Electroacupuncture Research Articles

Electroacupuncture promotes gastrointestinal functional recovery after radical colorectal cancer surgery: a protocol of multicenter randomized controlled trial (CORRECT trial)

IntroductionThe incidence of postoperative gastrointestinal dysfunction (POGD) is notably high among patients following colorectal cancer surgery, highlighting the urgency for the prompt development of efficacious preventive and therapeutic approaches. Electroacupuncture (EA) represents an intervention modality that holds promise for the management of POGD. However, the existing empirical evidence substantiating its efficacy remains scarce. The aim of this study is to evaluate the efficacy and safety of EA as a treatment for POGD in patients undergoing colorectal cancer surgery.MethodsThis study is a multicenter, parallel-group, randomized controlled trial, named as CORRECT. CORRECT trial will recruit 300 participants diagnosed with colorectal cancer and about to undergo radical surgery across four sub-centers. The participants will be randomly assigned to one of three groups: the EA group, sham-electroacupuncture group, or control group, with a randomization ratio of 2:2:1. All groups will follow a standardized Enhanced Recovery After Surgery (ERAS) protocol. The EA group will receive EA at acupoints LI4, SJ6, ST36, and ST37, while the SA group will undergo sham-electroacupuncture. The treatments will be administered twice daily from the day of surgery until the fourth day after the operation. The primary endpoint is the time to first flatus, while secondary endpoints encompass time to first defecation, bowel sound emergence, initial water intake, duration of postoperative hospitalization, nausea and vomiting, pain levels, and blinded evaluations. Additional outcomes include medication usage and complication rates, et al.DiscussionThe CORRECT trial aims to provide high-quality evidence for the role of EA in the treatment of POGD following colorectal cancer surgery. It will contribute data towards the integration of acupuncture into ERAS protocols. Insights from the trial could help in tailoring treatment plans based on individual patient responses to EA, optimizing care on a case-by-case basis.Trial registrationClinical Trial Registry registration was approved by the ClinicalTrials.gov committee on November 2023 with the ClinicalTrials.gov Identifier: NCT06128785. URL: https://clinicaltrials.gov/study/NCT06128785?tab=history&a=1#study-details-card.

Electroacupuncture Mitigates TRPV1 Overexpression in the Central Nervous System Associated with Fibromyalgia in Mice

Background: Fibromyalgia (FM) is characterized by chronic pain, significantly affecting the quality of life and functional capabilities of patients. In addition to pain, patients may experience insomnia, chronic fatigue, depression, anxiety, and headaches, further complicating their overall well-being. The Transient Receptor Potential Vanilloid 1 (TRPV1) receptor responds to various noxious stimuli and plays a key role in regulating pain sensitivity and inflammation. Thus, targeting TRPV1 may provide analgesic and anti-inflammatory benefits. This study investigates the efficacy of electroacupuncture (EA) in alleviating chronic pain in FM through TRPV1 and its downstream molecules in the central nervous system (CNS). Methods: To model FM, we subjected mice to intermittent cold stress (ICS) for three days. The study comprised five rodent groups: Control (CON), ICS, ICS + EA, ICS + Sham EA, and ICS + KO (TRPV1 knockout mice). Results: Our findings revealed that ICS induced allodynia and hyperalgesia in mice by day four, persisting until day 21. EA at 2 Hz and TRPV1 KO significantly decreased both mechanical and thermal hypersensitivity (Withdrawal—Day 14: 2.43 ± 0.19 g; Day 21: 5.88 ± 0.47 g, n = 6, p < 0.05; Latency—Day 14: 2.77 ± 0.22 s; Day 21: 5.85 ± 0.41 s, n = 6, p < 0.05). In contrast, sham EA did not produce significant effects. Additionally, TRPV1 and several pain-related proteins were significantly elevated in the thalamus, somatosensory cortex (SSC), medial prefrontal cortex (mPFC), hippocampus, hypothalamus, cerebellum regions V (CB V), VI (CB VI) and VII (CB VII) after the ICS model. Both EA at the ST36 acupoint and TRPV1 KO mice showed diminished overexpression of pain-related proteins, with the sham EA group showing no significant changes compared to the ICS group. Conclusions: Chronic widespread pain was reduced by EA and TRPV1 KO, with the effects of EA on the TRPV1 pain pathway clearly evident in the CNS after 21 days.

Electroacupuncture for abdominal obesity: protocol for a systematic review and meta-analysis of randomised controlled trials

IntroductionThe prevalence of obesity is rising, significantly impacting health and quality of life. Effective treatment is crucial, particularly for abdominal obesity (AO). Electroacupuncture (EA), which combines acupuncture and moxibustion with...

Corticostriatal glutamate-mediated dynamic therapeutic efficacy of electroacupuncture in a parkinsonian rat model.

Motor impairments are the defining cardinal features of Parkinson's disease (PD), resulting from malfunction of the cortico-basal ganglia circuit. Clinical data have demonstrated that electroacupuncture (EA) stimulation may benefit motor symptoms in PD without adverse effects. However, the specific effects of EA on PD and the underlying mechanisms remain largely unclear. This study investigated the effects of EA stimulation during and after 100Hz application in a rat model of PD created by unilateral injection of 6-hydroxydopamine (6-OHDA). To establish optimal treatment parameters of EA, motor behaviours were dynamically assessed using open field and rotarod tests. Additionally, we evaluated corticostriatal spine plasticity using immunoelectron microscopy and measured the levels of dopaminergic and glutamatergic neurotransmitters through microdialysis, in vivo electrochemistry and high-performance liquid chromatography. Neural activity dynamics were recorded by measuring local field potentials in both the motor cortex and thestriatum. Furthermore, chemogenetic techniques were employed to manipulate corticostriatal glutamatergic neurons and clarify the mechanisms that contribute to the therapeutic benefits of EA in the PD rat model. Chronic EA stimulation resulted in a gradual and long-lasting alleviation of motor symptoms, independent of nigrostriatal dopamine (DA) restoration. Notably, EA stimulation modulated corticostriatal spine plasticity and reduced excessive glutamate transmission in PD model rats. Moreover, EA effectively inhibited aberrant corticostriatal synchronised high-beta (25-40Hz) oscillations, which serves as a pathological biomarker of PD. Conversely, chronic chemogenetic activation of corticostriatal glutamatergic neurons hindered these positive outcomes of EA treatment in PD model rats. This study sheds light on the temporal dynamics and optimal parameters of EA treatment in PD. It emphasises the significance of inhibiting corticostriatal glutamate transmission in EA's therapeutic benefits for PD. Targeting glutamatergic neurons with EA holds promise as a non-dopaminergic intervention for managing motor symptoms and abnormal neural activity with PD. EA commonly protects dopaminergic neuronsby reducing neuroinflammation, oxidative stress, and apoptosis. New findings reveal that EA alleviates motor symptoms in a parkinsonian rat model without restoring striatal dopamine levels. EA effectively suppresses excessiveglutamate transmission and high-beta synchronization, contributing to motorsymptom relief. Activation of corticostriatalglutamatergic projections may hinder the efficacy of EA.

Electroacupuncture Mechanisms in Managing Preoperative Anxiety and Postoperative Pain Chronification: A Review.

Postoperative hyperalgesic priming, exacerbated by preoperative anxiety, complicates pain management and recovery. Electroacupuncture (EA), a technique that combines traditional acupuncture with electrical stimulation applied through needles to enhance therapeutic effect, offers a potential solution by targeting multiple neurobiological pathways. This review investigates how EA addresses preoperative anxiety-induced postoperative hyperalgesic priming ie pain chronification, focusing on its mechanisms in three areas: preoperative anxiety, postoperative hyperalgesic priming, and the interaction between EA and these processes. A literature search across PubMed, ScienceDirect, and Google Scholar identified relevant studies on EA's effects on neurobiological pathways related to anxiety and pain. The review synthesized findings to understand EA's role in these contexts. EA alleviates preoperative anxiety by influencing the body's neurochemical and neurophysiological responses. It reduces inflammation, regulates stress hormones, and improves autonomic function. For postoperative pain chronification, EA modulates pain pathways, reduces inflammation, and affects receptor signaling, gene expression, and neurotransmitter systems. EA offers a promising approach to managing preoperative anxiety and postoperative pain. By addressing both the physiological and neurochemical pathways that contribute to pain and anxiety, EA has the potential to significantly improve clinical outcomes for patients undergoing surgery. Further research is needed to fully understand its mechanisms and optimize its application in clinical settings.

Impact of electro-acupuncture on EAAT2 and NMDAR-2B expression in goats with visceral hypersensitivity

ObjectiveThis study evaluates the effect of electro-acupuncture (EA) on visceral hypersensitivity (VH) and the expression of N-methyl-D-aspartate receptor-2B (NMDAR-2B) and glutamate transporter EAAT2 in goats. MethodsTwenty-four goats were divided into four groups: saline, 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS), TNBS + EA, and sham EA. EA was administered at Zusanli (ST36) with 60 Hz and 1–3 mA on specified days. Electromyography (EMG) recorded visceromotor response to colorectal distention (CRD). Spinal cords were collected for immunohistochemistry, western blotting, and RT-PCR. The ileum was examined histologically. ResultsThe repeated EA administration significantly attenuated VH (P < 0.05) in TNBS-treated goats without similar effects in the sham group. NMDAR-2B expression increased (P < 0.01), and EAAT2 expression decreased (P < 0.01) in the TNBS group compared to saline. EA increased the EAAT2 and decreased the NMDAR-2B expression (P < 0.01) compared to TNBS, with no change in the sham-EA group. ConclusionEA may alleviate VH by upregulating EAAT2 and downregulating NMDAR-2B in the spinal cord of TNBS-treated goats, indicating its potential for treating chronic visceral pain in gastrointestinal disorders.

A neural regulation mechanism of head electroacupuncture on brain network of patients with stroke related sleep disorders.

To analyze part of the mechanism of electroacupuncture on Sishencong (EX-HN1) for stroke-related sleep disorders (SSD) and post-stroke cognitive impairment (PSCI). Using a randomized controlled trial (RCT) design, 72 patients were assigned to the electro-acupuncture (EA) group or the sham acupuncture (SA) group. A healthy control (HC) group was also included. Both groups were given routine rehabilitation treatment. Then, patients in the EA group were given additional electroacupuncture at Sishencong (EX_HN1). Meanwhile, patients in the SA group were given a flat-head needle sham/placebo treatment placed at the bilateral Jianyu (LI15) and Binao (LI14) line midpoints and the Jianyu (LI15) and Jianzhen (SI9) line midpoints. Before and after treatment, scales were collected and analyzed. In the second phase of the study, some subjects from the EA group were selected for functional magnetic resonance imaging (fMRI) data acquisition and comparative analysis with the HC group using a non-RCT design. The EA group performed better than the SA group on the Pittsburgh sleep quality index (PSQI), Montreal cognitive assessment basic (MoCA_B), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Analysis of the fMRI showed that low-frequency (2 Hz) electroacupuncture stimulation at Sishencong (EX_HN1) can restrain frontal sup medial right (SFGmed.R), precuneus right (PCUN.R), and posterior cingulate cortex right (PCC.R) and enhance angular left (ANG.L), parietal inf left (IPL.L) and occipital mid left (MOG.L). The functional connectivity (FC) of SFGmed.R was positively correlated with PSQI. Electroacupuncture stimulation at Sishencong (EX_HN1) can reduce the side efficiency of the whole brain connection with the Thalamus.L, Hippocampus.L, and Occipital.Mid.L. Low frequency (2 Hz) electroacupuncture stimulation at Sishencong (EX_HN1) can simultaneously improve sleep quality, negative emotions, and cognitive functions, the first two of which may be related to SFGmed.R restraint. Electroacupuncture can make some brain areas approach the physiological bias state, which is characterized by dominant hemispheric enhancement and non-dominant hemispheric weakening. The reduced whole brain connection side efficiency with some key nodes of the brain net may relate to sleep quality improvements in SSD patients.

A spinal neural circuit for electroacupuncture that regulates gastric functional disorders

ObjectiveAcupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. MethodsA GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. ResultsEA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. ConclusionEA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders.

Electroacupuncture combined with NSCs-Exo alters the response of hippocampal neurons in a chronic unpredictable mild stress paradigm in ovx rats

Electroacupuncture (EA) is a form of Traditional Chinese Medicine (TCM) that combines acupuncture with microcurrents mimicking the body's bioelectricity to prevent and treat diseases. Previous studies have demonstrated its antidepressant-like effects in chronic unpredictable mild stress (CUMS)-induced ovariectomy (OVX) rats. Neural stem cell-derived exosomes (NSCs-Exo) are heterogeneous and targeted, effectively promoting nerve regeneration and repairing neuronal damage, while potentially conveying the effects of EA. However, the precise mechanism remains unclear. In this study, perimenopausal depressive disorder (PDD) rat model were established using a two-step protocol CUMS + OVX. Treatment with EA combined with NSCs-Exo (EA-Exo) significantly improved depression-like behaviors in PDD rats, as indicated by increased sucrose intake in the Sucrose Preference Test (SPT), reduced immobility in the Forced Swimming Test (FST), and prolonged activity in the Out-of-Field Test (OFT). EA-Exo treatment improved depression-like behaviors by increasing serum levels of 5-hydroxytryptamine (5-HT) and decreasing immobility in the FST. It also alleviated OVX-CUMS-induced disturbances in energy metabolism, inflammation, and oxidative stress responses by enhancing serum levels of 5-HT, dopamine (DA), ATP, superoxide dismutase (SOD), and interleukin-10 (IL-10), while reducing cyclic AMP (cAMP), interleukin-6 (IL-6), reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, EA-Exo treatment reversed structural and functional impairments in hippocampal synapses and mitochondria. This was evidenced by reductions in hippocampal synaptic plasticity proteins PSD95, SYN, and GAP43, as well as decreased expression of energy metabolism pathway proteins AMPK, NRF1, PGC1α, and TFAM. These findings suggest that EA-Exo ameliorates depressive behavior in OVX-CUMS rats by modulating synaptic plasticity and activating the AMPK/NRF1/PGC1α/TFAM signaling pathway.

Electroacupuncture with extensor exercise improves the contraction elastic density of quadriceps in short and long term for knee osteoarthritis.

Extensor training improves the quadriceps contraction intensity ofknee osteoarthritis. But the duration of effects is limited. This study aimed to assess whether electroacupuncture (EA) with extensor training (EA + E) has better short-and long-term effects than simple extensor training (E). Fifty-four patients were categorized into EA + E and E groups. Elastic shear wave imaging was employed to ascertain the quadriceps elastic modulus values (EMV) at different time points and extension angles. WOMAC scale was used to measure knee function. Compared to before EA, the vastus lateralis (VL) EMV with 180° knee extension immediately after EA increased significantly. After 1month, the vastus medialis (VM) EMV with 180° extension increased and WOMAC scores decreased significantly than immediately after EA. The EMV of the VM and VL of group EA + E increased, and WOMAC scores decreased significantly compared to group E after 1month. After 6months, EMV of the VM and VL in EA + E group significantly increased, and WOMAC scores significantly decreased compared to E group. In short- and long-term, EA with extensor training enhances the contraction strength of the quadriceps and knee function for OA. This prospective single-center randomized controlled trial was approved by the Review Committee of the First Affiliated Hospital of Sun Yat-sen University (Registration date: 28/02/2023, Ethical Number: [2023] 005; The Clinical trial registration number: ChiCTR2300076651. • The contraction strength of the quadriceps femoris muscle in OA was detected with shear wave elastic ultrasound, and electroacupuncture immediately enhanced the contraction strength. • After the completion of electroacupuncture treatment, the quadriceps strength and the function of knee joint in OA can be continuously improved, which will last for 6months. • In short and long term, electroacupuncture with extensor training has better enhancement of quadriceps contraction strength of and knee function for OA than extention only.

Effect of "Xingshen-Jieyu" electroacupuncture on serum differential metabolites in patients with depression based on metabolomics

To explore the effect of "Xingshen-Jieyu" (inducing resuscitation and dispel ling melancholy) electroacupuncture (EA) on serum metabolites in patients with depression and its underlying mechanisms through serum non-targeted metabolomics. Fifteen depression patients were subjected into the EA group, and 15 healthy volunteers were matched into the healthy group. EA (2 Hz/15 Hz, a tolerable strength) was applied to Baihui (GV20), Shenting (GV24), Toulinqi (GB15), Benshen (GB13), Touwei (ST8), Xuanli (GB6) and Qubin (GB7) for 30 min, 3 times a week for 6 weeks. The severity of depression was assessed using Hamilton Depression Scale-17 (HAMD-17) and Hamilton Anxiety Scale (HAMA), the degree of fatigue was evaluated using Fatigue Scale-14 (FS-14). The subjects sleep quality was assessed using Pittsburgh sleep quality index (PSQI). Blood samples were collected before and after the treatment for processing serum to perform non-targeted metabolomics profile detection using ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), and Partial Least Squares Discriminant Analysis (PLS-DA, a statistical approach). Differential metabolites were screened and pathway enrichment analysis was performed. After the treatment, the scores of HAMD-17, HAMA, PSQI and FS-14 of depression patients were significantly lowered in the EA group (P<0.05). Compared with the healthy subjects, 46 differential metabolites (21 up-regulated, 25 down-regulated) were screened in patients with depression. Compared with pre-treatment in the EA group, 19 differential (17 up-regulated, and 2 down-regulated) metabolites were screened. Four down-regulated metabolites of the 46 differential metabolites in depression patients were recovered after EA treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differential metabolites before and after EA showed that 19 metabolic pathways were enriched, mainly involving glutaminergic synapses, GABAergic synapses and several amino acid metabolism related pathways. "Xingshen-Jieyu" EA mainly regulates the metabolism of amino acids, and activities of neurotransmitter glutamate and GABA, and restores the excitatory/inhibitory balance, thus playing a role in improving depression.

Effect of electroacupuncture on synaptic ultrastructure and synaptic function related proteins PSD95 and MeCP2 in sleep deprivation rats

To observe the effect of electroacupuncture (EA) on the expression of synaptic function related proteins PSD95 and MeCP2 and synaptic ultrastructure in sleep deprived rats, so as to explore its mechanism underlying improvement of learning and memory ability caused by sleep deprivation. SD rats were randomly divided into normal, model, EA and sham EA groups (n=10). The sleep deprivation model was prepared by modified multi-platform water environment. Rats of the EA group received EA stimulation at "Baihui" (GV20) and "Dazhui" (GV14), while the sham EA group received shallow needling 4 mm away from the above acupoints without electrical stimulation. The learning and memory ability was evaluated with Morris water maze test. The density of dendritic spines in hippocampal CA1 region was detected by Golgi staining. The synaptic ultrastructure of hippocampus was observed by electron microscope. The protein expression levels of PSD95 and MeCP2 in hippocampus was detected by Western blot. Compared with the normal group, the escaping latency of the positioning navigation experiment in the model group was prolonged (P<0.05), the number of crossing the platform and the residence time in the target quadrant were decreased(P<0.05), the density of dendritic spines in the hippocampal CA1 area was decreased (P<0.05), the number of synapses was reduced, with swollen synaptosomes, blurred synaptic structure, disappeared and narrowed synaptic clefts, the protein expression levels of PSD95 and MeCP2 were significantly decreased (P<0.05) in the model group. Compared with the model group, the escape latency of the positioning navigation experiment was shortened (P<0.05), the number of crossing platforms and the time spent in the target quadrant were increased (P<0.05), the density of dendritic spines in the hippocampal CA1 region was increased (P<0.05), the morphology of synaptic improved, the protein expression levels of PSD95 and MeCP2 were increased (P<0.01) in the EA and sham EA groups. The improvement of the above indexes in EA group was more obvious than those in sham EA group. EA can improve the learning and memory of sleep deprivation rats, which may be related to its function in regulating the expressions of synaptic related proteins PSD95 and MeCP2, and improving the synaptic structure.

Electroacupuncture reduces neuronal apoptosis in rats with spinal cord injury by regulating GSK-3β expression and its phosphorylation

To observe the effect of electroacupuncture (EA) stimulation of "Dazhui"(GV14) and "Mingmen" (GV4) of the Governor Vessel (GV) on the apoptosis of neurons in rats with spinal cord injury (SCI) by regulating the expression of glycogen synthase kinase-3β (GSK-3β) protein and its phosphorylation level, so as to reveal partial mechanism for the treatment of SCI with EA of GV. A total of 45 male SD rats were randomly divided into sham-operation, model and EA groups, 15 rats in each group. The SCI model was established by using the modified Allen's percussion device. EA stimulation (2 Hz, 1 mA) was applied to GV14 and GV4 for 20 min, once daily for 28 days. Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the rat's hind limb motor function at the 1st, 7th, 14th, 21th and 28th day after modeling. H.E. staining was used to observe the histopathological changes of the injured spinal cord tissue. The expressions of GSK-3β and its phosphorylation at Ser9 site in the spinal cord were detected by immunohistochemistry and Western blot, respectively. The TUNEL staining was used to observe the apoptosis of neuron in the spinal cord. In comparison with the control group, the BBB scores from day 1 to day 28, and the expression and immunoactivity of p-GSK-3β were significantly decreased (P<0.01), while the expression and immunoactivity of GSK-3β and the apoptosis index were significantly increased (P<0.01) in the model group. In contrast to the model group, the EA group had a remarkable increase in the BBB score from day 7 to day 28, and the expression and immunoactivity of p-GSK-3β (P<0.05, P<0.01), and an obvious decrease (P<0.05, P<0.01) in the expression and immunoactivity of GSK-3β and the apoptosis index. H.E. staining showed that in the model group, the spinal cord structure of the SCI region was disorganized, with tissue cavity, blurred gray matter boundary, severe inflammatory infiltration, reduction of normal neurons, loss of cytoplasm, and nuclear contraction, which was relatively milder in the EA group. EA at GV14 and GV4 can improve the symptoms of neurological function injury and reduce the apoptosis of neurons in rats with SCI, which may be achieved by regulating GSK-3β protein and its phosphorylation level.

Effects of electroacupuncture at auricular points on excitability of glutamatergic neurons in the anterior cingulate cortex of posttraumatic stress disorder mice

To elucidate the relationship between the auricular point stimulation and the activity of glutamatergic neurons in the anterior cingulate cortex (ACC) from the perspective of intrinsic excitability plasticity of neurons in mice with posttraumatic stress disorder (PTSD), so as to explore the underlying mechanisms of acupuncture at auricular points in improving emotional diseases induced by PTSD. C57BL/6J male mice were randomly divided into control, PTSD model, sham electroacupuncture (EA), and EA groups, with 5 mice in each group. The glutamatergic neurons were labelled by injection of AAV2/9-CaMKⅡα-EGFP viral fluid into the bilateral ACC. Fourteen days after the injection, the PTSD model was established by single prolonged stress (restraint stress, forced swimming, ether exposure) and plantar electrical shock. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Xin" points and the center of auriculae of auricular concha area for 30 min, once daily for 7 days. Mice of the sham EA group were anesthetized for 30 min per day for 7 days, but no EA treatments were given. The anxiety-like behavior of mice was evaluated by open field (OF) and elevated plus maze (EPM) tests after 2 weeks of modeling. The whole-cell patch-clamp method was used to record the intrinsic excitability level of ACC glutamatergic neurons. Compared with the control group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM in the model group were significantly reduced (P<0.001, P<0.01). At the same time, the intrinsic excitability of ACC glutamatergic neurons in model mice was suppressed, presenting as enhanced rheobase currents (P<0.01) and decreased spike number (P<0.05, P<0.01, P<0.001). Compared with the model group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the elevated plus maze were significantly increased (P<0.001, P<0.01), and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents (P<0.05) and an increased spike number (P<0.05) in the EA group. Compared with the sham EA group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM were significantly increased (P<0.001, P<0.01) in the EA group, and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents (P<0.01) and an increased spike number (P<0.05). EA of auricular points can effectively alleviate the anxiety-like behavior of PTSD mice and increase the intrinsic excitability level of glutamatergic neurons in ACC, which may be one of the neural mechanisms of auricular point stimulation in the treatment of emotional diseases.

Electroacupuncture Serum Protects Blood-brain Barrier Damage after Ischemic Stroke BY Regulating the Pericytes in vitro.

Electroacupuncture (EA) exerts a protective role in Blood-Brain Barrier (BBB) damage after ischemic stroke, but whether this effect involves the regulation of the pericytes in vitro is unclear. The in vitro BBB models were established with brain microvascular endothelial cells (BMECs) and pericytes, and the co-cultured cells were randomly divided into three groups: the control group, oxygen-glucose deprivation/reoxygenation (OGD/R) group and EA group. OGD/R was performed to simulate cerebral ischemia-reperfusion in vitro. EA serum was prepared by EA treatment at the "Renzhong" (GV26) and "Baihui" (GV20) acupoints in middle cerebral artery occlusion/ reperfusion rats. Furthermore, the characteristics of BMECs and pericytes were identified with immunohistochemistry staining. The cell morphology of the BBB model was observed using an inverted microscope. The function of BBB was measured with transendothelial electrical resistance (TEER) and sodium fluorescein, and the viability, apoptosis, and migration of pericytes were detected by cell counting kit-8, flow cytometry, and Transwell migration assay. BMECs were positive staining for Factor-VIII, and pericytes were positive staining for the α-SMA and NG2. EA serum improved cell morphology of the BBB model increased TEER, and decreased sodium fluorescein in OGD/R condition. Besides, EA serum alleviated pericytes" apoptosis rate and migration number, and enhanced pericytes' viability rate in OGD/R condition. EA serum protects against BBB damage induced by OGD/R in vitro, and this protection might be achieved by attenuating pericytes apoptosis and migration, as well as enhancing pericytes viability. The findings provided new evidence for EA as a medical therapy for ischemic stroke.

Effects of electroacupuncture on expression of miR-218 and HMGB1/TLR4 signaling pathway in rats with focal cerebral ischemia

To observe the effect of electroacupuncture (EA) on high mobility group box 1 (HMGB1) / toll-like receptor 4 (TLR4) signaling pathway and inflammatory injury in rats with focal cerebral ischemia (FCI), so as to explore its mechanisms underlying amelioration of ischemic stroke. Male SD rats were randomly divided into sham operation (n=18), model (n=18) and EA (n=18) groups. The FCI model was established according to Longa's method. In the EA group, 24 h after modeling, EA stimulation was applied to "Baihui"(GV20), "Fengfu"(GV16), and "Neiguan" (PC6) and "Xinshu" (BL15) on the left side for 20 min, once a day for 1 week. The neurological deficit severity was evaluated by the modified neurological severity score (mNSS), and the morphological changes of neurons were observed after H.E. staining. The expression of HMGB1 and TLR4 proteins were detected by immunofluorescence staining. The contents of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in the ischemic area tissue of the brain were detected using ELISA. The mRNA expressions of HMGB1 and TLR4 as well as the expression of miR-218 in the ischemic cortex were detected by PCR. Compared with the sham operation group, the mNSS at 2 h, 48 h and 7 day (d), IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 48 h and 7 d were significantly increased (P<0.01), while miR-218 expression at 48 h and 7 d was obviously down-regulated (P<0.01) in the model group. In comparison with the model group, the mNSS at 7 d, IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 7 d not at 48 h were significantly decreased (P<0.01, P<0.05), while the expression of miR-218 at 7 d was apparently up-regulated (P<0.05) in the EA group. H.E. staining showed that there were signs of neuronal necrosis including blurred outline of the cells, disordered internal structure, dense cytoplasm, shrunk nuclei, etc. in the ischemic area of the brain at 48 h and 7 d in the model group, which was evidently milder on day 7 in the EA group. EA can reduce the inflammatory injury of brain tissue and improve the neurological impairment in rats with FCI, which may be associated with its effects in inhibiting HMGB1/TLR4 signaling and down-regulating the level of pro-inflammatory cytokines.

Effect of electroacupuncture on the characteristic signal of electroencephalogram in the patients with chronic insomnia： a randomized controlled trial

To observe the effect of electroacupuncture (EA) on sleep quality and electroencephalogram (EEG) signal in the patients with chronic insomnia and to explore its mechanism. Sixty patients with chronic insomnia were randomized into an EA group (30 cases, 3 cases dropped out) and a health learning group (30 cases, 3 cases dropped out). In the health learning group, the sleep health education was provided. In the EA group, besides the health education as the health learning group, EA was delivered at Baihui (GV20), Yintang (GV24+), bilateral Shenmen (HT7), bilateral Sanyinjiao (SP6), with continuous wave, 2 Hz in frequency, once every other day, and 3 interventions a week. EA was given for 4 weeks successi-vely, composed of 12 treatments. The score of Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), and patient health questionnaire-9 (PHQ-9) before and after treatment were compared between the two groups. The EEG signals were collected and the relative power and entropy of EEG before and after treatment were compared between the two groups. After treatment, the scores of PSQI, HAMA and PHQ-9, the relevant power of β wave in F8 and T3 channels, and that of α wave in T4 channel, and the entropy in T3 channel under the eyes-open (EO) resting state, as well as the relevant power and the entropy of γ wave in F8 channel under the eyes-closed (EC) resting state in the EA group were lower (P<0.05) than those before the treatment. All of the above results were lower than those of the health learning group at the same time points (P<0.05). Under the EO resting state, the relevant power of the θ and δ waves of T3 channel and θ wave of T4, O2 and Pz channels of patients in the EA group after the treatment were increased (P<0.05) than those before the treatment, and higher (P<0.05) than those of the health learning group at the same time points. Acupuncture is effective on chronic insomnia, which may be related to the regulation EEG signals.

Electroacupuncture of "Jiaji" (EX-B2) inhibits inflammatory response by regulating HMGB1/TLR4/NF-κB signaling pathway in rats with spinal cord injury

To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B2) on expression of high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) related proteins and inflammation-related factors in spinal cord injury (SCI) rats, so as to explore the dynamic process of inhibiting inflammatory response in rats with SCI, and to provide a new idea and theoretical basis of molecular biology for the treatment of SCI. Fifty-four SD rats were randomly divided into sham operation, model, and EA groups (n=18 in each group), which were further divided into 3 d, 7 d and 14 d subgroups, with 6 rats at each time point. The SCI model was established according to the Allen's method. Rats in EA group received EA (1 mA, 100 Hz) intervention at EX-B2 of T9 and T11 24 hours after modeling for 30 min, once a day for 3 d, 7 d, or 14 d, respectively. The motor function of rats' hind limbs was evaluated using BBB scale, the morphological structure of rats' spinal cord tissue was observed by H.E. staining. The contents of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in spinal cord tissue were detected by ELISA. Western blot and immunofluorescence staining were used to detect the relative protein expression and fluorescence positive expression of HMGB1, TLR4 and NF-κB p65 in spinal cord tissue, respectively. Compared with the sham operation group, the BBB scores after modeling and on day 3, 7 and 14 were all decreased (P<0.05), while the contents of iNOS and COX-2 in spinal cord tissue, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were increased (P<0.05) in the model group. In comparison with the model group, the BBB scores on day 3, 7 and 14 were obviously increased (P<0.05), while the contents of iNOS and COX-2, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were significantly down-regulated in the EA group (P<0.05). EA of "Jiaji" can promote the recovery of SCI neurological function, which may be related to its function in regulating the HMGB1/TLR4/NF-κB signaling pathway, down-regulating the expression of iNOS and COX-2, and inhibiting the neuroinflammatory response after SCI.

High-intensity electroacupuncture is superior to low-intensity electroacupuncture for knee osteoarthritis: a meta-analysis of randomized controlled trials.

Electroacupuncture (EA) has been demonstrated to be efficacious and safe in patients with knee osteoarthritis (KOA), yet the optimal current intensity for pain control in KOA remains unspecified. The present meta-analysis aimed to compare the effects of high-intensity and low-intensity EA in terms of pain relief and functional improvement in KOA. A thorough and comprehensive literature search for randomized controlled trials (RCTs), all looking at the intensity of EA for KOA, was carried out in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science Journal Citation Report (VIP) and Wanfang database, as well as ClinicalTrials.gov. All databases were searched from their inception until April 2022. Study quality was assessed using the Cochrane risk of bias (RoB)2 tool. Finally, a meta-analysis of all eligible RCTs was performed using Review Manager 5.3. Three studies with 472 individuals were included in the meta-analysis. The pain intensity reductions were significantly different between the high-intensity EA group and low-intensity EA group (mean difference (MD) = -0.22, 95% confidence interval (CI) = -0.26 to -0.18, p < 0.00001). There was no significant difference between the two groups in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (MD = -3.62, 95% CI = -12.22 to 4.98, p = 0.41). High-intensity EA significantly improved emotional scale (ES) scores compared to low-intensity EA (MD = -0.72, 95% CI = -0.76 to -0.67, p < 0.00001). The findings of this systematic review and meta-analysis indicated that high-intensity EA provides superior pain relief and has a bigger impact on emotional scale scores in patients with KOA.

Electroacupuncture improves V1 cortex synaptic plasticity via the CREB/BDNF/TrkB pathway in juvenile rats with monocular deprivation

The present study aims to investigate the impact of the CREB/BDNF/TrkB signaling pathway on synaptic plasticity in the visual cortex of juvenile amblyopic rats that have undergone monocular deprivation (MD). This study involved sixty 2-week-old Sprague-Dawley (SD) juvenile rats, which were not specified by gender. In the first part of the study, 24 rats were randomized into control and MD groups; In the second part, 36 rats were randomized into MD, electroacupuncture (EA) and EA + CREB antagonist (666–15) groups. The MD model was established using the monocular suture method. 14 d after monocular suture, EA treatment was started for 30 min daily, at a frequency of 2–10 Hz and an intensity of 1 mA, for 2 weeks. According to the results from part 1, the P100 wave latency in the MD group was prolonged, and its amplitude was lower compared to the control group. Additionally, the neuron number in the V1 cortex of the MD group decreased, along with reduced expression levels of CREB, BDNF, p-TrkB, and the key plasticity proteins PSD95 and SYN. In part 2, EA treatment significantly increased the electrophysiological activity of neurons in V1 cortex, shortened the latency of P100 peaks to varying degrees, increased the amplitude significantly, and restored the morphology and structure of neurons to normal levels; The expression of synaptic proteins PSD95 and SYN, as well as the expression of signaling molecules CREB, BDNF, and p-TrkB proteins were increased. However, the effects of EA were reversed when the specific CREB inhibitor 666–16 was administered. These data indicate that EA enhances the expression of V1 cortical synaptic plasticity-related proteins by regulating the expression of CREB/BDNF/TrkB signaling pathway, thereby enhancing V1 neural synaptic plasticity and reversing the effects of MD on visual acuity.