• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.881-886
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• 2011

AMPA receptor (AMPAR)s are heterotetrameric structures made up from 4 units (GluR1-4) and are thought to underlie perception of persistent inflammatory pain. Complete Freund's adjuvant (CFA)-evoked inflammation induces synaptic GluR2 internalization, which is initiated by GluR2 phosphorylation, in dorsal horn neurons during the maintenance of CFA-induced hypersensitivity. The present study investigated whether electroacupuncture (EA) stimulation has any effect on GluR2 trafficking by using immunoblot and immunohistochemistry. We examined that CFA-induced dorsal horn GluR2 internalization was attenuated by EA treatment. EA treatment could also decrease the level of pGluR2 regardless of whether CFA injection was administrated or not. In addition, previous studies suggest that microglial cells are increased without morphological change in CFA injected animal. In our study, increases in microglial cells in CFA group were observed, whereas EA with or without CFA-injected group showed similar aspects with normal group. In conclusion, our results indicate that EA might blunt CFA-evoked inflammation by coordinating mechanisms at the upstream step of neuron activation and GluR2 phosphorylation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1285-1290
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• 2007

The present study aims to identify and characterize genes that cause differen genes between non-responders and responders to electroacupuncture (EA) on mechanical allodynia following peripheral nerve injury. Under sodium pentobarbital anesthesia, animals were subjected to unilateral transection of the superior caudal trunk at the level between S1 and S2 spinal nerves. EA stimulation (2Hz, 0.3 ms, 0.2-0.3 mA) was delivered to Zusanli (ST36) for 30 min 2 weeks after the surgery. The degree of mechanical allodynia was assessed quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. The rats, which showed an EA-induced decrease of response frequencies under 10 %, were classified as non-responders and those displaying an EA-induced decrease of response frequencies 20 % or more were classified as responders. Results from oligonucleotide microarray, to which cDNAs from the spinal dorsal horn (DH) were applied, showed that hemoglobin beta chain complex and chondroitin sulfate proteoglycan-5 decreased and limbic system-associated membrane protein increased in the non-responder group, whereas calcium-independent alpha-Iatrotoxin receptor homolog-3 increased in the responder group. These results suggest that The functional abnormality of molecules regulating cell adhesion, intracellular signal transduction and cell differentiation in the spinal DH may be involved in the anti-allodynic effect of EA.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.221-230
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• 2002

Some studies report that electroacupuncture(EA) boost natural killer cell(NK cell) activity. And also it is well known that hypothalamus is deeply related to effects of EA on analgesia. Some reports said that especially lateral hypothalamic area(LHA) is related to splenic NK cell activity. In order to investigate the relation between hypothalamus and effects of EA at ST36 point on NK cell activity of Spraque-Dawley rats. Lesions were made bilaterally at lateral hypothalamic area(LHA). And NK cytotoxities of normal and lesioned rats were measured with 51Cr release immunoassay after EA stimulation for 2 and 14 days. NK cell activity of EA group was significantly higher than sham group at 2nd, 14th day in normal rats. And LHA lesions abolished effects of EA on NK cell activity at 2nd day. But LHA lesions did not affect the effects of EA at 14th days. We also had an evidence that the decrease of NK cell activity was almost recoverd at 14th day. These results strongly suggest that LHA is deeply related to increase of NK cell activity induced by EA.

• Journal of Acupuncture Research
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• v.20 no.1
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• pp.177-190
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• 2003

Objective : This study was intended to investigate the analgesic effects of electroacupuncture(EA) on mechanical allodynia according to the frequency and intensity of EA. Also to know if mechanical allodynia and the analgesic effects of EA is related to the sympathetci nervous system and/or the purinergic system. Methods : mechanical allodynia-induced rats were produced by resecting S1-S2 nerve. The zusanli(ST36) was used for acupoint and the rats were divided into 4 groups. Each group was given different stimuli[low frequency low intensity-EA(LFLI-EA), low frequency high intensity-EA(LFHI-EA), high frequency low intensity-EA(LFHI-EA), high frequency high intensity-EA(HFHI-EA)]. Futhermore, to make sympathectomy6-OHDA and phentolamine were administered intraperitonially and the concentration of norepinephrine(NE) were measured. As a ATP blocker, suramin was applied for this study. Results : Comparing to control group, each of the 4 groups(LFLI-EA, LFHI-EA, HFLI-EA, HFHI-EA) showed a significant reduction of response frequency of mechanical allodynia. LFHI-EA was more effective than that of LFLI-EA. The LFHI-EA group also had longer lasting effects from the stimulation than the other groups. Sympathectomy didn't show any reduction of response frequency of mechanical allodynia.(Each n=6, n=4). Nor did both sympathectomy and ATP block. The response frequency wasn't reduced by sympathectomy or by sympathectomy and ATP block, but was significantly reduced with LFHI-EA Conclusions : These results suggest that EA has a significant analgesic effect on mechanical allodynia which has no connection with NE and/or ATP.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.180-189
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• 2002

Background and Purpose : The hemiplegic upper extremity is affected in many stroke patients, and recovery is often poor. The purpose of this study was to assess the efficacy of electroacupuncture (EA) in enhancing the upper extremity motor and functional recovery of ischemic stroke patients. Subjects and Methods : Forty ischemic stroke patients (the upper extremity Fugl-Meyer motor scale (FM) score lower than 46, lesion location within middle cerebral artery territory) within 2 weeks of stroke onset were randomly allocated to either an EA group that received EA treatment or a control group that received only routine ward care. The EA was applied at Quchi-Shousanli (LI11-LI10), Waiguan-Hegu (TE5-LI4) points on the hemiparetic side six times per week for 4 weeks. The frequency of stimulation was 25-50Hz and the intensity was set at a level sufficient to induce muscle contraction. EA treatment was given for 30 minutes and all patients of both groups received standard rehabilitation program. Outcomes were assessed, in a blind manner, before treatment began and at 4 weeks after treatment, with the FM, the Motor Power score (MP) for shoulder/elbow, and the subsection of the Modified Barthel Index (MBI) for drinking/feeding/dressing upper body/grooming. Results : These 2 groups had comparable clinical characteristics, lesion location, lesion size, and pretreatment impairment scores. By the end of treatment, the EA group showed significantly more improvement than the control group in the subsection of the FM for shoulder/elbow/coordination (6.4 vs. 3.7; P=0.047) and the MP for shoulder/elbow (5.3 vs. 3.3; P=0.008). The subsection scores of the MBI for drinking/feeding/dressing upper body/grooming were not significantly different between two groups. No adverse effects due to treatment were found Conclusion : These results suggest that EA enhances the upper extremity motor recovery of acute stroke patients. However, this study failed to demonstrate any significant functional benefit related with upper extremity. Future study should be carried out in a larger sample size and use the functional outcome measure that is more specific and sensitive to the upper extremity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.407-414
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• 2016

This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

• Korean Journal of Oriental Medicine
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• v.17 no.3
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• pp.105-114
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• 2011

Objectives : The transient inflammation has been demonstrated to alter visceral motor response (VMR) and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia in animal models. The purpose of our study is to compare effects of the different frequencies applied electroacupuncture (EA) on acupoints in acute colitis induced by trinitrobenzenesulphonic acid (TNBS). Methods : In Male Sprague-Dawley rats, weighing 250~400g, a single colorectal administration of TNBS (5mg/kg) was made and electrode for electromyography (EMG) recording were stitched into the external oblique musculature. EA of either ST25 or ST36 were applied and stimulation parameter was modulated as follows: 2, 10, or 100 Hz with intensity of 2 mA and 1 ms pulse duration for 30 min. The balloon was inserted intra-anally and VMR to colorectal distension (CRD) was quantified with an EMG recording system. Results : The VMR increased significantly 3 days after TNBS intra-rectal colonic injection in rats. Both 2 Hz and 10 Hz EA on ST36 suppressed VMR to CRD in the acute colitis model but not 100 Hz. Only 10 Hz EA on ST25 suppressed VMR to CRD in the acute colitis. Conclusions : These data show that 10 Hz EA potently inhibits hypersensitivity of colorectum after TNBS induced colitis.

• Journal of Acupuncture Research
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• v.19 no.3
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• pp.95-106
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• 2002

The present study was designed to investigate the effects of various electroacupuncture(EA) stimulation on NADPH-diaphorase and Neuropeptide Y(NPY) in the cerebral cortex of Sprague-Dawley Rats. We evaluated the changes of NADPH-d-positive neurons using a histochemical method and the changes of NPY-positive neurons using a double labeling immunohistochemical method. The staining intensities of NADPH-d-positive neuron and NPY-positive neurons were assessed in a quantitative fashion using a microdensitometrical method based on optical density by means of an image analyzer. As to frequency, the optical density of NADPH-d-positive neurons of 2Hz-1 time EA group was significantly higher than that of 100Hz-1 time EA group in M1, Cg, and that of 100Hz-3 times EA group was significantly higher than that of 2Hz-3 times EA group in Vi, Au, Cg and Ins. As to treatment-time, the optical density of NADPH-d-positive neurons of 2Hz-1 time EA group was higher than 2Hz-3 times EA group in Vi, Au, Cg and Ins. And in Vi 100Hz-1 time EA group and in M1 100Hz-3 times EA group was more efficient. As to frequency, the optical density of NPY-positive neurons of 2Hz-1 time was significantly higher in Vi, and that of 100Hz-1 EA group was higher in M1. And that of 2Hz-3 times EA group was higher than 100Hz-3 times EA group in Cg. As to treatment-time, the optical density of NPY-positive neurons of 2Hz-1 time EA group was significantly higer than 2Hz-3 times EA in S1, Vi, Au. And that of 100Hz-1 time EA group was significantly higher than that of 100Hz-3 time EA in Cg. The present results demonstrated that EA changes the activity in NO and NPY system in the cerebral cortex of SHR and EA stimulation, like frequency and treatment-time, is of importance for this effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1041-1054
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• 2004

Electroacupuncture (EA) has been reported to increase pain threshold, and to enhance the NK cell activity by up-regulation of IFN-γ and endogenous β-endolphin. For the purpose of understanding the molecular mechanism of EA stimulation, we analyzed the gene expression profile of rat hypothalamus, treated on Zusanli (ST36) with EA, in comparison with control group by oligonucleotide chip microarray (Affymetrix GeneChip Rat Neurobiology U34 Array) and real-time RT-PCR. Sprague-Dawley (S-D) male rats were stimulated at the Zusanli (ST36) acupoint in restriction holder. Simultaneously the control group was given only holder stress without EA stimulation. In order to prove the appropriateness of EA treatment, we measured spleen NK cell activity with standard 51Cr release assay. NK cell activity of EA group was significantly increased comparing to control group. The microarray and PCR results show that EA treatment up-regulates expression of genes associated with 1) nerve growth such as NGF induced factor A and VGF, 2) signal transduction such as 5HT3 receptor subunit, AMPA receptor binding protein and Na-dependent neurotransmitter transporter, and 3) anti-oxidation such as superoxide dismutase and glutathione S-transferase. In addition, the activity of the anti-oxidative enzyme, SOD of hypothalamus, liver and RBC was enhanced compared to that of control. The list of differentially expressed genes may implicate further insight on the mechanism of acupuncture effects.

• Journal of Acupuncture Research
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• v.19 no.6
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• pp.111-124
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• 2002

A line of study reported that electroacupuncture(EA) modulate natural killer cell(NK Cell) activities. One report suggested that EA enhanced splenic interferon-gamma($IFN-{\gamma}$), interleukin-2(IL-2), and NK cell activity in Sprague-Dawley rats. Another study suggested that $IFN-{\gamma}$ mediates the up-regulation of NK cell activity, and endogenous ${\beta}$-endorphin secretion also play a role in the up-regulation of NK cell activity induced by EA stimulation. In order to better understand the molecular regulation underlying the activation of NK cell induced by EA, we have utilized cDNA microarray to elucidate how EA alters program of gene expression of spleen in rats. First, we divided three groups, group I was EA group treated with EA in restriction holder, group II was sham group with only holder stress, and last group III was control group with no treatment. We measured NK cell activity after EA stimulation three times for 2 days using $^{51}Cr$ release assay. Second, Biotin-labeled cDNA probes synthesized from EA group and sham group, were competitively hybridized to the microarray that contained variable genes. Such high-throughput screening has identified a number of EA-responsive gene candidates. Of these, we found that EA induced a subset of genes of genes that functionally could modulatory effects on NK cell activity. Genes(vascular cell adhesion molecule-1, protein-tyrosine kinase, CD94 mRNA) related to boost NK cell activity, were increased by EA And, genes(protein-tyrosine-phospatase mRNA, protein-tyrosine phosphatase(SHP-1) mRNA) related to inhibit NK cell activity, were decreased by EA. These EA-responsive genes may provide key insights from which to understand mechanisms of activation of NK cell induced by EA.