Effect Of Electroacupuncture Treatment Research Articles

Electroacupuncture treatment improves postoperative ileus by inhibiting the Th1 cell-mediated inflammatory response through the vagus nerve.

Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI. Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1β, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4+ interferon (IFN)-γ+ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN). The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI. Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

The regulatory effects of electroacupuncture on type 2 innate lymphoid cell (ILC2) function and browning of white adipose tissue in obese rats: 电针通过调控ILC2功能和白色脂肪棕色化治疗肥胖大鼠的作用机制

ObjectiveTo observe the effects of electroacupuncture (EA) on type 2 innate lymphoid cell (ILC2) function in white adipose tissue (WAT) of high-fat diet (HFD)-induced obese rats to reveal the mechanism underlying weight loss. MethodsMale Winstar rats (n=15) were randomly divided into control, HFD, and HFD+EA groups, with five rats in each group. An obesity model was established by feeding rats with a HFD. EA (2 Hz, 1 mA) was applied to “Zhongwan (CV12)” bilateral “Tianshu (ST25)” “Zusanli (ST36)” and “Sanyinjiao (SP6)” for 15 min, 7 days a week, for a total of 5 weeks. During EA treatment, the HFD group was fed a HFD, whereas rats in the control group were maintained on a normal diet. There was no intervention in either the control or the HFD groups. Body weight was measured weekly. Full-field adipocyte morphology, adipocyte volume, and the number of abdominal WAT were observed under a microscope after sectioning and hematoxylin and eosin staining. The levels of IL-5 (interleukin-5), IL-13 (interleukin-13), IL-33 (interleukin-33), and ST2 (growth stimulating gene 2 protein) in the WAT were assayed using enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of browning markers including PGC1α（peroxisome proliferator-activated receptor gamma coactivator 1-alpha）, PPARγ (peroxisome proliferator-activated receptor gamma), PRDM16 (histone-lysine N-methyltransferase), and UCP1（uncoupling protein 1 in WAT were detected by western blot analysis and RT-PCR. ResultsAfter a 7-week induction period, rats in both the HFD and HFD+EA groups were 20% heavier than their initial weights before modeling (P<0.01, P<0.001). Following a 5-week EA intervention, the body mass and Lee index of obese rats were significantly reduced (P<0.05). The HE results showed that adipocytes in the HFD group displayed a significant increase in diameter and a decrease in number compared to the control group. However, in the HFD+EA group, white adipocytes exhibited reduced diameter and appeared more regular in shape. In the control group, the proportion of ILC2 was (86.53±2.55)%, whereas in the HFD group, it decreased to (73.62±2.52)%, indicating a significant reduction in ILC2 in the WAT of obese rats. Following EA treatment, the proportion of ILC2 was elevated to (80.54±4.25)%. This analysis revealed a significant decrease in the expression levels of IL-5, IL-13, IL-33, and ST2 in the WAT of obese rats in the HFD group; however, these levels increased after EA intervention. The mRNA levels of PPARγ, PGC1α, PRDM16, and protein levels of UCP1 were decreased in the HFD group (P<0.01, P<0.05, and P<0.001), and the trends were significantly reversed with EA manipulation (P<0.05). RT-PCR and western blotting results revealed that EA remarkably upregulated the mRNA expression of PGC1α, PPARγ, and PRDM16, as well as the protein expression of UCP1 induced by HFD. In the HFD group, PRDM16 expression showed a strong correlation with UCP1 expression, and ILCs were strongly correlated with PGC1α expression. However, these strong correlations did not occur in HFD+EA group. Following EA treatment, the expression of PPARγ displayed a strong correlation with ILC2s, indicating that the altered ILC2 proportion was closely related to browning in WAT. ConclusionEA treatment effectively alleviated obesity by restoring ILC2 function and promoting browning of white adipocytes. ILC2s may play an important role in the effects of EA treatment, but this requires further study.

Effect of Electroacupuncture with Different Current Intensities on the Serum Metabolomics of Functional Constipation.

The aim of the study is to investigate the serum metabolomics of electroacupuncture (EA) with different current intensities in the treatment of functional constipation (FC). The total number of FC patients was 19, (7, 6, 6, in the low current intensity group (LCI), high current intensity group (HCI), and mosapride citrate tablet control group (MC), respectively). Patients in the EA groups received 16 sessions of acupuncture treatments. Patients in the MC group were orally administered 5 mg mosapride citrate tablets 3 times daily, and serum samples were collected from the patients before and after treatment. Orthogonal partial least square-discriminant analysis (OPLS-DA) was used to assess the metabolic data. The significant differences before and after FC treatment are shown in the OPLS-DA score plot. Variable importance plots (VIPs) and T tests were used to identify significant metabolites. Among the three groups, the number of metabolites with VIP > 1 was 11, 7, and 21 (in LCI, HCI and MC groups, respectively). Compared with those before treatment, the serum metabolites of patients were characterized by increased levels of L-ornithine (p < 0.05) and glyceric acid in the LCI group (p < 0.05), increased levels of vanillic acid in the MC group (p < 0.05), and decreased levels of arabinonic acid in the MC group (p < 0.05). The effects of EA treatment on the serum metabolomics of FC may involve fatty acid and amino acid metabolism.

The Effect of Electroacupuncture Treatment with Different Intensities for Functional Diarrhea: A Randomized Controlled Trial.

Background Electroacupuncture (EA) may have a role in the treatment of diarrhea symptoms. However, the efficacy and safety of EA with different current intensities in improving gastrointestinal function, psychology, and quality of life (QOL) of functional diarrhea (FD) remain unknown. Objective To investigate the efficacy and safety of EA with different current intensities in improving gastrointestinal function, psychology, and QOL for FD patients. Methods 73 FD patients were randomly divided into three groups: low current intensity group (LI) of EA, high current intensity group (HI) of EA, and loperamide control group (LC). Four weeks of treatment were provided in the three groups. The primary outcome was the proportion of normal defecation. Additional outcomes included the change from baseline for the weekly spontaneous bowel movements (SBMs) and the change from baseline for the mean Bristol Stool Form Scale (BSFS). QOL was assessed by the 36-item short-form health survey (SF-36). Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to assess the psychology state. Results Low current intensity of EA significantly improved the proportion of normal defecation during treatment and follow-up period (P < 0.01). EA significantly improves the mean BSFS scores and weekly SBMs, and this efficacy is equivalent to loperamide (P < 0.05). The SF-36 scores of general health in LI and HI groups and vitality and mental health in LI group were significantly increased compared to baseline (P < 0.05). Low current intensity of EA can significantly improve SAS and SDS scores (P < 0.05). Conclusions EA significantly improved stool consistency and weekly SBMs in FD patients. Compared with loperamide, low current intensity of EA may have a better sustainable effect in restoring normal defecation in patients with FD, and it can also effectively improve QOL, anxiety, and depression. However, larger sample sizes are needed to determine safety and efficacy. Trial registration number: NCT01274793.

Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction.

Acupuncture at acupoints Baihui (GV20) and Dazhui (GV14) has been shown to promote functional recovery after stroke. However, the contribution of the contralateral primary sensory cortex (S1) to recovery remains unclear. In this study, unilateral local ischemic infarction of the primary motor cortex (M1) was induced by photothrombosis in a mouse model. Electroacupuncture (EA) was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques. Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction. Intrinsic neuronal excitability and activity were also disturbed, which was rescued by EA. Furthermore, the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1. We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction. Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction. The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine (approval No. 20200407009) April 7, 2020.

Integrated Bioinformatics Analysis of Potential mRNA and miRNA Regulatory Networks in Mice With Ischemic Stroke Treated by Electroacupuncture.

Background: The complicated molecular mechanisms underlying the therapeutic effect of electroacupuncture (EA) on ischemic stroke are still unclear. Recently, more evidence has revealed the essential role of the microRNA (miRNA)–mRNA networks in ischemic stroke. However, a systematic analysis of novel key genes, miRNAs, and miRNA–mRNA networks regulated by EA in ischemic stroke is still absent.Methods: We established a middle cerebral artery occlusion (MCAO) mouse model and performed EA therapy on ischemic stroke mice. Behavior tests and measurement of infarction area were applied to measure the effect of EA treatment. Then, we performed RNA sequencing to analyze differentially expressed genes (DEGs) and functional enrichment between the EA and control groups. In addition, a protein–protein interaction (PPI) network was built, and hub genes were screened by Cytoscape. Upstream miRNAs were predicted by miRTarBase. Then hub genes and predicted miRNAs were verified as key biomarkers by RT-qPCR. Finally, miRNA–mRNA networks were constructed to explore the potential mechanisms of EA in ischemic stroke.Results: Our analysis revealed that EA treatment could significantly alleviate neurological deficits in the affected limbs and reduce infarct area of the MCAO model mice. A total of 174 significant DEGs, including 53 upregulated genes and 121 downregulated genes, were identified between the EA and control groups. Functional enrichment analysis showed that these DEGs were associated with the FOXO signaling pathway, NF-kappa B signaling pathway, T-cell receptor signaling pathway, and other vital pathways. The top 10 genes with the highest degree scores were identified as hub genes based on the degree method, but only seven genes were verified as key genes according to RT-qPCR. Twelve upstream miRNAs were predicted to target the seven key genes. However, only four miRNAs were significantly upregulated and indicated favorable effects of EA treatment. Finally, comprehensive analysis of the results identified the miR-425-5p-Cdk1, mmu-miR-1186b-Prc1, mmu-miR-434-3p-Prc1, and mmu-miR-453-Prc1 miRNA–mRNA networks as key networks that are regulated by EA and linked to ischemic stroke. These networks might mainly take place in neuronal cells regulated by EA in ischemic stroke.Conclusion: In summary, our study identified key DEGs, miRNAs, and miRNA–mRNA regulatory networks that may help to facilitate the understanding of the molecular mechanism underlying the effect of EA treatment on ischemic stroke.

Effect of electroacupuncture treatment on functional constipation in adults: A protocol for systematic review.

Background:Electroacupuncture has been widely used to treat functional constipation. But its efficiency has not been scientifically and methodically evaluated. The objective of this study is to evaluate the efficiency and safety of the electroacupuncture treatment for functional constipation in adults.Methods:This protocol of systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will conduct the literature searching in the following electronic databases: the Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, the Chinese Science Citation Database (CSCD), China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), Wanfang, and the Chinese Scientific Journal Database (VIP). The time limit for retrieving studies is from establishment to July 2020 for each database. All published randomized controlled trials (RTCs) related to this review will be included. Review Manager (V.5.3.5) will be implemented for the assessment of bias risk and data analyses. The selection of the studies, data abstraction, and validations will be performed independently by 2 researchers.Results:This review will assess the clinical efficacy and safety, as well as the acupoints characteristics of electroacupuncture on functional constipation (FC) in adults.Conclusion:This review will summarize the current evidence of electroacupuncture on FC outcomes and provide guidance for clinicians and patients to select electroacupuncture for FC in adults.Trail registration number:This protocol of systematic review has been registered on PROSPERO website (No. CRD42019146715).

Electroacupuncture for alleviation of phantom limb pain

Phantom limb pain is clinically defined as the perception of pain or discomfort in a limb that no longer exists. Most amputees will experience phantom limb pain, which is associated with a low health-related quality of life. Phantom limb pain represents an important challenge in finding an effective therapy. The scientific evidence for best practice is weak, and is characterized by various clinical reports describing the pragmatic use of drugs and interventional techniques. Recent approaches to restore the sensory motor input have shown promise. One such technique is electroacupuncture. We report here a case study of a male in his 30s who sustained severe injuries, including a high transfemoral amputation, as a result of being hit by a car. An electroacupuncture treatment protocol was used. Over the course of 3 months, electroacupuncture alleviated the patient’s phantom limb pain, minimized his use of drugs, and improved his sleep and quality of life. The effect of electroacupuncture treatment lasted for 3–4 months, and successful top-up treatment maintained his pain relief. The results are in line with a study comparing massage and electroacupuncture in patients with spinal cord injury with neurogenic pain; a limited number of patients treated with electroacupuncture were significantly alleviated of their pain for months. This case report suggests that electroacupuncture may be useful in patients with phantom limb pain.LAY ABSTRACTSince phantom limb pain was first described by the French military surgeon Ambroise Pare in the 16th century, the number of studies has increased every year. Although many hypotheses have been proposed regarding the mechanisms of pain and many treatments approaches tried, there is a lack of successful treatments to induce long-term pain relief, improve sleep and quality of life in patients with phantom limb pain. A novel treatment approach used in patients with spinal cord injury pain is electroacupuncture. This case report used a long-term electroacupuncture protocol in a patient with phantom limb pain.

Electroacupuncture reduces scopolamine-induced amnesia via mediating the miR-210/SIN3A and miR-183/SIN3A signaling pathway

BackgroundThe expression of SIN3A is closely correlated with electroacupuncture (EA) treatment efficacy of scopolamine-induced amnesia (SIA), but its underlying mechanisms remain to be further explored.MethodsQuantitative real-time PCR was performed to analyze the expression of candidate microRNAs (miRNAs) and SIN3A mRNA in a rat model of SIA. Western blot was carried out to evaluate the differential expression of SIN3A proteins under different circumstances. Luciferase assay was used to explore the inhibitory role of certain miRNAs in SIN3A expression. A novel object recognition (NOR) test was performed to assess the memory function of SIA rats undergoing EA treatment. Immunohistochemistry was carried out to evaluate the expression of SIN3A in the hippocampus of SIA rats.ResultsRno-miR-183-5p, rno-miR-34c-3p and rno-miR-210-3p were significantly up-regulated in SIA rats treated with EA. In addition, rno-miR-183-5p and rno-miR-210-3p exerted an inhibitory effect on SIN3A expression. EA treatment of SIA rats effectively restored the dysregulated expression of rno-miR-183-5p, rno-miR-210-3p and SIN3A. EA treatment also promoted the inhibited expression of neuronal IEGs including Arc, Egr1, Homer1 and Narp in the hippocampus of SIA rats. Accordingly, the NOR test also confirmed the effect of EA treatment on the improvement of memory in SIA rats.ConclusionIn summary, the findings of this study demonstrated that scopolamine-induced amnesia was associated with downregulated expression of miR-210/miR-183 and upregulated expression of SIN3A. Furthermore, treatment with EA alleviated scopolamine-induced amnesia in rats and was associated with upregulated expression of miR-210/miR-183 and downregulated expression of SIN3A.

Effect of Electroacupuncture Treatment at Dazhui (GV14) and Mingmen (GV4) Modulates the PI3K/AKT/mTOR Signaling Pathway in Rats after Spinal Cord Injury.

Electroacupuncture (EA) is widely recognized as clinical treatment of spinal cord injury (SCI). The purpose of this study is to elucidate whether and how the PI3K/AKT/mTOR signaling pathway plays any role in EA treating SCI. Rats were randomly divided into four equal groups: Control Group, Sham-operation Group, Model Group, and EA Group, then further randomly divided into the following subgroups: 1-day (n = 12), 1-day rapamycin (n = 6), 14-day (n = 18), and 28-day (n = 18). A rat model of SCI was established by a modified Allen's weight-drop method. In the EA Group, rats were stimulated on Dazhui (GV14) and Mingmen (GV4) for 20 min by sterilized stainless steel needles. In the EA Group, the Basso, Beattie, and Bresnahan locomotor rating scale showed obvious improved locomotor function, and hematoxylin-eosin staining and magnetic resonance imaging showed that the histological morphology change of injured spinal cord tissue was obviously alleviated. Also, blocking spinal mTOR by injection of rapamycin showed that mTOR existed in the injured spinal cord, and EA could significantly activate mTOR in SCI rats. And immunohistochemistry and western blot analysis on the PI3K/AKT/mTOR signaling pathway showed that levels of PI3K, AKT, mTOR, and p70S6K in the injured spinal cord tissue were greatly increased in the EA Group, while the levels of PTEN and caspase 3 were decreased. The present study suggests that EA could affect cell growth, apoptosis, and autophagy through the PI3K/AKT/mTOR signaling pathway.

Electroacupuncture Alleviates Osteoarthritis by Suppressing NLRP3 Inflammasome Activation in Guinea Pigs.

Osteoarthritis (OA) is an increasingly prevalent disease affecting synovial joints, which includes joint degeneration, inflammation, and joint pain. The activation of nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) could promote synovial inflammation. Previous studies have shown that electroacupuncture (EA) has potential anti-inflammatory effect. However, the effect of EA treatment on OA remains unclear. The aim of this study was to investigate the effect of applied EA on OA and joint pain and its relationship with NLRP3 inflammasome. The Hartley guinea pigs with naturally occurring OA at age 18 months were chosen as the OA model and treated with EA for 4 weeks. Mechanical allodynia was quantified by using von Frey filaments. The expression of NLRP3 inflammasome and the downstream proinflammatory factors in the cartilage tissue were quantified. Our results showed that EA treatment significantly reduces mechanical allodynia, improves the articular cartilage structure, and decreases the fibrillation on the cartilage surface in guinea pigs with spontaneous osteoarthritis. Moreover, we also found that EA treatment attenuates the NLRP3 inflammasome activation and suppresses the protein expression levels of caspase-1 and IL-1β in the cartilage tissue. Our findings suggest that EA treatment attenuates OA and joint pain by suppressing NLRP3 inflammasome activation and support further investigation of the potential therapeutic tactics.

Circular RNA expression profiling in the nucleus accumbens: Effects of electroacupuncture treatment on morphine-induced conditioned place preference.

Electroacupuncture (EA) has been developed on the basis of traditional Chinese acupuncture. EA can suppress craving in opioid addicts and opioid-seeking responses in rodents. However, the molecular mechanism of EA on the rewarding properties of morphine and craving responses is not known. Here, we have applied a conditioned place preference paradigm in mice to measure morphine-induced rewarding effects along with EA treatment. Circular RNAs (circRNAs) can function as micro RNA (miRNA) sponges to effectively regulate gene expression levels. CircRNA profiling within the nucleus accumbens (NAc) was performed in EA-treated and sham-treated mice. Following RNAseq, data were analyzed by gene ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) tools. We identified 112 significantly differentially expressed circRNAs, including 51 that were up-regulated and 61 that were down-regulated. Our bioinformatics analyses show that these differentially expressed circRNAs map into pathways that are mainly involved with renin secretion and the cGMP-PKG signaling. We further constructed a circRNA-miRNA network that predicts the potential roles of the differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our secondary sequencing and bioinformatics analysis in the NAc after EA treatment on morphine-induced CPP provides putative novel targets on molecular mechanisms involved in morphine reinforcement and possibly craving.

Electroacupuncture Treatment Alleviates the Remifentanil-Induced Hyperalgesia by Regulating the Activities of the Ventral Posterior Lateral Nucleus of the Thalamus Neurons in Rats.

Mechanisms underlying remifentanil- (RF-) induced hyperalgesia, a phenomenon that is generally named as opioid-induced hyperalgesia (OIH), still remain elusive. The ventral posterior lateral nucleus (VPL) of the thalamus, a key relay station for the transmission of nociceptive information to the cerebral cortex, is activated by RF infusion. Electroacupuncture (EA) is an effective method for the treatment of pain. This study aimed to explore the role of VPL in the development of OIH and the effect of EA treatment on OIH in rats. RF was administered to rats via the tail vein for OIH induction. Paw withdrawal threshold (PWT) in response to mechanical stimuli and paw withdrawal latency (PWL) to thermal stimulation were tested in rats for the assessment of mechanical allodynia and thermal hyperalgesia, respectively. Spontaneous neuronal activity and local field potential (LFP) in VPL were recorded in freely moving rats using the in vivo multichannel recording technique. EA at 2 Hz frequency (pulse width 0.6 ms, 1–3 mA) was applied to the bilateral acupoints “Zusanli” (ST.36) and “Sanyinjiao” (SP.6) in rats. The results showed that both the PWT and PWL were significantly decreased after RF infusion to rats. Meanwhile, both the spontaneous neuronal firing rate and the theta band oscillation in VPL LFP were increased on day 3 post-RF infusion, indicating that the VPL may promote the development of RF-induced hyperalgesia by regulating the pain-related cortical activity. Moreover, 2 Hz-EA reversed the RF-induced decrease both in PWT and PWL of rats and also abrogated the RF-induced augmentation of the spontaneous neuronal activity and the power spectral density (PSD) of the theta band oscillation in VPL LFP. These results suggested that 2 Hz-EA attenuates the remifentanil-induced hyperalgesia via reducing the excitability of VPL neurons and the low-frequency (theta band) oscillation in VPL LFP.

Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats.

To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA) and mitogen-activated protein kinase (MEK) inhibitor on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal area CA1 of sham or chronic constrictive injury (CCI) rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor) group. In all experiments, we briefly (10-second duration) stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase) signaling pathway is involved in the modulation of EA analgesia.

Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance.

Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG). Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9). Mechanical withdraw threshold (MWT) was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P < 0.01). From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5). From M5 to M9, BME had the differences with BM group (P < 0.01). IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P < 0.01). Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

Effects of Chronic Electroacupuncture on Depression- and Anxiety-like Behaviors in Rats with Chronic Neuropathic Pain

Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints “Bai-Hui” (GV20) and unilateral “Yang-Ling-Quan” (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus.

The effects of electroacupuncture treatment on the postoperative cognitive function in aged rats with acute myocardial ischemia–reperfusion

Many literatures have proven that postoperative cognitive dysfunction (POCD) was very common in old patients after the injury of acute myocardial ischemia–reperfusion (AMIR) clinically such as the off-pump coronary artery bypass surgery (OPCAB) without definite mechanism; however, reports on the animal experiments were rarely seen. We hypothesized that AMIR could contribute to cognitive dysfunction, and this severe injury might be impeded by EA via hindering neuroinflammation and oxidative stress response as well as modulating the balance of the autonomic nervous system. The aged male Sprague Dawley rats were randomly assigned into three experimental groups: sham (sham operation), AMIR, and EA (electroacupunture treatment, acupoints GV20 and ST36+AMIR) groups. The survival rate, heart rate variability analysis, examination of pathology within the hippocampal CA1, oxidative stress, systemic inflammation and the behavior testing were evaluated by their corresponding methods. The results showed that the rats subjected to AMIR had lower survival rates, higher malondialdehyde (MDA), decreased superoxide dismutase (SOD) activity, more microglial activation, and presented evidence of severe brain injury and cognitive dysfunction on the 1st, 3rd, 7th days after reperfusion compared to sham-operated controls. Most important of all, the above damages induced by the AMIR were significantly improved by the EA treatment. Our findings indicated that EA treatment could be a neuroprotective therapy for the cognitive dysfunction induced by the AMIR event, which might be attributablefor balancing the autonomic nervous system, inhibiting the neuronic apoptosis, hindering microglial activation, attenuating oxidative stress and restraining the central and peripheral inflammation reactions.

Effect of ERK1/2 signaling pathway in electro-acupuncture mediated up-regulation of heme oxygenase-1 in lungs of rabbits with endotoxic shock.

BackgroundThe anti-oxidative and anti-inflammatory activities of electro-acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro-acupuncture – mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock.Material/MethodsSeventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1–5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-α, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein.ResultsThe results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-α levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all).ConclusionsAfter electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up-regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock.

Effect of electroacupuncture treatment on pain behavior and calcitonin-gene related peptide expression in cancer induced bone pain-morphine tolerance rat model

Objective To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP)-morphine tolerance rat model and the expression of calcitonin-gene related peptide(CGRP) immunohistochemisty in dorsal root ganglion (DRG). Methods Forty SD rats were divided into four groups: sham group, CIBP+ morphine tolerance group(BM), CIBP+ electroacupuncture group (BE), and CIBP+ morphine tolerance+ electroacupuncture group (BME). BM, BE and BME groups were prepared CIBP model by carcinoma cell tibia implanted.After six days, the three CIBP groups accepted treatment of morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days continuously. Acupoints were selected Zusanli(ST36) and Sanyinjiao(SP6). 50% mechanical withdraw threshold was evaluated by mechanical stimulation.CGRP expression in dorsal root ganglion was detected by immunohistochemisty. Results After five days of electroacupuncture treatment, pain threshold was (10.9±0.8)g in BME group, (8.7±0.6)g in BM group and (6.2±0.9)g in BE group.The results had significant statistic differences (P<0.01, separately). IOD value of CGRP expression in dorsal root ganglion was 9026.5±1827.4 in BME group, compared with 14803.1±2086.7 in BM group and 15730.6±2712.5 in BE group (P<0.01, separately). Results Electroacupuncture can relieve CIBP-morphine tolerance rat pain behavior. The mechanism is related to inhibiting CGRP overdue expression in DRG. Key words: Electroacupuncture; Cancer induced bone pain; Morphine tolerance; Calcitonin-gene related peptide

Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model.

BackgroundOpioid analgesics are generally used to combat the pain associated with cancerous conditions. These agents not only inhibit respiratory function and cause constipation, but also induce other significant side effects such as addiction and tolerance, all of which further contribute to a reduced quality of life for cancer patients. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in a cancer pain mouse model.MethodsIn order to produce a neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. Magnetic Resonance Imaging (MRI) scanning confirmed the mass of S-180 cancer cells embedded around the sciatic nerve. Mechanical allodynia was most consistently induced in the mouse sarcoma cell line S-180 (2 × 106sarcoma cells)-treated group compared to all the other groups studied. EA stimulation (2 Hz) was administered daily to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation.ResultsEA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation. It also shortened the cumulative lifting duration from 7 days after inoculation, compared to the tumor control. Also, the overexpression of pain peptide substance P in the dorsal horn of the spinal cord was significantly decreased in the EA-treated group compared to the tumor control on Day 9 post inoculation. Furthermore, EA treatment effectively increased the concentration of β-endorphin in blood and brain samples of the mice to a greater extent than that of the tumor control as well as the normal group. The concentration of β-endorphin for EA treatment group increased by 51.457% in the blood and 12.6% in the brain respectively, compared to the tumor control group.ConclusionThe findings of this study suggest that a S-180 cancer pain model is useful as a consistent and short time animal model. It also indicated that EA treatment could be used as an alternative therapeutic method for cancer pain due to a consequent decrease in substance P and increase in β-endorphin levels.