Electroacupuncture Stimulation Research Articles

Clinical observation of electroacupuncture with different frequencies for migraine without aura

To observe the clinical efficacy of electroacupuncture (EA) with different frequencies in treating migraine. Ninety patients with migraine were divided into a low frequency electroacupuncture (LF-EA) group, a high frequency electroacupuncture (HF-EA) group and a variable frequency electroacupuncture (VF-EA) group by the random number table method. Shuaigu (GB 8), Hegu (LI 4), Waiguan (TE 5), Taichong (LR 3), Taiyang (EX-HN 5), Fengchi (GB 20) and Ashi points were selected for all three groups. After achieving needling sensation (Deqi), the LF-EA group received 2 Hz continuous wave EA stimulation; the HF-EA group received 100 Hz continuous wave EA stimulation, and the VF-EA group received 2 Hz/100 Hz sparse-dense wave EA stimulation. The EA stimulation lasted for 30 min in all the three groups, once a day, 10 times as a course, and the clinical efficacy was evaluated after 2 consecutive courses of treatment. After treatment, the total effective rates in the LF-EA group, HF-EA group and VF-EA group were 77.7%, 83.3% and 93.3%, respectively. The difference in total effective rate between the LF-EA and HF-EA groups was not statistically significant (P>0.05), but the total effective rate was significantly higher in the VF-EA group than in the LF-EA and HF-EA groups (both P 0.05), while the score was significantly lower in the VF-EA group than in the LF-EA and HF-EA groups (both P<0.01). VF-EA (2 Hz/100 Hz), compared with LF-EA (2 Hz) and HF-EA (100 Hz), shows superior clinical efficacy in treating migraine.

Electroacupuncture stimulation at BL20, BL23 and SP6 prevents hind limb unloading-induced osteoporosis in rats.

Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at -30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

Electroacupuncture Attenuates Ischemic Brain Injury and Cellular Apoptosis via Mitochondrial Translocation of Cofilin.

To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke. The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot. Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01). EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.

Electroacupuncture Enhance Therapeutic Efficacy of Mesenchymal Stem Cells Transplantation in Rats With Intracerebral Hemorrhage.

Previous studies have showed the beneficial effects of mesenchymal stem cells (MSCs) on experimental intracerebral hemorrhage (ICH) animal. Enhancement of the treatment efficacy of MSCs in ICH is essential, considering the diseases association with high rates of disability and mortality. Some auxiliary methods to enhance the beneficial efficacy of MSCs have been introduced. However, the effect of electroacupuncture (EA) on the therapeutic efficacy of MSCs transplantation in hemorrhagic stroke and its potential mechanism is not explored. ICH rat models were established using collagenase and heparin. 48h after ICH induction, the rats were randomly divided into model control (MC), MSCs transplantation (MSCs), EA stimulation (EA) and MSCs transplantation combined with EA stimulation (MSCs + EA) groups. We used mNSS test and gait analysis to assess neurological function of rats, and PET/CT to evaluate the volume of hemorrhage focus and level of glucose uptake. The concentrations of MDA, SOD, NSE, S100B and MBP in serum or plasma were examined with ELISA. Neural differentiation of MSCs, and the expressions of Bcl-2, Bax, Arg-1 and iNOS proteins around hematoma were detected by immunofluorescence and immunohistochemistry staining respectively. Western blot was carried out to analyze the expression levels of COX4, OGDH, PDH-E1α, Bcl-2 and Bax proteins. TUNEL staining was used to estimate cell apoptosis and transmission electron microscopy (TEM) was used to observe the ultrastructure and number of mitochondria. Our data showed that EA promoted neuron-like differentiation of transplanted MSCs and the expressions of BDNF and NGF proteins in ICH rats. The score of mNSS and the gait analysis showed that the recovery of the neurological function in the MSCs + EA group was better than that in the MSCs and EA groups. EA improved the structure of brain tissue, and alleviated brain injury further after MSCs transplantation in ICH rats. When compared with the MSCs and EA groups, the level of glucose uptake and numbers of mitochondria and Arg-1 positive cells in MSCs + EA group increased significantly, but the numbers of apoptotic cells and iNOS positive cells and volume of hemorrhage focus reduced. The expressional levels of COX4, OGDH, PDH-E1α and Bcl-2 proteins increased, while the expressional level of Bax protein decreased compared with those in the MSCs and EA groups. Our results reveal that EA improve therapeutic efficacy of MSCs transplantation in ICH rats.

The Instant and Sustained Effect of Electroacupuncture in Postgraduate Students with Depression: An fMRI Study.

ObjectionThis study was a primary study to evaluate the instant and sustained effect of electroacupuncture (EA) at GV20 (Baihui) in postgraduate students with mild depression by using a special flexible head coil.MethodsA total of 20 postgraduate students with mild depression underwent EA stimulation at GV20 and 3 phases of resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Phase I: Preparation (before needle insertion); Phase II: during EA; Phase III: 15 minutes after needle removal. The Rs-fMRI data were processed using DPABI and SPSS 25.Results1) ReHo values showed significantly differences in the right posterior cingulate cortex, right calcarine gyrus, right angular gyrus, right precuneus, right cuneus, and bilateral postcentral gyri among Phase I, Phase II and Phase III; 2) Relative to the Phase I, increased brain activity in the Phase II was observed in the bilateral postcentral gyri, right calcarine gyrus, right cuneus. Compared with the Phase II, decreased brain activity in the Phase III was observed in the right precuneus, right posterior cingulate cortex, right angular gyrus. Relative to the Phase I, Significantly increased brain activity in the Phase III was observed in the right calcarine gyrus, right cuneus, and bilateral postcentral gyri. While decreased ReHo values were found in the right posterior cingulate cortex, right angular gyrus, right precuneus; and 3) Correlation analysis showed that the ReHo values of multiple brain regions in Phase I and Phase III were significantly correlated with the VAS and HRSD-17 scores.ConclusionThis study focuses on the instant and sustained effect in postgraduate students with depression. Our study showed that instant effect produced by EA stimulation at GV20 firstly induced changes in somatosensory and visual area, and then, sustained effect (Phase III) have a higher intensity and more extensive than instant effects. Meanwhile, we provide a visualization way to study the instant effects of head acupoints by using a flexible head coil.

The effectiveness of electro-acupuncture combined with dyclonine hydrochloride in relieving the side effects of gastroscopy: a controlled trial.

The present study aimed to explore the effectiveness of electro-acupuncture (EA) in combination with a local anesthetic used in Western medicine in preventing the side effects of gastroscopy. A sample group of 150 patients were divided into three groups based on treatment methods: an EA group, a dyclonine hydrochloride mucilage group, and a combined treatment group. In the EA group, EA stimulation was given at the Hegu, Neiguan, and Zusanli acupoints; in the dyclonine hydrochloride mucilage group, patients took 10 mL of dyclonine hydrochloride mucilage orally; in the combined treatment group, prevention of side effects was attempted by administration of both acupuncture and oral local anesthetic. The incidences of nausea, emesis, salivation, cough, restlessness, and breath holding during gastroscopy were observed and recorded for the three groups. Mean arterial pressure, heart rate, and oxygen saturation were recorded before the examination, and changes in these measures were recorded as the gastroscope passed through the pylorus and after the examination. The visual analogue scale (VAS) values of nausea and emesis, the rate of successful first-pass intubation, and the time of gastroscopy were also recorded. Statistical analysis was performed using R-3.5.3 software. Incidences of side effects (e.g., nausea, emesis, salivation, restlessness, and breath holding) during the examination were lower in the combined treatment group than in the EA group and the dyclonine hydrochloride mucilage group (P<0.05 and P<0.01, respectively). Furthermore, the changes in heart rate and oxygen saturation when the gastroscope passed through the pylorus and after the examination were better in the combined treatment group than in the EA group and dyclonine hydrochloride mucilage group (P<0.01). The VAS values of nausea and emesis, the first-pass success rate, and examination duration were also better for the combined treatment group than for the other two groups (P<0.05 and P<0.01). EA combined with local anesthesia with dyclonine hydrochloride mucilage can alleviate side effects during gastroscopy, reduce patient pain, and improve the efficiency of the procedure.

Lipid Profile Response to Electroacupuncture in Non-Alcoholic Fatty Liver Patients with Hyperlipidemia.

Non-alcoholic fatty liver disease (NAFLD) is estimated to be one of the most common diseases affecting the liver because of its high prevalence worldwide. Abnormal lipid profile between NAFLD patients has been reported in several studies. This study aimed to evaluate the lipid profile response to electroacupuncture in NAFLD patients. A total of 60 female patients with NAFLD were included in the study with ages ranged from (30-55) years old. They were divided equally into two groups, group A received electroacupuncture (EA) stimulation at points of; LR14, LR3, ST36, and GB34. And group B received sham acupuncture application in non-acupuncture points. The demographic data and lipid profile such as total cholesterol (TC), serum triglycerides (TG), serum high-density lipoprotein (HDL), serum low-density lipoprotein (LDL) were recorded before and after the study. The study results revealed a significant decrease (p < 0.05) of LDL, TC, TG after 6 weeks of non-interrupted treatment sessions in group A, However HDL showed no significant improvement (p > 0.05). A significant difference was found between posttreatment values of LDL, TC, and TG between both groups. Electroacupuncture can be an effective, simple, and applicable method for the improvement of elevated lipid profiles in NAFLD patients.

Effect of electroacupuncture pretreatment on the protein expression of c-fos in fastigial nucleus and lateral hypothalamus area in rats with acute myocardial ischemia-reperfusion injury

To observe the effect of electroacupuncture (EA) pretreatment on the protein expression of c-fos in fastigial nucleus (FN) and lateral hypothalamus area (LHA) in rats with acute myocardial ischemia-reperfusion injury (MIRI), and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction. Seventy Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an EA-Heart Meridian group and an EA-Lung Meridian group, with 14 rats in each group; an LHA lesion plus EA-Heart Meridian group (LHA+EA-Heart Meridian group) and a FN lesion plus EA-Heart Meridian group (FN+EA-Heart Meridian group), with 7 rats in each group. Except the sham operation group, the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups. In the three groups with EA-Heart Meridian treatment, Shenmen (HT 7) and Tongli (HT 5) were selected; Taiyuan (LU 9) and Lieque (LU 7) were selected in the EA-Lung Meridian group. All the EA groups received EA stimulation prior to modeling, with 1 mA in current intensity and 2 Hz in frequency, 20 min each time, once a day for a total of 7 d. The sham operation group and the model group did not receive EA stimulation. The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score. The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method. Compared with the sham operation group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group (all P<0.05). Compared with the model group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group (all P<0.05). Compared with the EA-Heart Meridian group, the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group, LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group (all P<0.05); the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group (both P<0.05); the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group (both P<0.05). FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions, and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

Effect of electroacupuncture of Taichong (LR3) on somatosensory evoked cortical potentials in healthy volunteers

To explore the excitatory effect of the sensory cortex through somatic electroacupuncture (EA) stimulation at Taichong (LR3). Ten healthy volunteer men ranging in age from 20 to 50 years were enrolled in this study. EA (2 Hz, a tolerable strength) was applied to the left LR3. Before and after EA, the somatosensory evoked potential (SEP) from the Cz' area of the scalp was recorded by electrical stimulation of the bilateral dorsal penile nerves and the indentation behind the medial malleolus of the foot, termed as the pudendal SEP (PSEP) and lower extremity SEP (LSEP), respectively. The amplitude of the left LSEP induced by stimulation of the left medial malleolus was significantly increased after EA (P < 0.05), but there were no significant changes in the latency of LSEP and PSEP, and the amplitude of right LSEP evoked by stimulation of the left medial malleolus, and that of the PSEP. EA at LR3 increases the excitability of the contralateral cerebral sensory cortex (lower extremity area), but has no effect on the adjacent sensory cortex (genital area).

Acupoint sensitization enhances inhibitory effect of electroacupuncture on jejunum mobility in rats

To observe the effect difference of electroacupuncture (EA) at the sensitized and non-sensitized acupoint "Tianshu" (ST25) on the motility of jejunum in rats. Male SD rats were randomly divided into blank control, sensitized ST25 (sensitization), and non-sensitized ST25 (non-sensitization) groups (n=16 in each group). The sensitization and non-sensitization were induced by injection of 15% mustard oil (20 μL) and Paraffin oil (20 μL) into the left ST25 area respectively. The rats' behavior reactions were assessed by recording the numbers and duration of licking the local sensitized skin region. At the end of experiments and after regular trans-cardiac perfusion and fixing with 10% neutral formaldehyde, the skin and muscular tissues of the ST25 region (1 cm×1 cm) were taken for H.E. staining to observe the local histopathologic changes. The intestinal motility was detected by recording the contraction pressure waves of jejunum through a small balloon-connected pressure transducer and an amplifier, followed by calculating the ratios of amplitude and frequency of contraction waves between pre- and post-EA stimulation. EA (2 Hz, 0.2-6.0 mA) was applied to the sensitized and non-sensitized ST25 regions for 20 s for comparing their effects on jejunum motility. Compared with the blank control group, mustard oil injection but not Paraffin oil injection resulted in histological edema and neutrophils infiltration in tissues of ST25 region, and also striking increase of the number and duration of licking (P<0.01), suggesting a sensitization of ST25 area after mustard oil injection. The ratios of spontaneous contraction amplitude and frequency of jejunum were remarkably decreased in mustard oil-treated rats compared to baseline and Paraffin oil group (P<0.001，P<0.01). The maximum inhibitory effect of EA on the intestinal movement amplitude was significantly higher in the sensitization group than in the blank control and non-sensitization groups (P<0.05，P<0.01), and there was a dose-effect relationship between the current intensity of EA (0.5-3.0 mA) and the inhibitory rate 50% of the contraction amplitude (not the frequency) in the sensitization group (P<0.001), but not in the blank control and non-sensitization groups (P>0.05). Additionally, 1.5 mA EA stimulation at the sensitized ST25 (not at the non-sensitized ST25) had an inhibitory effect on the contraction amplitude (P<0.05) rather than on the contraction frequency (P>0.05) in comparison with the blank control group. Sensitization of acupoint ST25 can modulate the motility of jejunum and enhances the inhibitory effect of EA on the contraction amplitude of jejunum in rats. The inhibitory effect of sensitized ST25 EA is evidently stronger than that of the non-sensitized ST25 EA.

Electroacupuncture Ameliorates Neuroinflammation-Mediated Cognitive Deficits through Inhibition of NLRP3 in Presenilin1/2 Conditional Double Knockout Mice.

Neuroinflammation is considered as one of the crucial pathogenesis in promoting neurodegenerative progress of Alzheimer's disease (AD). As complementary and alternative therapy, electroacupuncture (EA) stimulation has been widely used in clinical practice for anti-inflammation. However, whether EA promotes the cognitive deficits resulting from neuroinflammation in AD remains unclear. In this study, the presenilin 1 and 2 conditional double knockout (PS cDKO) mice, exhibited a series of AD-like pathology, robust neuroinflammatory responses, and memory deficits, were used to evaluate the potential neuroprotective effect of EA at Baihui (GV 20) and Shenting (GV 24) by behavioral testing, electrophysiology recording, and molecular biology analyzing. First, we observed that EA improved memory deficits and impaired synaptic plasticity. Moreover, EA possesses an ability to suppress the hyperphosphorylated tau and robust elevated NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in PS cDKO mice. Importantly, MCC950, a potent and selective inhibitor of NLPR3 inflammasome, has similar effects on inhibiting the hyperphosphorylated tau and the robust elevated NLRP3 components and neuroinflammatory responses of PS cDKO mice as well as EA treatment. Furthermore, EA treatment is not able to further improve the AD-like phenotypes of PS cDKO mice in combination with the MCC950 administration. Therefore, EA stimulation at GV 20 and GV 24 acupoints may be a potential alternative therapy for deterring cognitive deficits in AD through suppression of NLRP3 inflammasome activation.

Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI.Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed.Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation.Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

Electroacupuncture Alleviates Inflammation of Dry Eye Diseases by Regulating the α7nAChR/NF-κB Signaling Pathway.

Purpose We tried to investigate whether electroacupuncture (EA) can reduce inflammation of dry eye disease (DED) by regulating α7nAChR and inhibiting the NF-κB signaling pathway. Methods Healthy New Zealand white rabbits were treated with scopolamine hydrobromide (Scop) for 21 consecutive days to establish the DED animal model. After 21 days, EA, fluorometholone (Flu), and α7nAChR antagonist (α-BGT) treatments were performed, and the Scop injection was continued until day 35. During treatment, the fluorescence staining of the corneal epithelium and the level of tear flow were observed. The influence of EA on the LG pathology and inflammatory factors ACh, α7nAChR, and NF-κB was detected using the LG histopathology, transmission electron microscopy (TEM), cytokine protein chip technology, enzyme-linked immunosorbent assay (ELISA), and Western blot. Results The EA stimulation can reduce the corneal epithelial damage and repair epithelial cell ultrastructure, promote the tear secretion, relieve the LG atrophy and decrease lipid droplet accumulation in LG acinar cell, and reduce the levels of inflammatory cytokines (i.e., IL-1, MIP-1b, TNF-α, and IL-8) in the LG. The protective effect of EA on the inflammation and the ocular surface is similar to the corticosteroid Flu. EA and Flu can upregulate the expression of the α7nAChR and downregulate the expression of NF-κB. The α7nAChR antagonist α-BGT can reverse the protective effect of EA on the LG and the inhibitory effect on the NF-κB pathway and the expression of inflammatory factors but cannot affect the expression of Flu on the NF-κB pathway and inflammatory factors. Conclusion These results prove that EA can alleviate DEDs by stimulating the acupoints around the eyes. These beneficial effects are related to the upregulation of α7nAChR and the downregulation of NF-κB in the LG. The protective effect of LG is mediated through the anti-inflammatory pathway mediated by α7nAChR. EA can reduce the NF-κB P65 nuclear transcription and reduce inflammatory factors by regulating α7nAChR. This expression indicates that the α7nAChR/NF-κB signaling pathway may serve as a potential therapeutic target for EA to treat DEDs.

Electroacupuncture Attenuates CFA-Induced Inflammatory Pain by Regulating CaMKII.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase that is ubiquitously distributed in the central and peripheral nervous systems. Moreover, its phosphorylated protein (P-CaMKII) is involved in memory, mood, and pain regulation in the anterior cingulate cortex (ACC). Electroacupuncture (EA) is a traditional Chinese therapeutic technique that can effectively treat chronic inflammatory pain. However, the CaMKII-GluA1 role in EA analgesia in the ACC remains unclear. This study investigated the role of P-CaMKII and P-GluA1 in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). There were increased P-CaMKII and P-GluA1 levels in the ACC. We found that intracerebroventricular injection of KN93, a CaMKII inhibitor, as well as EA stimulation, attenuated complete Freund's adjuvant-induced pain behavior. Further, EA increased pCaMKII-PICK1 complex (abbreviated as C-P complex) levels. Our findings demonstrate that EA inhibits inflammatory pain by inhibiting CaMKII-GluA1 phosphorylation. P-CaMKII is involved in EA analgesia as the pCaMKII-PICK1 complex.

Regulated aberrant amygdala functional connectivity in premenstrual syndrome via electro-acupuncture stimulation at sanyinjiao acupoint（SP6）

Background: Acupuncture is an effective therapy for premenstrual syndrome (PMS). However, the mechanisms behind this method are still unclear. Our previous study found that aberrant amygdala resting-state functional networks were involved in PMS. Thereby, a deep investigation on the alterations of amygdala resting-state functional networks induced by acupuncture stimulation might contribute to a better understanding of the intricate mechanisms of acupuncture treatment on PMS. Methods: Twenty three PMS patients were recruited in this study. All patients received a 6-minute electro-acupuncture stimulation (EAS) at Sanyinjiao acupoint (SP6) and underwent two 6-minute resting-state fMRI scannings before and after EAS. With amygdala as the seed region, functional connectivity (FC) method was adopted to examine EAS-related modulation of intrinsic connectivity in PMS patients by comparing pre-EAS. Results: The results showed that EAS at SP6 induced increased FC between the left amygdala and brainstem, right hippocampus, and decreased FC between the left amygdala and left thalamus, bilateral supplementary motor area (SMA). Moreover, the results also showed that EAS at SP6 induced increased FC between the right amygdala and brainstem, right hippocampus, right orbitofrontal cortex, bilateral anterior cingulate cortex (ACC), and decreased FC between the right amygdala and right SMA. Conclusions: Based on the results of our previous study, our findings might improve our understanding of neural mechanisms behind acupuncture effects on PMS.

Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation.

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1-20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.

The Preventive Effect of Computed Tomography Image–Guided Electroacupuncture Combined with Continuous Femoral Nerve Block on Deep Vein Thrombosis After Total Knee Arthroplasty Based on an Adaptive Algorithm

Based on an adaptive algorithm model, this study proposed 2 special model structures of randomized fusion and an optimized convolution kernel and use it for image recognition. The adaptive algorithm model combined image-guided electroacupuncture with a continuous femoral nerve block to prevent deep vein thrombosis after total knee arthroplasty. A total of 200 patients after total knee arthroplasty were randomly divided into 4 groups. We assessed the incidence of postoperative lower limb deep vein thrombosis and platelet count before and after surgery. Electroacupuncture combined with continuous femoral nerve block can reduce the incidence of deep vein thrombosis and has obvious advantages in multimode prevention. The effective analgesia provided by electroacupuncture combined with continuous femoral nerve block relieved postoperative pain. It also enabled patients to participate in joint movement and lower limb muscle strength training as soon as possible, which not only is conducive to postoperative functional recovery, but also reduces the body stress response triggered by pain and the hypercoagulable state. Moreover, electroacupuncture stimulation of electroacupuncture points can reduce the inflammatory edema associated with surgery, improve blood circulation at the surgical site, and activate the body's anticoagulation mechanism. This study provides new ideas and references for formulating multimode prevention and control strategies.

Electroacupuncture and transcutaneous electrical acupoint stimulation with different intensities relieve muscular of inflammatory pain of the rats

To observe and compare the ameliorate effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) with different intensities on inflammatory muscle pain, so as to confirm the role of different afferent nerve fibers in different layers (skin or muscle) in pain relief of acupuncture. The intensities of the thresholds of A (Ta) and C (Tc) were selected for TEAS and EA. TEAS and EA were applied on the layer of skin and muscle of "Liangqiu" (ST34), respectively. Forty-eight rats were randomly divided into control, model, TEAS-Ta, TEAS-Tc, EA-Ta and EA-Tc groups (n=8 in each group). The inflammatory muscle pain model was established by complete Freund's adjuvant (CFA) injection into the right biceps femoris muscle. EA or TEAS was applied once a day for 3 days. The weight difference between the hind limbs and the abnormal electromyography (EMG) activities were observed as an index for pain of the rats. After modeling, the weight difference between the hind limbs was increased markedly in the model group relevant to the control group (P<0.01). Compared with the model group, the weight difference between the hind limbs in the TEAS-Tc, EA-Ta, and EA-Tc groups was significantly decreased (P<0.05, P<0.01). Compared with that before intervention, the area under the curve and discharge frequency of abnormal EMG of rats in the TEAS-Tc and EA-Ta groups were significantly reduced after intervention (P<0.01, P<0.05), while those in the EA-Tc group were significantly increased (P<0.05). After the intervention, compared with the TEAS-Ta group, the inhibition rate of the area under the curve and the discharge frequency of the abnormal EMG in the TEAS-Tc group increased significantly (P＜0.05); and those were also increased in the EA-Ta group when compared with the EA-Tc group (P<0.01). TEAS with Tc or EA with Ta in the muscle layer can alleviate the pain and inhibit the abnormal EMG in inflammatory muscle pain rats. It is indicated that local pain relief by acupuncture was related to the afferent nerve fiber in different layer with different intensities.

CaMKIIα-positive excitatory hippocampal neurons mediate "Zusanli" (ST36) electroacupuncture induced increase of gastric function in mice

To observe the effect of electroacupuncture (EA) stimulation of "Zusanli"(ST36)on gastric function (food consumption and gastric emptying rate) and excitability of hippocampal glutamatergic neurons in mice, so as to explore its mechanism underlying enhancing gastrointestinal function. The present study includes 2 parts. 1) C57BL/6 mice were randomly divided into normal and EA groups (n=12 in each group). EA (2 Hz/15 Hz, 1-3 mA) was applied to bilateral ST36 for 20 min, once daily for 7 days. In each group, 6 mice were used to measure the food consumption and gastric emptying rate, and the other 6 mice used to detect the hippocampal glutamate secretion content by using in vivo microdialysis and high performance liquid chromatography. 2) Thirty CaMKIIα-Cre mice received microinjection of a recombinant adeno-associated viral vector containing inhibitory designer receptor exclusively activated by a designer drug (DREADD, AAV-DIO-hM4Di-eYFP) into the hippocampus. Twenty-one days later, 3 mice were selected to observe the expression of eYFP-labeled hM4Di by immunohistochemistry, and 15 mice employed to observe the electrical activities of hM4Di-eYFP positive neurons exposed in chemogenetic activating drug Clozapine N-oxide (CNO) perfusion conditions (n=3) and without CNO in the recording chamber (n=6 in the control and EA groups) by using whole cell patch clamp. The rest 12 CaMKII-Cre mice were equally randomized into AAV-DIO-hM4Di-eYFP+CNO group and AAV-DIO-hM4Di-eYFP+CNO+EA group, and CNO was given by intraperitoneal injection for observing the effect of EA on gastric function. 1) In C57BL/6 mice, compared with the normal group, the food consumption, gastric emptying rate, and the glutamate content in the hippocampus were obviously increased in the EA group (P<0.01). 2) In CaMKIIα-Cre mice, the hM4Di-eYFP positive neurons distributing in the hippocampus showed an obvious increase of firing rates in the EA group relevant to the control group (P<0.01), and a hyperdepolarization potential after application of CNO. No significant changes were found between the AAV-DIO-hM4Di-eYFP+CNO and AAV-DIO-hM4Di-eYFP+CNO+EA groups in the food consumption and gastric emptying rate (P>0.05), suggesting an elimination of EA effect after acute DREADD-mediated activation of the CaMKIIα-positive hippocampal excitatory neurons. EA at ST36 can promote food intake and gastric emptying in normal mice but not in CaMKIIα-Cre mice with activated hippocampal hM4Di receptors，suggesting a contribution of the CaMKIIα-positive hippocampal excitatory neurons (glutamatergic neurons in particular) to the enhanced gastrointestinal function of EA at ST36.

Electroacupuncture improves obesity by lowering gastrointestinal motility, blood lipids and expression of intestinal leptin and cholecystokinin in obese rats

To investigate the effect of electroacupuncture (EA) on gastrointestinal motility and expression of leptin(LEP) and cholecystokinin(CCK) in the small intestine in obese rats，so as to explore the mechanism of EA underlying improvement of obesity. Male Wistar rats were randomized into 5 groups: normal control, obesity model, abdominal acupoints ［"Guanyuan" (CV4), "Zhongwan" (CV12) and bilateral "Tianshu" (ST25)］, lower-leg acupoints ［bilateral "Zusanli" (ST36) and bilateral "Fenglong" (ST40)］, and abdominal+ lower-leg acupoints (n=10 rats in each group). The obesity model was established by feeding the animals with high-fat diet for 8 weeks. EA was applied to the abovementioned acupoints for 20 min every time, 3 times a week for 8 weeks. The food intake and body mass were recorded. The white adipose tissue around the testicles and in the abdominal region was weighed. The serum total cholesterol (TC), triglyceride (TG) and non-esterified fatty acid(NEFA) were detected by using automatic biochemical analyzer. The gastric empty rate and intestinal propulsive rate were calculated. The contents of serum CCK and LEP were detected by using ELISA, and the expression levels of CCK and LEP proteins in the small intestine were detected by using Western blot. Following modeling, the food intake, body mass, weight of white adipose around the testicles and abdomen, the gastric empty rate, and serum TC, TG, NEFA and LEP contents as well as intestinal LEP expression were significantly increased (P<0.05, P<0.01), while the intestinal propulsive rate, serum CCK content and intestinal CCK expression were evidently decreased (P<0.01) in the model group relevant to the normal control group. After EA interventions and compared with the model group, the increased levels of food intake, body mass, white adipose weight, gastric empty rate, TC, TG, and LEP in serum and small intestine, and the decreased levels of intestinal propulsive rate, CCK in the serum and intestine were reversed in the abdominal acupoints, lower-leg acupoints and abdominal+lower-leg acupoints groups (P<0.05, P<0.01). No significant differences were found in the effects of the three EA groups in down-regulating food intake, body mass, white adipose weight, gastric empty rate, serum TC, TG and LEP levels (except NEFA) and in up-regulating intestinal propulsive rate and CCK level (P>0.05). EA stimulation of the abdominal and lower-leg acupoints or both can reduce body weight on obesity rats, which is associated with its functions in regulating intestinal motility, food intake, and secretion of LEP and CCK.