Hz Electroacupuncture Research Articles

High frequency electro-acupuncture enhances striatum DAT and D1 receptor expression, but decreases D2 receptor level in 6-OHDA lesioned rats

The direct effects of electro-acupuncture (EA) on the dopaminergic neurotransmitter system in Parkinson's disease (PD) patients remain elusive. In the present study, 0, 2 or 100Hz EA was applied to acupoints Sanyinjiao (SP6), Yanglingquan (GB34) and Zusanli (ST36) in a rat model unilaterally lesioned by 6-hydroxydopamine. Rotational behavior tests were performed and the animals were then decapitated. Levels of striatal dopamine (DA), dopamine transporter, and D1- and D2-like DA receptors were subsequently evaluated. EA at 100Hz was shown to significantly enhance survival of dopaminergic neurons in the substantia nigra (52.10±11.41% of the level on the non-lesioned rats vs. 21.22±5.52% in the non-EA group, P<0.05) and reduce motor deficits (207.80±31.14 vs. 476.11±68.80turns/30min, P<0.05), whereas it only slightly restored the 6-hydroxydopamine-induced loss of striatal DA (P>0.05 vs. the non-EA group). There was a 253.78% increase in dopamine transporter protein expression in the striatum in the 100Hz EA group (P<0.05 vs. the non-EA group). Moreover, high frequency EA induced increases in striatal D1-like receptor mRNA and protein levels of 81.88% and 62.62%, respectively (P<0.001 and P<0.05 vs. the non-EA group). However, the D2-like DA receptor up-regulation observed in the non-EA group was suppressed in high frequency group (P>0.05 vs. the sham operation group). These findings suggest that high-frequency EA might work by acting on presynaptic dopamine transporter and postsynaptic dopamine receptors simultaneously to achieve a therapeutic effect in PD patients and models. This might shed some light on the mechanism by which EA affects the DA neurotransmitter system.

Protecting action of acupuncture-drug compound anesthesia with different frequency electroacupuncture on stress reaction in patients of pneumonectomy

ObjectiveTo observe the protective effect of acupuncture-drug compound anesthesia with different frequency electroacupuncture (EA) on stress reaction in patients of pneumonectomy and to explore potential mechanisms. MethodsEighty patients scheduled for pneumonectomy were randomly divided into four groups, group A, B, C and D, 20 cases in each group. General anesthesia and single lung protective mechanical ventilation were carried out in all the groups. Acupuncture was given at Hòuxī (▪ SI 3), Zhīgōu (▪ TE 6), Nèiguān (▪ PC 6), and Hégŭ (▪ LI 4) 30 min before general anesthesia, and the acupuncture needles were connected with Han's acupoint nerve stimulator (HANS-200) in all the groups, but the acupuncture needles without needle bodies were pasted on the acupoints and EA was not given in the group A. 2 Hz continuous wave, 100 Hz continuous wave and 2 Hz/100 Hz EA were given in the group B, C and D respectively. The supplementary amount of anesthesia medicine, heart rate (HR) and mean arterial pressure (MAP) during pneumonectomy, and CD+4/CDCD+8 in venous blood before and one day after the surgery, and the contents of epinephrine (E) and Cortisol (Cor) in plasma after entering the operating room and before turning out the operating room were detected. Results▪ During the operation, supplementary amounts of Fentanyl in the group B and C were lower than those in the group A and D (P<0.05, P<0.01). ▪ The MAP in the four groups at tracheal intubation (T1) all were higher than those before anesthesia (T0) (all P<0.01), and the ascending extents in the group B, C and D were lower than that in the group A (all P<0.01); HR at T1 in the group A was higher than that at T0 (P<0.05), while no significant change in the other groups (all P>0.05), and the ascending extents in the group B and D were lower than that in the group A (both P<0.05); MAP and HR at the other moments in all the groups were stable. ▪ CD+4/CD+8 in the group A after pneumonectomy was lower than that before the surgery (P<0.05), while no significant change in the other groups (all P>0.05). ▪ Contents of E and Cor after the operation were significantly increased in all the groups (all P<0.01), and the ascending extent of E content in the group D was lower than that in the group A (P<0.05); the ascending level of Cor in the group B and D was lower than that in the group A (P<0.01), and in the group B was lower that in the group C and D. ConclusionAcupuncture-drug compound anesthesia can attenuate the stress reaction so as to protect organs under the condition of less or same narcotic amount and can alleviate the fluctuation of MAP and HR at tracheal intubation and stabilize CD+4/CD+8 after pneumonectomy. Among them, 2 Hz and 2 Hz/100 Hz EA have better effects.

Abstract 413: Electroacupuncture Improves Arterial Baroreflex and Chemoreflex Sensitivity in Angiotensin II-induced Hypertension in Rats

Despite the use of electroacupuncture (EA) to treat a number of cardiovascular diseases, little is known about the mechanisms that underlie its actions. It is well known that renin-angiotensin system plays a major role in pathogenesis of hypertension. The purpose of this study was to examine the influence of EA stimulation of ST 36 on arterial baro- and chemoreflex sensitivity in angiotensin (Ang) II-induced hypertension in rats. Four groups of SD rats (n=8/group) were implanted with subcutaneous osmotic minipumps for infusion of Ang II (300 ng/kg/min) or saline control, with or without EA stimulation. EA groups underwent a 2 Hz EA treatment at the acupoints ST36 or a non-acupoint with the intensity increasing stepwise from 0.5-1-1.5 mA once a day for 30 min. Baroreflex sensitivity index was calculated on the basis of reflex changes in heart rate (HR) related to the arterial pressure (AP) changes induced by phenylephrine or sodium nitroprusside injection, and chemoreflex sensitivity was evaluated by intravenous injections of increasing doses of potassium cyanide (KCN). After 4 weeks of treatment, Ang II significantly increased mean arterial pressure (107±2 and 139±2 mmHg in control vs. Ang II group). Baroreflex sensitivity to AP rises and falls were also impaired in Ang II infusion group (1.3±0.08 and 2.1 ±0.18 bpm/mmHg) compared with those in control group (1.7±0.08 and 2.7±0.06 bpm/mmHg). EA stimulation of ST 36 on Ang II infusion rats significantly improved the impaired baroreflex sensitivity (1.7±0.06 and 2.6±0.1 bpm/mmHg, P &lt; 0.05). In addition, the bradycardic and pressor responses evoked by KCN injections were attenuated in Ang II infusion rats (23±9 bpm and 7±1 mmHg in Ang II group vs. 78±7 bpm and 22±3mmHg in control group, P &lt; 0.05), while EA stimulation improved both chemoreflex responses in AngII rats (84±15 bpm and 32±5 mmHg, P&lt;0.05). In contrast, EA stimulation had no significant effect on control group. These results indicate that EA stimulation improves arterial baroreflex function and chemoreflex sensitivity in conditions of high Ang II.

High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

Differences in Neural-Immune Gene Expression Response in Rat Spinal Dorsal Horn Correlates with Variations in Electroacupuncture Analgesia

BackgroundElectroacupuncture (EA) has been widely used to alleviate diverse pains. Accumulated clinical experiences and experimental observations indicated that significant differences exist in sensitivity to EA analgesia for individuals of patients and model animals. However, the molecular mechanism accounting for this difference remains obscure.Methodology/Principal FindingsWe classified model male rats into high-responder (HR; TFL changes >150) and non-responder (NR; TFL changes ≤0) groups based on changes of their pain threshold detected by tail-flick latency (TFL) before and after 2 Hz or 100 Hz EA treatment. Gene expression analysis of spinal dorsal horn (DH) revealed divergent expression in HR and NR after 2 Hz/100 Hz EA. The expression of the neurotransmitter system related genes was significantly highly regulated in the HR animals while the proinflammation cytokines related genes were up-regulated more significantly in NR than that in HR after 2 Hz and 100 Hz EA stimulation, especially in the case of 2 Hz stimulation.Conclusions/SignificanceOur results suggested that differential regulation and coordination of neural-immune related genes might play an important role for individual variations in analgesic effects responding to EA in DH. It also provided new candidate genes related to EA responsiveness for future investigation.

Electroacupuncture decreases excessive alcohol consumption involving reduction of FosB/ΔFosB levels in reward-related brain regions.

New therapies are needed for alcohol abuse, a major public health problem in the U.S. and worldwide. There are only three FDA-approved drugs for treatment of alcohol abuse (naltrexone, acamprosate and disulfuram). On average these drugs yield only moderate success in reducing long-term alcohol consumption. Electroacupuncture has been shown to alleviate various drugs of abuse, including alcohol. Although previous studies have shown that electroacupuncture reduced alcohol consumption, the underlying mechanisms have not been fully elucidated. ΔFosB and FosB are members of the Fos family of transcription factors implicated in neural plasticity in drug addiction; a connection between electroacupuncture's treatment of alcohol abuse and the Fos family has not been established. In this study, we trained rats to drink large quantities of ethanol in a modified intermittent access two-bottle choice drinking procedure. When rats achieved a stable baseline of ethanol consumption, electroacupuncture (100 Hz or 2 Hz, 30 min each day) was administered at Zusanli (ST36) for 6 consecutive days. The level of FosB/ΔFosB in reward-related brain regions was assessed by immunohistochemistry. We found that the intake of and preference for ethanol in rats under 100 Hz, but not 2 Hz electroacupuncture regiment were sharply reduced. The reduction was maintained for at least 72 hours after the termination of electroacupuncture treatment. Conversely, 100 Hz electroacupuncture did not alter the intake of and preference for the natural rewarding agent sucrose. Additionally, FosB/ΔFosB levels in the prefrontal cortex, striatal region and the posterior region of ventral tegmental area were increased following excessive ethanol consumption, but were reduced after six-day 100 Hz electroacupuncture. Thus, this study demonstrates that six-day 100 Hz electroacupuncture treatment effectively reduces ethanol consumption and preference in rats that chronically drink excessive amount of ethanol. This effect of electroacupuncture may be mediated by down-regulation of FosB/ΔFosB in reward-related brain regions.

Electroacupunture reduces mechanical hyperalgesia produced by repeated intramuscular injections of acidic saline in rats

This study aimed to identify the effects of electroacupuncture in the mechanical hyperalgesia produced by repeated intramuscular injections of acidic saline. Twenty four male Wistar rats were divided in four groups (n = 6, in each group): control, acupuncture, electroacupuncture (EA) 15 Hz and electroacupuncture (EA) 100 Hz. Left gastrocnemius muscle from all animals was injected with 100 μL of sterile saline pH 4.0 twice five days apart. Electroacupuncture, acupuncture or control was daily administered (20 min) for 5 consecutive days under isoflurane anesthesia (1%–2%). Needles were placed in the Zuzanli (St36) and Sanyinjiao (SP6). Paw withdrawal threshold to mechanical stimuli was assessed before the two injections, and before and after the each stimulation by using von Frey filaments. The reduced paw withdrawal threshold that occurs 24 hours after the second injection was significantly reversed by the first administration of EA at both 100 Hz and 15 Hz when compared with sham treatment and baseline measures. The analgesic effect lasted for 4 and 3 days when 15 Hz and 100 Hz were applied, respectively. These data suggest that both 15 Hz and 100 Hz electroacupuncture are effective on reducing secondary mechanical hyperalgesia showing a long‐lasting effect. Research support: CAPES, Fapitec.

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.

2 Hz Electro-Acupuncture at Yinlingquan (SP9) and Ququan (LR8) Acupoints Induces Changes in Blood Flow in the Liver and Spleen

According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively.

Kappa-opioid receptors in the caudal nucleus tractus solitarius mediate 100 hz electroacupuncture-induced sleep activities in rats.

Previous results demonstrated that 10 Hz electroacupuncture (EA) of Anmian acupoints in rats during the dark period enhances slow wave sleep (SWS), which involves the induction of cholinergic activity in the caudal nucleus tractus solitarius (NTS) and subsequent activation of opioidergic neurons and μ-receptors. Studies have shown that different kinds of endogenous opiate peptides and receptors may mediate the consequences of EA with different frequencies. Herein, we further elucidated that high-frequency (100 Hz)-EA of Anmian enhanced SWS during the dark period but exhibited no direct effect on rapid eye movement (REM) sleep. High-frequency EA-induced SWS enhancement was dose-dependently blocked by microinjection of naloxone or κ-receptor antagonist (nor-binaltorphimine) into the caudal NTS, but was affected neither by μ- (naloxonazine) nor δ-receptor antagonists (natatrindole), suggesting the role of NTS κ-receptors in the high-frequency EA-induced SWS enhancement. Current and previous results depict the opioid mechanisms of EA-induced sleep.

The Cortical and Striatal Gene Expression Profile of 100 Hz Electroacupuncture Treatment in 6-Hydroxydopamine-Induced Parkinson's Disease Model

Electroacupuncture (EA), especially high-frequency EA, has frequently been used as an alternative therapy for Parkinson disease (PD) and is reportedly effective for alleviating motor symptoms in patients and PD models. However, the molecular mechanism underlying its effectiveness is not completely understood. To implement a full-scale search for the targets of 100 Hz EA, we selected rat models treated with 6-hydroxydopamine into the unilateral MFB, which mimic end-stage PD. High-throughput microarray analysis was then used to uncover the regulated targets in the cortex and striatum after 4-week EA treatment. In the differentially regulated transcripts, the proportion of recovered expression profiles in the genes, the functional categories of targets in different profiles, and the affected pathways were analyzed. Our results suggested that the recovery of homeostasis in the transcript network and many regulated functional clusters in the cortex and striatum after EA treatment may contribute to the behavioral improvement of PD rats.

Effects of Electroacupuncture onN-Methyl-D-aspartate Receptor-Related Signaling Pathway in the Spinal Cord of Normal Rats

This study examined the influence of the N-methyl-D-aspartate receptor (NMDAR) on the modulation of related spinal signaling after electroacupuncture (EA) treatment in normal rats. Bilateral 2 Hz EA stimulations (1-2-3.0 mA) were delivered at acupoints corresponding to Zusanli (ST36) and Sanyinjiao (SP6) in men for 30 min. Thermal sensitization was strongly inhibited by EA, but this analgesia was reduced by preintrathecal injection of the NMDAR antagonist, MK801. Phosphorylation of the NMDAR NR2B subunit, cAMP response element-binding protein (CREB), and especially phosphatidylinositol 3-kinase (PI3K) were significantly induced by EA. However, these marked phosphorylations were not observed in MK801-pretreated rats. EA analgesia was reduced by preintrathecal injection with the calcium chelators Quin2 and TMB8, similar to the results evident using MK801. Phosphorylation of PI3K and CREB induced by EA was also inhibited by TMB8. Calcium influx by NMDAR activation may play an important role in EA analgesia of normal rats through the modulation of the phosphorylation of spinal PI3K and CREB.

Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.

Amitriptyline prolongs the antihyperalgesic effect of 2‐ or 100‐Hz electro‐acupuncture in a rat model of post‐incision pain

The mechanisms through which electro-acupuncture (EA) and tricyclic antidepressants produce analgesia seem to be complementary: EA inhibits the transmission of noxious messages by activating supraspinal serotonergic and noradrenergic neurons that project to the spinal cord, whereas tricyclic antidepressants affect pain transmission by inhibiting the reuptake of norepinephrine and serotonin at the spinal level. This study utilized the tail-flick test and a model of post-incision pain to compare the antihyperalgesic effects of EA at frequencies of 2 or 100 Hz in rats treated with intraperitoneal or intrathecal amitriptyline (a tricyclic antidepressant). A gradual increase in the tail-flick latency (TFL) occurred during a 20-min period of EA. A strong and long-lasting reduction in post-incision hyperalgesia was observed after stimulation; the effect after 2 Hz lasting longer than after 100-Hz EA. Intraperitoneal or intrathecal amitriptyline potentiated the increase in TFL in the early moments of 2- or 100-Hz EA, and the intensity of the antihyperalgesic effect of 100-Hz EA in both the incised and non-incised paw. In contrast, it did not significantly change the intensity of the antihyperalgesic effect of 2-Hz EA. The EA-induced antihyperalgesic effects lasted longer after intraperitoneal or intrathecal amitriptyline than after saline, with this effect of amitriptyline being more evident after 100- than after 2-Hz EA. The synergetic effect of amitriptyline and EA against post-incision pain shown here may therefore represent an alternative for prolonging the efficacy of EA in the management of post-surgical clinical pain.

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.

The 2 Hz and 15 Hz electroacupuncture induced reverse effect on autonomic function in healthy adult using a heart rate variability analysis

The purpose of the present study was to investigate effect of electro-acupuncture (EA) at different frequencies on autonomic function. Twenty healthy adult volunteers were studied, and underwent 4 sessions of EA (sham, 2Hz, 15Hz, and 50Hz). Sham, 2Hz, 15Hz, and 50Hz EA was applied to the bilateral Leg Three Li (足三里 zú sān lǐ, ST-36) and Upper Great Hollow (上巨虛 shàng jù xū, ST-37) acupoints. The intensity of electrical stimulation was adjusted to obtain visible twitching of the anterior tibial muscle about 2.0-2.5mA except sham without electrical stimulation. The components of heart rate variability (HRV) and blood pressure were measured before EA (BLP), EA (EAP), and post-EA periods (PEP). The results indicated that the natural logarithmic high frequency power (lnHF) of HRV was greater during PEP than during the BLP in the 2Hz EA sessions. The natural logarithmic low frequency power (lnLF) of HRV was greater during the PEP than during the BLP in 15Hz EA sessions, suggesting that 2Hz EA apply to Leg Three Li (足三里 zú sān lǐ, ST-36) and Upper Great Hollow (上巨虛 shàng jù xū, ST-37) acupoints increased vagal activity, whereas 15Hz EA increased sympathetic activity.

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.

The Antioxidative Effect of Electro-Acupuncture in a Mouse Model of Parkinson's Disease

Accumulating evidence indicates that oxidative stress plays a critical role in Parkinson's disease (PD). Our previous work has shown that 100 Hz electro-acupuncture (EA) stimulation at ZUSANLI (ST36) and SANYINJIAO (SP6) protects neurons in the substantia nigra pars compacta from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in male C57BL/6 mice, a model of PD. In the present study we administered 100 Hz EA stimulation at the two acupoints to MPTP-lesioned mice for 12 sessions starting from the day prior to the first MPTP injection. We found that in the striatum of MPTP treated mice 100 Hz EA stimulation effectively inhibited the production of hydrogen peroxide and malonaldehyde, and increased glutathione concentration and total superoxide dismutase activity through biochemical methods. However, it decreased glutathione peroxidase activity via biochemical analysis and did not affect the level of 1-methyl-4-phenylpyridinium in the striatum revealed by high performance liquid chromatography with ultraviolet detection. These data suggest that 100 Hz EA stimulation at ST36 and SP6 has antioxidative effects in the MPTP model of PD. This data, along with our previous work, indicates that 100 Hz EA stimulation at ST36 and SP6 protects the nigrostriatal system by multiple mechanisms including antioxidation and antiapoptosis, and suggests that EA stimulation is a promising therapy for treating PD.

Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model

It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100 Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before a 30-min EA treatment at acupoint Huantiao (GB30) 1 h 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.