Low-frequency Electroacupuncture Research Articles

Spinal Nerve Root Electroacupuncture for Symptomatic Treatment of Lumbar Spinal Canal Stenosis Unresponsive to Standard Acupuncture: A Prospective Case Series

To study the effectiveness of electroacupuncture of the spinal nerve root using a selective spinal nerve block technique for the treatment of lumbar and lower limb symptoms in patients with lumbar spinal canal stenosis. Subjects were 17 patients with spinal canal stenosis who did not respond to 2 months of general conservative treatment and conventional acupuncture. Under x-ray fluoroscopy, two acupuncture needles were inserted as close as possible to the relevant nerve root, as determined by subjective symptoms and x-ray and MRI findings, and low-frequency electroacupuncture stimulation was performed (10 Hz, 10 min). Patients received 3-5 once-weekly treatments, and were evaluated immediately before and after each treatment and 3 months after completion of treatment. After the first nerve root electroacupuncture stimulation, scores for lumbar and lower limb symptoms improved significantly (low back pain, p<0.05; lower limb pain, p<0.05; lower limb dysaesthesia, p<0.01) with some improvement in continuous walking distance. Symptom scores and continuous walking distance showed further improvement before the final treatment (p<0.01), and a significant sustained improvement was observed 3 months after completion of treatment (p<0.01). Lumbar and lower limb symptoms, for which conventional acupuncture and general conservative treatment had been ineffective, improved significantly during a course of electroacupuncture to the spinal nerve root, showing sustained improvement even 3 months after completion of treatment. The mechanisms of these effects may involve activation of the pain inhibition system and improvement of nerve blood flow.

Role of neuropeptide Y in regulating hypothalamus–pituitary–gonad axis in the rats treated with electro-acupuncture

Neuropeptide Y (NPY) is an important regulator of reproductive axis, which mainly plays some roles in regulating secretion of gonadotropin-releasing hormone (GnRH) in hypothalamus. In previous studies, we found that the repeated low frequency electro-acupuncture (EA) down-regulated hypothalamus-pituitary-gonad (HPG) axis of common rats and rabbits during puberty. In this study, we investigated the role of NPY in regulating the reproductive axis of common rats at different developmental stages and rats treated with the repeated EA. Low frequency EA (3 Hz) was performed at acupoints (treatment groups) or non-acupoints (control groups) for 20 min daily for 10 days in Sprague-Dawley (SD) rats at four developmental stages, which were juvenile stage, early puberty stage, later puberty stage and adult stage. NPY expression in the hypothalamus were determined using RT-PCR and real-time quantitative PCR (qPCR) after 10 days-treatments. The results showed that NPY expression in the early pubertal group (EPG) was significantly depressed after repeated EA (P<0.05). Compared with the results of GnRH expression and body weights, the change of NPY expression was similar with the fluctuation of GnRH expression after EA and the increase of body weights of rats was not influenced by the depression of NPY expression after EA during early puberty. The results demonstrated that repeated low frequency EA was an effective method on down-regulating not only the GnRH expression but also the NPY expression in the hypothalamus without reducing body weights of rats during early puberty.

Antinociceptive and anti-inflammatory effects of electroacupuncture on experimental arthritis of the rat temporomandibular joint

This study investigated the antinociceptive and anti-inflammatory effects of electroacupuncture (EA) on zymosan-induced acute arthritis of the rat temporomandibular joint (TMJ). Male Wistar rats were injected with saline or zymosan (control group; 2mg) into the left TMJ. Low frequency EA (10Hz, 30min) was performed at acupoints (LI4, LI11, ST36, ST44) or sham points 2h after or 1h before zymosan administration. Mechanical hypernociception was accessed by the electronic Von Frey method after zymosan administration. Rats were sacrificed 6h after zymosan administration and the joint was removed for histopathological analysis, myeloperoxidase activity assessment, vascular permeability observations, and immunohistochemical verification of inflammatory mediators. The results showed that EA inhibited zymosan-induced hypernociception, compared with the control group and with the sham group (p< 0.05). The results showed that EA inhibited inflammatory parameters such as neutrophil migration, vascular permeability, and tumour necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in the TMJ compared with the sham group (p < 0.05). Histopathological analysis showed that EA significantly inhibited edema and periarticular infiltration (p< 0.05) compared with the control and sham groups. EA at acupoints produced antinociceptive and anti-inflammatory effects on zymosan-induced arthritis in the rat TMJ.

Electroacupuncture frequency‐related transcriptional response in rat arcuate nucleus revealed region‐distinctive changes in response to low‐ and high‐frequency electroacupuncture

Electroacupuncture (EA) has been clinically applied for treating different medical conditions, such as pain, strain, and immune diseases. Low- and high-frequency EAs have distinct therapeutic effects in clinical practice and experimental studies. However, the molecular mechanism of this difference remains obscure. The arcuate nucleus (Arc) is a critical region of the hypothalamus and is responsible for the effect of EA stimulation to remote acupoints. Gene expression profiling provides a powerful tool with which to explore the basis of physiopathological responses to external stimulus. In this study, using cDNA microarray, we investigated gene expressions in the rat Arc region induced by low-frequency (2-Hz) and high-frequency (100-Hz) EAs to two remote acupoints, zusanli (ST36) and sanyinjiao (SP6). We have found that more genes were differentially regulated by 2-Hz EA than 100-Hz EA (154 vs. 66 regulated genes/ESTs) in Arc, especially those related to neurogenesis, which was confirmed by qRT-PCR. These results demonstrate that the expression level of genes in the Arc region could be effectively regulated by low-frequency EA, compared with high-frequency EA, helping to uncover the mechanisms of the therapeutic effects of the low-frequency EA. Our results also indicate different-frequency EAs are spatially specific.

Electrical and manual acupuncture stimulation affect oestrous cyclicity and neuroendocrine function in an 5α‐dihydrotestosterone‐induced rat polycystic ovary syndrome model

Both low-frequency electro-acupuncture (EA) and manual acupuncture improve menstrual frequency and decrease circulating androgens in women with polycystic ovary syndrome (PCOS). We sought to determine whether low-frequency EA is more effective than manual stimulation in regulating disturbed oestrous cyclicity in rats with PCOS induced by 5α-dihydrotestosterone. To identify the central mechanisms of the effects of stimulation, we assessed hypothalamic mRNA expression of molecules that regulate reproductive and neuroendocrine function. From age 70 days, rats received 2 Hz EA or manual stimulation with the needles five times per week for 4-5 weeks; untreated rats served as control animals. Specific hypothalamic nuclei were obtained by laser microdissection, and mRNA expression was measured with TaqMan low-density arrays. Untreated rats were acyclic. During the last 2 weeks of treatment, seven of eight (88%) rats in the EA group had epithelial keratinocytes, demonstrating oestrous cycle change (P = 0.034 versus control rats). In the manual group, five of eight (62%) rats had oestrous cycle changes (n.s. versus control animals). The mRNA expression of the opioid receptors Oprk1 and Oprm1 in the hypothalamic arcuate nucleus was lower in the EA group than in untreated control rats. The mRNA expression of the steroid hormone receptors Esr2, Pgr and Kiss1r was lower in the manual group than in the control animals. In rats with 5α-dihydrotestosterone-induced PCOS, low-frequency EA restored disturbed oestrous cyclicity but did not differ from the manual stimulation group, although electrical stimulation lowered serum testosterone in responders, those with restored oestrus cyclicity, and differed from both control animals and the manual stimulation group. Thus, EA cannot in all aspects be considered superior to manual stimulation. The effects of low-frequency EA may be mediated by central opioid receptors, while manual stimulation may involve regulation of steroid hormone/peptide receptors.

P-150 - Effects of low-frequency electroacupuncture on the BIS and anxiety in anxious volunteers: a prospective, randomized, blinded study

Acupuncture is a low-risk intervention that is increasingly used. Some studies examined the potential effects of acupuncture on anxiety and the bispectral index of the EEG (BIS), used as an objective and indirect measure of anxiolysis. Those studies used the same acupuncture point and achieved conflicting results. To objectively assess the effects of acupuncture on anxiety and the BIS on a clinically relevant population. To evaluate the impact of alternative, low risk interventions, such as acupuncture in anxiety. 15 anxious volunteers were recruited for this prospective, controlled, blinded, crossover study with random allocation. Acupuncture was performed at the experimental point He7 (Heart 7) and at a control point Lu 9 (Lung 9). BIS was evaluated at 3 different stages, rest state, during electro-acupuncture and post acupuncture. BIS mean values and minimums means were significantly reduced by acupuncture on He7 compared to acupuncture on Lu9 (means: 90,7 ± 4,3 to 86,5 ± 7,2; p = 0,009 | minimums: 80,6 ± 9,6 to 71,9 ± 12,3; p = 0,011). None of the groups had a significant decrease in BIS comparing acupuncture to the rest state, however acupuncture on He7 was related to a relevant (but statistically nonsignificant) decrease in BIS mean compared to the rest state. Acupuncture on He7 was superior over acupuncture on Lu9 to decrease BIS in anxious volunteers and showed objective and measurable cerebral effects.

Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid.

Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.

Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial

To investigate the possible effects of low-frequency electroacupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with polycystic ovary syndrome (PCOS). Secondary analyses of a prospective, randomized controlled clinical trial. Department of Physiology and Department of Obstetrics and Gynecology, University of Gothenburg. Eighty-four women with PCOS were randomized. Women with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/wk), or no intervention. Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16-week follow-up. In the low-frequency EA group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed from the physical exercise and the no intervention groups. The EA group had decreases in circulating fibrinogen and tissue plasminogen activator (t-PA), sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in plasminogen activator inhibitor 1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied.

Retrosplenial Cortex is Involved in Analgesia Induced by 2- but not 100-Hz Electroacupuncture in the Rat Tail-Flick Test

This study examined whether or not the antinociceptive effect of 2- or 100-Hz electroacupuncture (EA) depends on the integrity of the retrosplenial cortex (RSC). Rats were taken for determination of tail-flick latency before and after injection of saline or 2% lidocaine (0.25μl) into the retrosplenial cortex (RSC) bilaterally. Five minutes later, they were submitted to a 20-minute period of 2Hz, 100Hz, or sham EA at the Zusanli and Sanyinjiao acupoints bilaterally, and tail-flick latency was measured within 30 seconds after the end of stimulation and at 5-minute intervals for up to 30 minutes. EA at a frequency of either 2 or 100Hz induced a strong and long-lasting inhibition of the tail-flick reflex in rats treated with saline (0.25μl) injected into the RSC. The analgesia produced by 2-Hz EA lasted for a shorter time in lidocaine-treated rats. By contrast, RSC impairment did not change the analgesic effect of 100Hz EA. The integrity of the RSC is implicated in the duration of analgesia induced by low-frequency EA but is not essential for the analgesic effects evoked by high-frequency EA.

Low frequency electroacupuncture selectively decreases voluntarily ethanol intake in rats

Although there is increasing clinical acceptance of acupuncture and electroacupuncture (EA) as a treatment of substance abuse-related disorders, our understanding of this treatment remains incomplete. Previous clinical and pre-clinical studies have shown that acupuncture and EA are effective in reducing ethanol consumption. Recent studies have shown that Sprague-Dawley (SD) rats under an intermittent-access two-bottle choice drinking procedure (IE procedure) voluntarily drank high amounts of ethanol. However, an effect of EA on ethanol consumption of the SD rats under this drinking procedure has not been demonstrated.In the present study, we demonstrated that SD rats escalated their ethanol intake and subsequently developed ethanol dependence under the IE procedure. A single low (2Hz), but not high frequency (100Hz) EA treatment applied at the bilateral acupoint Zusanli (ST36), but not at the tail reduced voluntary intake of, and preference for ethanol, but not sucrose. Furthermore, repeated EA treatments decreased the intake of and preference for ethanol, without resulting in a rebound increase in ethanol intake when the EA treatments were terminated. These observations indicate that EA may be a useful treatment for alcohol abuse.

Comparison of Electroacupuncture Frequency-related Effects on Heart Rate Variability in Healthy Volunteers: A Randomized Clinical Trial

AbstractThis study aimed to compare the effects of high frequency electroacupuncture (EA) and low-frequency EA on the autonomic nervous system by using a heart rate variability measuring device in normal individuals. Fourteen participants were recruited and each participated in the high-frequency and low-frequency sessions (crossover design). The order of sessions was randomized and the interval between the two sessions was over 2 weeks. Participants received needle insertion with 120-Hz stimulation during the high-frequency session (high-frequency EA group), and with 2-Hz stimulation during the low-frequency session (low-frequency EA group). Acupuncture needles were directly inserted perpendicularly to LI 4 and LI 11 acupoints followed by delivery of electric pulses to these points for 15 minutes. Heart rate variability was measured 5 minutes before and after EA stimulation by a heart rate variability measuring system. We found a significant increase in the standard deviation of the normal-to-normal interval in the high-frequency EA group, with no change in the low-frequency EA group. Both the high-frequency and low-frequency EA groups showed no significant differences in other parameters including high-frequency power, low-frequency power, and the ratio of low-frequency power to high-frequency power. Based on these findings, we concluded that high-frequency EA stimulation is more effective than low-frequency EA stimulation in increasing autonomic nervous activity and there is no difference between the two EA frequencies in enhancing sympathovagal balance.

Electroacupuncture With High Frequency at Acupoint ST-36 Induces Regeneration of Lost Enteric Neurons in Diabetic Rats via GDNF and PI3K/AKT Signal Pathway

Background electroacupuncture (EA) at acupoint ST-36 (Zusanli) has been used to alleviate gastrointestinal symptoms and improve gastrointestinal motility, but the effects and mechanisms of EA on enteric nervous system (ENS) have scarcely been investigated. SD rats were randomly divided into eight groups: normal control group, diabetes mellitus group (DM), chronic high-frequency EA (C-HEA), chronic low-frequency EA (C-LEA), chronic sham stimulation group (C-SEA), acute high-frequency EA group (A-HEA), acute low-frequency EA group (A-LEA), and diabetic with acute sham stimulation group (A-SEA). The parameters of HEA included a frequency of 100 Hz and an amplitude of 1 mA, while the parameters for LEA were 10 Hz and 1 mA. The expressions of PGP9.5, neuronal nitric oxide synthase neurons, CHAT neurons, glia cell line-derived neurotrophic factor (GDNF) and p-Akt were measured by immunofluorescence or immunohistochemistry, real-time PCR, and Western blotting methods in colon tissues of each rat. The total neuro...

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats

Diabetes is considered the leading cause of neuropathies in developed countries. Dysfunction of nerve growth factor (NGF) production and/or utilisation may lead to the establishment of diabetic neuropathies. Electroacupuncture has been proved effective in the treatment of human neuropathic pain as well as in modulating NGF production/activity. We aimed at using electroacupuncture to correct the development of thermal hyperalgesia and the tissue alteration of NGF and sensory neuromodulators in a rat model of type 1 diabetes. Adult rats were injected with streptozotocin to induce diabetes and subsequently treated with low-frequency electroacupuncture for 3 weeks. Variation in thermal sensitivity was studied during the experimental course. Hindpaw skin and spinal cord protein content of NGF, NGF receptor tyrosine kinase A (TrkA), substance P (SP), transient receptor potential vanilloid 1 (TRPV1) receptor and glutamic acid decarboxylase-67 (GAD-67) were measured after electroacupuncture treatments. The skin and spinal cord cellular distribution of TrkA was analysed to explore NGF signalling. Early after streptozotocin treatment, thermal hyperalgesia developed that was corrected by electroacupuncture. The parallel increases in NGF and TrkA in the spinal cord were counteracted by electroacupuncture. Streptozotocin also induced variation in skin/spinal TrkA phosphorylation, increases in skin SP and spinal TRPV1 and a decrease in spinal GAD-67. These changes were counteracted by electroacupuncture. Our results point to the potential of electroacupuncture as a supportive therapy for the treatment of diabetic neuropathies. The efficacy of electroacupuncture might depend on its actions on spinal/peripheral NGF synthesis/utilisation and normalisation of the levels of several sensory neuromodulators.

A Parametric Study on the Immunomodulatory Effects of Electroacupuncture in DNP-KLH Immunized Mice.

This study was conducted to compare the effects of low frequency electroacupuncture (EA) and high frequency EA at acupoint ST36 on the production of IgE and Th1/Th2 cytokines in BALB/c mice that had been immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH), as well as to investigate the difference in the immunomodulatory effects exerted by EA stimulations at acupoint ST36 and at a non-acupoint (tail). Female BALB/c mice were divided into seven groups: normal (no treatments), IM (immunization only), ST36-PA (IM + plain acupuncture at ST36), ST36-LEA (IM + low frequency (1 Hz) EA at ST36), ST36-HEA (IM + high frequency (120 Hz) EA at ST36), NA-LEA (IM + low frequency (1 Hz) EA at non-acupoint) and NA-HEA (IM + high frequency (120 Hz) EA at non-acupoint). EA stimulation was performed daily for two weeks, and total IgE, DNP-KLH specific IgE, IL-4 and IFN-γ levels were measured at the end of the experiment. The results of this study showed that the IgE and IL-4 levels were significantly suppressed in the ST36-LEA and ST36-HEA groups, but not in the NA-LEA and NA-HEA groups. However, there was little difference in the immunomodulatory effects observed in the ST36-LEA and ST36-HEA groups. Taken together, these results suggest that EA stimulation-induced immunomodulation is not frequency dependent, but that it is acupoint specific.

Electroacupuncture analgesia, stress responses, and variations in sensitivity in rats anesthetized with different sub-MAC anesthetics

The use of anesthetics to stabilize animals for the purpose of electroacupuncture (EA) analgesic studies can be problematic because of the interference of differential physiological responses to EA and pain. In this study, EA-induced physiological profiles were surveyed under a sub-minimal alveolar concentration (sub-MAC) of two different anesthetics in a previously proposed minimal stress model. First, to select an adequate concentration, compliance with EA and tail-flick stimulation was evaluated under various concentrations of halothane and isoflurane. Second, using the chosen concentrations, low- (4-Hz) and high-frequency (100-Hz) EA were conducted on the right hind limb. The EA effects of the two gases were compared by tail-flick latency (TFL), hemodynamic variables, and individual variations in analgesic sensitivity. The optimal concentrations for halothane and isoflurane were 0.5% and 0.75%, respectively. TFLs were stable under these anesthetic levels, but rats under 0.75% isoflurane had better compliance than those under 0.5% halothane. EA inhibited TFLs with distinct analgesic patterns when comparing high- and low-frequency EA, but TFL suppression did not differ between the two gases. Heart rate and blood pressure showed temporal and differential responses to low- vs. high-frequency EA, but were comparable between groups under the two anesthetics. The ratios of EA non-responders in the isoflurane and halothane groups were 32.4% and 26.7%, respectively, without statistical difference. We concluded that sub-MAC halothane and isoflurane provide optimal conditions for the study of EA-induced analgesia in rats. In this model, 0.75% isoflurane appears to be a better choice than 0.5% halothane in terms of EA compliance.

Experimental study of low-frequency electroacupuncture-induced differentiation of bone marrow mesenchymal stem cells into chondrocytes

In the present study, we investigated the effect of low-frequency electroacupuncture (EA) on the differentiation of bone mesenchymal stem cells (BMSCs) into chondrocytes and the molecular mechanism involved. We isolated BMSCs from Sprague-Dawley (SD) rat bone marrow. Third-generation SD rat BMSCs (P3 BMSCs) were harvested and characterized by flow cytometry with FITC staining. Data indicated that the positive rates of CD90 and CD45 were 98.22 and 1.91%, respectively, indicating the high purity of the BMSCs. The P3 BMSCs were treated with EA for 15 or 30 min daily for 7 or 14 days. Using optical microscopy and transmission electron microscopy, we found that EA induced morphological changes in the BMSCs, displaying typical morphology of early chondrocytes. In addition, we found that the cytoplasm and extracellular matrices were metachromatically stained by toluidine blue in the treated cells in a dose-dependent manner, indicating that EA treatment resulted in the expression of glycosaminoglycan. Furthermore, upon immunohistocytochemical staining and Western blotting, we found that EA treatment significantly and dose-dependently induced expression of chondrocyte-specific matrix protein type II collagen, which may have been mediated by the transcription factor Sox9, as the mRNA expression of Sox9 was found to be significantly increased after EA treatment. Taken together, these results suggest that EA can be employed as a novel non-drug-inducing method for the differentiation of BMSCs into chondrocytes.

Low‐Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice through Activation of SIRT1/PGC‐1α in Skeletal Muscle

Electroacupuncture (EA) has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1) and induced gene expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and acyl-CoA oxidase (ACOX). These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-1α, thus resulting in improved insulin signal.

Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Activation of reciprocal pathways between arcuate nucleus and ventrolateral periaqueductal gray during electroacupuncture: Involvement of VGLUT3

Electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, overlying the median nerve) attenuates sympathoexcitatory responses through activation of the arcuate nucleus (ARC) and ventrolateral periaqueductal gray (vlPAG). Activation of the ARC or vlPAG respectively leads to neuronal excitation of the both nuclei during EA. However, direct projections between these two nuclei that could participate in central neural processing during EA have not been identified. The vesicular glutamate transporter 3 (VGLUT3) marks glutamatergic neurons. Thus, the present study evaluated direct neuronal projections between the ARC and vlPAG during EA, focusing on neurons containing VGLUT3. Seven to ten days after unilateral microinjection of a rodamine-conjugated microsphere retrograde tracer (100 nl) into the vlPAG or ARC, rats were subjected to EA or served as a sham-operated control. Low frequency (2 Hz) EA was performed bilaterally for 30 min at the P5–P6 acupoints. Perikarya containing the microsphere tracer were found in the ARC and vlPAG of both groups. Compared to controls (needle placement without electrical stimulation), c-Fos immunoreactivity and neurons double-labeled with c-Fos, an immediate early gene and the tracer were increased significantly in the ARC and vlPAG of EA-treated rats (both P < 0.01). Moreover, some neurons were triple-labeled with c-Fos, the retrograde tracer and VGLUT3 in the two nuclei following EA stimulation ( P < 0.01, both nuclei). These results suggest that direct reciprocal projections between the ARC and vlPAG are available to participate in prolonged modulation by EA of sympathetic activity and that VGLUT3-containing neurons are an important neuronal phenotype involved in this process.

Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20-25 min five times/wk for 4-5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.