The analgesic effects of ß-elemene in rats with neuropathic pain by inhibition of spinal astrocytic ERK activation.

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.

Effect of electroacupuncture stimulation at Zusanli acupoint (ST36) on gastric motility: possible through PKC and MAPK signal transduction pathways.

BACKGROUND: Electroacupuncture (EA) stimulation has been shown to have a great therapeutic potential for treating gastrointestinal motility disorders. However, no evidence has clarified the mechanisms contributing to the effects of EA stimulation at the Zusanli acupoint (ST.36). This study was designed to investigate the regulative effect of EA stimulation at the ST.36 on gastric motility and to explore its possible mechanisms. METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups: the ST.36 group, the non-acupoint group, and the control group. EA stimulation was set at 2 Hz, continuous mode, and 1 V for 30 min. The frequency and average peak amplitude of gastric motility were measured by electrogastrography. The protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling pathways were assessed using real-time polymerase chain reactions. Caldesmon (CaD) and calponin (CaP) protein expression in the gastric antrum were detected on Western blots. A Computed Video Processing System was used to evaluate morphological changes in smooth muscle cells (SMCs) from the gastric antrum. RESULTS: EA stimulation at ST.36 had a dual effect on the frequency and average peak amplitude. Additionally, EA stimulation at ST.36 regulated the expression of some genes in the PKC and MAPK signaling pathways, and it regulated the expression of the CaD and CaP proteins. EA serum induced SMC contractility. Promotion of gastric motility may correlate with up-regulation of MAPK6 (ERK3), MAPK13, and Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression, and the down-regulation of the collagen, type I, alpha 1 (COL1A1) gene and CaD and CaP protein expression. Inhibition of gastric motility may correlate with down-regulation of the Interleukin-1 receptor type 2 (IL1R2) and Matrix metalloproteinase-9 (MMP9) genes, and up-regulation of CaD and CaP protein expression. CONCLUSIONS: EA stimulation at ST.36 regulated gastric motility, and the effects were both promoting and inhibiting in rats. The possible mechanisms may correlate with the PKC and MAPK signal transduction pathways.

Iron deposition in the precentral grey matter in patients with multiple sclerosis: a quantitative study using susceptibility-weighted imaging.

PURPOSE: Several studies suggest that iron deposition may play a role in multiple sclerosis (MS) pathology. Three-dimensional (3D) enhanced T2*-weighted angiography (ESWAN) at 3T was used to quantify iron deposition in the precentral grey matter in MS and its relationship with disease duration, atrophy and Expanded Disability Status Scale (EDSS) scores. METHODS: We recruited 33 patients with diagnosis of clinically definite MS and 31 age- and sex-matched healthy controls who underwent conventional brain MRI, 3D-ESWAN and 3D T1sequences. We obtained the mean phase values (MPVs) of the precentral grey matter on ESWAN-filtered phase images and volume of the precentral gyrus on 3D T1 images. We investigated the correlation between precentral grey matter MPVs, precentral gyrus volume, disease duration and EDSS scores of MS patients and healthy controls. RESULTS: The precentral grey matter MPVs in MS patients and controls were 1870.83 ± 56.61 and 1899.22 ± 51.73 respectively and had significant difference in the MS group vs. the control group (t=-2.09, P=0.04). There was significant negative correlation between precentral grey matter MPVs and disease duration (r=-0.365, P=0.03). No correlation was found between MPVs and EDSS scores. Mean precentral gyrus volume in MS patients was 4368.55 ± 867.78 whereas in controls was 5701.00 ± 1184.03 with significant difference between volume of the precentral gyrus in MS patients compared to healthy controls (t=-5.167, P<0.001). There was a positive correlation between MPVs and precentral gyrus volume (r=0.291, P=0.020). CONCLUSIONS: Our study demonstrated that quantitative assessment of abnormal iron deposition in the precentral grey matter in MS patients can be measured using 3D-ESWAN.

Disruption of glial function regulates the effects of electro-acupuncture at Tsusanli on gastric activity in rats.

According to recent evidence, acupuncture at Tsusanli (ST 36) can regulate gastric activity. And this regulation mainly depends upon neural basis or structure and may probably relate to the central neurons in the dorsal vagal complex. However, whether the glias of the dorsal vagal complex participate in the regulation of gastric activity, when electro-acupuncture (EA) at Tsusanli, still remains to be interpreted. In this study, we observed the effect of EA at Tsusanli (ST 36) on regulation of gastric activity. Propentofylline (PPF), a glial metabolic inhibitor, was used to inhibit the function of glial cells. EA at Tsusanli showed that the expressions of glial fibrillary acidic protein (GFAP) and OX42 increased significantly compared to that of the control group, and gastric electric change was obvious, with significantly higher frequency and wave amplitude compared to the control group. The expressions of GFAP and OX42 were decreased markedly when pretreated with PPF group than without PPF pretreatment group. Compared to the Tsusanli group and the control group, the changes of electro gastric graph (EGG) were significantly decreased in PPF pretreatment group. On the other hand, we observed the changes of spontaneous electro-activity of the DVC (dorsal vagal complex) in our previous experiment. The results indicated that EA at Tsusanli could activate glial cells in the dorsal vagal complex and regulate gastric activity. PPF blocked the function of glia, thus the effect of EA at Tsusanli on gastric activity was weakened. Our study suggested that this electro-acupuncture regulation of gastric activity was possibly related with glia of the dorsal vagal complex.

[Changes in plasticity of rat hypothalamic neurons and astrocytes in humid and hot environment].

OBJECTIVE: To study the changes in the plasticity of the neurons and astrocytes in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus of rats exposed to a humid and hot environment. METHODS: The rats were subjected to stimulation with a humid and hot environment for 120 min in a climate chamber (dry bulb temperature of 40.0-/+0.5 degrees C with relative humidity of 60-/+5%). During the exposure, the behavioral responses of the rats were observed, and the changes in the expressions of Fos and GFAP in the PVN and SON in response to the exposure evaluated using immunohistochemical ABC methods. RESULTS: Exposure to a humid and hot environment caused restlessness and agitation in the rats, which showed increased respiratory frequency and scratching of the face with the forelimbs. Two rats died after the 120-min exposure. Significantly increased expressions of Fos and GFAP were detected in the PVN and SON following the exposure as compared with the control group. CONCLUSION: The neurons and astrocytes in the PVN and SON both participate in the regulation of responses to exposure to a humid and hot environment.

Electro-acupuncture of Tsusanli and Shangchuhsu regulates gastric activity possibly through mediation of the vagus-solotary complex.

BACKGROUND/AIMS: Acupuncture has been reportedly used to treat gastrointestinal diseases, however, its precise mechanism remains unknown. METHODOLOGY: In our study, the effects and mechanism of electro-acupuncture (EA) at Tsusanli (ST 36), Shangchuhsu (ST 37) on regulation of gastric activity were observed. RESULTS: EA at Tsusanli showed that gastric electric change was the most obvious, with significantly higher frequency and wave amplitude compared with that of the Shangchuhsu group and other groups. EA at Shangchuhsu demonstrated that the change of gastric electric level was much higher than that of the non-acupoint group and control group. After bilateral vagotomy, Tsusanlis was electro-acupunctured, the changes of electro-gastric graph (EGG) weren't significant with the control group. The frequency of electro-physiological activity in nucleus of solitary tract (NTS) and dorsal motor nucleus of the vagus nerve (DMV) in the Tsusanli group was markedly increased compared with that in the other group. Fos and GFAP expression in NTS and DMV in the Tsusanli group was significantly higher than that in other groups and control group. The results have indicated that EA at Tsusanli and Shangchuhsu cannot only regulate gastric activity, but also activate neurons and astrocytes in NTS and DMV. The effects on regulation and activation of EA at Tsusanli were very obvious. CONCLUSIONS: Our study suggests that this electroacupuncture regulation of gastric activity may partially depend upon integrated nerve pathway and related central neurons and astrocytes in the vagus-solitary complex.

[Influence of intrathecal injection of fluorocitrate on the protective effect of electroacupuncture on gastric mucosa in high humid heat stress rats].

OBJECTIVE: To study if the spinal glial cells involve in the protective effect of acupuncture on gastric mucosa in high humid heat stress rats. METHODS: Thirty-six male SD rats were randomized into 6 groups: control, stress model, electroacupuncture (EA), Fluorocitrate(FCA, intrathecal injection of FCA. 1 microL, 60 min before humid heat stress), EA+ normal saline (NS, intrathecal injection of NS) and EA+ FCA groups. Stress model was established by putting the rats in a container with higher temperature and higher humidity [(40.0 +/- 0.5) degrees C, relative humidity (60 +/- 5)%] for 60 min. EA (50 Hz, intermittent waves, 2-5 V) was applied to bilateral "Zusanli" (ST 36) for 60 min. Using immunofluorescent methods, we observed glial fibrillary acidic protein (GFAP) and microglia OX42 immunoreactivity (OD value) in the tissue of the lumbar enlargement segment of the spinal cord. We evaluated and recorded the damage index (DI) of gastric mucosa of rats according to Guth's method. RESULTS: There were clear dot-line-like hemorrhage foci with formation of ulcer in the gastric mucosa 60 minutes after high humid heat stimulation. Compared with model group, DI of gastric mucosa in EA and EA+ NS groups decreased significantly (P < 0.05, suggesting a protective effect of EA on the gastric mucosa under stress), OD values of EA and EA + NS groups increased considerably (P < 0.05). Comparison between EA and EA+ FCA groups showed that DI of EA + FCA group was higher than that of EA group, while the OD values of GFAP and OX42 in EA+ FCA group was markedly lower than those in EA group (P < 0.05), suggesting an inhibitory effect of FCA on the effects of EA in improving stress-induced damage of gastric mucosa and upregulation of GFAP and OX42 expression. CONCLUSION: EA at "Zusanli" (ST 36) can prevent the gastric mucosa from injury caused by high humid heat stimulation. The lumbar spinal glial cells may play a role in EA's protective function.

Electro-acupuncture of Foot YangMing regulates gastric activity possibly through mediation of the dorsal vagal complex.

Acupuncture at some specific acupoints of Foot Yangming can regulate gastric activity. However, its precise mechanism remains unknown. In our study, the effects and mechanism of electro-acupuncture (EA) at Tsusanli (ST 36), Shangchuhsu (ST 37) on the regulation of gastric activity were observed. EA at Tsusanli showed that gastric electric change had a significantly higher frequency and wave amplitude as compared to that of the Shangchuhsu group and other groups. EA at Shangchuhsu demonstrated the change of gastric electric was greater than that of the non-acupoint group and the control group. After bilateral vagotomy, the change of electro gastric graph (EGG) of EA at Tsusanlis was not significant compared to the control group. In the mean time, we have observed the electric discharge of the neurons in NTS and DMV. The frequency of electro-physiological activity in nucleus of solitary tract (NTS) and dorsal motor nucleus of the vagus nerve (DMV) in Tsusanli group and Shangchuhsu group were markedly increased compared with that in other groups. The results have indicated that EA at Tsusanli and Shangchuhsu not only regulate gastric activity, but also activate neurons in NTS and DMV significantly. Our study suggests that the effect of EA at Tsusanli and Shangchuhsu on the gastric activity may partially depend upon integrated nerve pathway and related central neurons in dorsal vagal complex.

[Effect of intraoperative using cell saver on blood sparing and its impact on coagulation function].

OBJECTIVE: To observe the effectiveness of using cell saver (CS) during surgery on blood sparing and its impact on patient's hematology and coagulation function. METHODS: One-hundred and thirty-eight patients undergoing elective surgery were recruited for intraoperative blood salvage using CS. Blood routine, blood chemistry and coagulation function were measured before surgery, after infusion of salvaged blood and postoperative day 1, respectively. RESULTS: In total, 112,056 ml of packed red blood cells were collected, with a mean value of 812 ml per patient. The percentage of autologous blood transfusion volume to the total blood transfusion volume was from 48% to 89%. Allogenic blood transfusion rate was from 5% to 100%. Compared with the values before surgery, the hemoglobin concentration, platelet count, plasma total protein and fibrinogen concentration decreased significantly after the transfusion of salvaged blood and the first postoperative day (P < 0.05 or P < 0.01), while the prothrombin time was significantly prolonged (P < 0.05). CONCLUSIONS: The use of CS during surgery can, to a certain extent, reduce the requirement of allogenic blood. However, reinfusion of large amount of salvaged blood may affect coagulation function.