, we developed a formulation of PM014 based on a series of in vitro and in vivo screening efforts that comprises seven herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria baicalensis and the root of Stemona sessilifolia. Asthma is a chronic inflammatory disease of the lungs that is characterized by wheezing, bronchial contraction, and chest tightness. In addition, the airway becomes hypersensitive and narrows through an inflammatory reaction mediated by Th2 cells. The present study was conducted to evaluate the ability of PM014 to prevent allergic airway inflammation and to attenuate airway responses in a cockroach allergen-induced mouse model. Materials and methods Mice sensitized to and challenged with cockroach allergen were treated with oral administration of PM014. Airway resistance was determined by whole body plethysmography. In addition, Th2 cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and inflammatory mediators in serum were analyzed by ELISA. A series of histological examinations were also conducted to demonstrate the effects of PM014 on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Results PM014 significantly inhibited the number of total cells, eosinophils, neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis also showed that PM014 substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. Conclusions In this study, our results indicate that PM014 has significant effects on allergic airway inflammation upon exposure to cockroach allergen in a mouse model. According to these outcomes, PM014 may have therapeutic potential as a treatment for allergic asthma.

Neuropathic pain remains as one of the most difficult clinical pain syndromes to treat. Electroacupuncture (EA), involving endogenous opioids and neurotransmitters in the central nervous system (CNS), is reported to be clinically efficacious in various fields of pain. Although multiple experimental articles were conducted to assess the effect of EA-induced analgesia, no review has been published to assess the efficacy and clarify the mechanism of EA on neuropathic pain. To this aim, this study was firstly designed to evaluate the EA-induced analgesic effect on neuropathic pain and secondly to guide and help future efforts to advance the neuropathic pain treatment. For this purpose, articles referring to the analgesic effect of acupuncture on neuropathic pain and particularly the work performed in our own laboratory were analyzed. Based on the articles reviewed, the role of spinal opioidergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors in the mechanism of EA-induced analgesia was studied. The results of this research demonstrate that μ and δ opioid receptors, α 2-adrenoreceptors, 5-HT1A and 5-HT3 serotonergic receptors, M1 muscarinic receptors, and GABAA and GABAB GABAergic receptors are involved in the mechanisms of EA-induced analgesia on neuropathic pain.