research article electroacupuncture versus moxibustion for...

Research ArticleElectroacupuncture versus Moxibustion for Irritable BowelSyndrome A Randomized Parallel-Controlled Trial

Yin Shi1 Yue-Hua Chen2 Xiao-Jun Yin1 An-Qi Wang1 Xing-Kui Chen3 Jin-Hua Lu4

Rong Ji1 Chun-Hui Bao1 Jie Sun1 Ji-Meng Zhao1 and Huan-Gan Wu1

1Department of Medical Clinic Yueyang Chinese and Western Medicine Integrated HospitalShanghai University of Traditional Chinese Medicine Shanghai 200437 China2Department of Gastroenterology Jinhua Municipal Central Hospital Jinhua 321000 China3Department of Acupuncture and Moxibustion Jinhua Municipal Central Hospital Jinhua 321000 China4Department of Medical Imaging Jinhua Municipal Central Hospital Jinhua 321000 China

Correspondence should be addressed to Huan-Gan Wu wuhuanggan126com

Received 19 May 2015 Accepted 13 July 2015

Academic Editor Lisa A Conboy

Copyright copy 2015 Yin Shi et al This is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Objective To compare the impacts of electroacupuncture (EA) and mild moxibustion (Mox) on patients with irritable bowelsyndrome (IBS) Method Eighty-two IBS patients were randomly allocated into EA group (119899 = 41) and Mox group (119899 = 41) andreceived corresponding interventions for four weeks Before and after the treatment the Visual Analogue Scale for Irritable BowelSyndrome (VAS-IBS) was used to evaluate the gastrointestinal symptoms and mental well-being and the expression of serotonin(5-hydroxytryptamine 5-HT) 5-HT

3receptor (5-HT

3R) and 5-HT

4receptor (5-HT

4R) in sigmoid mucosal tissue were detected

Results Both EA and Mox can radically improve the total VAS-IBS score (119875 lt 005) and EA was found to be more effective inameliorating the symptom of constipation while Mox was found to be more effective in ameliorating the symptom of diarrhoeaThe abnormal expressions of 5-HT 5-HT

3R and 5-HT

4R in both groups were significantly improved after the treatments (all

119875 lt 005) and EAwas superior toMox in regulating the abnormally decreased 5-HT4R expression in IBS patients with constipation

(119875 lt 005) Conclusion Electroacupuncture and mild moxibustion were both effective in improving IBS symptoms and modulateabnormal expressions of 5-HT 5-HT

3R and 5-HT

4R in the colonic tissue

1 Introduction

Irritable bowel syndrome (IBS) is a chronic recurrentfunctional gastrointestinal (GI) disorder [1] characterizedby lower abdominal pain andor discomfort accompaniedby altered defecation without corresponding evidence ofstructure abnormalities [2] The general prevalence of IBSaround the world was approximately 11 [3] and suggesteda female predominant tendency [4] The first presentation ofIBS patient to a physician is mostly between the age of 30and 50 years and the symptomsrsquo onset is closely related topsychological stress [5] Though IBS is unlikely to developinto serious organic disease or has an impact on mortalityit can greatly compromise patientsrsquo quality of life and hindertheir normal social function [6]

Treatments of IBS range from pharmacological treat-ments (linaclotide antispasmodics 5-HT

3antagonists etc)

[7] to psychological therapies (cognitive behavioural ther-apy and hypnotherapy) [8] However current medicationsfor IBS were targeted on specific dominant symptom [9]while IBS patients always suffer from a group of coexistingcomplains Psychological therapies were considered lack ofcost efficiency comparing to its moderate severity Thereforethe most urgent and intractable problem for clinical gas-troenterologists to deal with is to develop a both effectiveand economical treatment method which could cope withdifferent symptoms of IBS

In recent decades complementary and alternativemedicine especially Chinese Medicine represented byacupuncture has been brought into researchersrsquo sights for

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 361786 12 pageshttpdxdoiorg1011552015361786

2 Evidence-Based Complementary and Alternative Medicine

its substantial therapeutic potency in managing variety offunctional disorders and pain syndromes

So far a large number of experimental studies have pro-vided robust evidence to support the efficiency of acupunc-turemoxibustion in IBS treatment and to illuminate themechanism underlying their multifunction and multitargeteffects [10] Meta-analysis on randomized sham-controlledtrials has verified the therapeutic efficiency of acupunc-ture in IBS management [11] and further suggested itssuperiority in achieving GI symptoms amelioration whencomparing to conventional pharmacological therapies [12]Electroacupuncture is a modern adaptation of traditionalChinese hand-manipulated acupuncture By adding a directelectrical current to needles the stimulation to the acupointscan be amplified and therefore improve its therapeutic effectElectroacupuncture was reported to have positive effecton modulating gastrointestinal motility secretion [13] painsensation [14] and brain-gut interaction [15] On the otherhand as another highly efficient Chinese Medicine therapybasing on the Meridians and AcupointsTheory moxibustionhas drawn much less attention than acupuncture despiteits equally robust effectiveness in clinical practice Existingclinical studies concerning moxibustion therapy on IBS werebarely persuasive due to their poor adherence to standardrandomized controlled trials (RCTs) criterion and conse-quently high risk of bias [16]

For this reason we designed this randomized parallel-controlled trial strictly following the CONSORT 2010 state-mentrsquos guideline [17] in order to provide credible clinical evi-dence to support the application of acupuncturemoxibustionin IBS treatment Also we expected that this study might ini-tially prove the distinguishing effects of electroacupunctureandmildmoxibustion on different symptoms of IBS and thuscan help clinicians to select the optimal treatment based onpatientsrsquo individual circumstances

2 Materials and Methods

21 Study Design This study was a parallel randomized con-trolled trial approved by the Chinese Clinical Trial RegisterCentre (registration number ChiCTR-TRC-11001349) Allthe participants were randomly allocated into EA group orMox group by a 1 1 ratio

211 Participants All participants were recruited from out-patients of the Department of Gastroenterology in Jin-hua Municipal Central Hospital between January 2012 andSeptember 2013

Eligibility criteria for participants were adults (aged 18ndash65 years) with symptoms consistent with IBS in accordancewith Rome III diagnostic criteria [9] who were willing toparticipate in the study and sign the informed consentPatients were to have had symptoms for at least three monthsand had diarrhea orand constipation occurring for at least 2daysweek Other physical diseases including cerebral vesselsdiseases liver or kidney diseases disorders of hematopoieticsystem or structural disease on the intestines were requiredto be absent or inactive Exclusion criterion also includesformal diagnosis of psychiatric disease receiving of any

medication aiming to treat IBS or thatmay induce IBS-relatedsymptomsmoxibustion or acupuncture treatment aiming forthe treatment of IBS within 2 weeks ahead of the treatmentsession and women during pregnancy or nursing

All the treatment interventions were performed byqualified and experienced acupuncture and moxibustionpractitioners from Department of Medical Clinic YueyangChinese and Western Medicine Integrated Hospital affiliatedto Shanghai University of Traditional ChineseMedicine whohave the Chinese Medicine practitioner license from theMinistry of Health of China

212 Randomization and Blinding Adopting the SNOSE(sequentially numbered opaque sealed envelopes) method[18] simple concealed randomization was carried out toeliminating possible selection bias [19] Participants wereallocated into electroacupuncture (EA) group or mild moxi-bustion (Mox) group on 1 1 bases

To avoid bias and intentional manipulation as far aspossible the initial symptom evaluation electroacupunctureor mild moxibustion intervention posttreatment symptomevaluation and data analysis were performed by differentpractitioners who were blinded to treatment arm assign-ments throughout the study Moreover the practitionerwho performed the electroacupuncture or mild moxibustiontreatment was not allowed to exchange any idea with theparticipants concerning their present symptoms or medicalhistory during the whole treatment session

This study has been approved by Ethics Committee ofYueyang Hospital of Integrated Traditional Chinese andWestern Medicine Shanghai University of Traditional Chi-nese Medicine of the research project (Approved number2010-08) All patients have been notified of their rights andsigned an informed consent

22 Interventions Each patient received a total of 24 EAMoxtreatment sessions once a day over four weeks suspendedon each Sunday Acupoints selection and EAMox treatmentwere performed according to Chinese Medicine theory Theacupoints ST-25 (Tianshu) and ST-37 (Shangjuxu) on bothsides of body were located following the national standard ofacupoint location GB-12346-90 [20]

For the EA group after 3 cm radius around the acu-points was sterilized with 75 ethanol disposable stainlesssteel needles (030 times 40mm Hwatuo Suzhou China) wereinserted into the skin to a depth of 20ndash25mm Twirling-rotating method was then applied to acquire a dull needlingsensation called ldquoDe Qirdquo After ldquoDe Qirdquo the electrical leadsof the HAN Acupoint Nerve Stimulator (HANS Model LH100A TENS Nanjing China) were connected to each needlewith stimulation frequency of 2Hz and intensity of 30mAfor 30min

The Mox group received mild moxibustion on the samefour acupoints for 30min Moxa rolls (18 times 200mm HwatuoSuzhou China) with one end ignited were hold vertically tothe skin 2-3 cm above the acupointsThe surface temperatureof the acupoints wasmaintained at 46∘Cplusmn 1∘Cby adapting thedistance between themoxa roll and the acupoint For every 3-4min the practitioners would flick the moxa ash into a trayin case the ash falls onto the skin and burns the participant

Evidence-Based Complementary and Alternative Medicine 3

Table 1 VAS-IBS questionnaire

Items Score rangeGastrointestinal symptoms

Abdominal pain 0ndash100Diarrhoea 0ndash100Constipation 0ndash100Bloating and flatulence 0ndash100Vomiting and nausea 0ndash100

Mental healthPerception of mental well-being 0ndash100

Quality of lifeGI symptom influencing daily life 0ndash100

Total score 0ndash7000 represents very severe problems and 100 represents absence of problemsVAS-IBS Visual Analogue Scale for Irritable Bowel Syndrome GI gastroin-testinal

23 Outcome Measures

231 Primary Outcome Measure The prespecific primaryoutcome measure is the total score of the Visual AnalogueScale for Irritable Bowel Syndrome (VAS-IBS) [21 22] TheVAS-IBS was a self-rating questionnaire developed basingon the widely used Visual Analogue Scale (VAS) to measuretreatment response of gastrointestinal symptoms as well asmental well-being in patients with IBS As exhibited inTable 1 VAS-IBS questionnaire contains seven items coveringfive most common gastrointestinal symptoms (abdominalpain diarrhoea constipation bloating and flatulence andvomiting and nausea) mental well-being and the impact ofIBS symptoms on daily life The score for each item rangesfrom 0 (most severe) to 100 (absent of symptom) resultingin a total score between 0 and 700 This questionnaire wastranslated and modified into Chinese in line with practicaldemand

232 Secondary Outcome Measure The secondary outcomemeasures are the five gastrointestinal symptoms from theVAS-IBS The improvement or aggravation of each singlesymptom was demonstrated by the differential of scoresbefore and after the interventions By comprising thesedifferentials the therapeutic superiority of EA and Moxtreatments on different gastrointestinal symptomswas able tobe evaluated

233 Immunohistochemistry Before and after the treatmentall participants received colonoscopy with or without intra-venous anaesthesia and sigmoid colon tissues were takento detect the expression of 5-HT 5-HT

3R and 5-HT

4R

At the same time 10 sigmoid colon tissue samples fromhealthy volunteers were taken as normal control (NC) Allsamples were first fixed in 10 neutral-buffered formalinand then tissues vertical to intestinal diameter were selecteddehydrated and embedded in paraffin After being sliced into4 120583-thick paraffin sections and baked at 58∘C for 24 h theexpression of 5-HT 5-HT

3R and 5-HT

4R in colon tissue

was detected by immunohistochemical stainingThe sections

were exposed to 001MCB pH 60 microwaved at 30power for 20min for heat fixation and cooled to roomtemperature The sections were washed 3 times with PBSfor 3min and exposed to 03 H

2O2for 20min at room

temperature to inhibit endogenous peroxidases Following afinal PBS wash (3 times 3min) the samples were exposed to 20normal goat serum and incubated for 30min Antibodieswere added dropwise (5-HT 1 100 5-HT

3R 1 50 and 5-

HT4R 1 80 SantaCruz CA) and the sectionswere incubated

at 37∘C for 2 hours The sections were washed with PBS 3times for 3min incubated in HRPR reagent at 37∘C for30min and PBS washed 3 times for 3minThe sections werethen incubated in DAB chromogenic reagent for 8 to 12minand dyed with hematoxylin lining and blue in the presenceof hot water After drying the sections were wrapped withneutral gum A semiquantitative analysis of the staining wasperformed using the MIQAS medical image quantitativeanalysis system (Shanghai Qiuwei Biomedical TechnologyCompany) Positive results were indicated by the presenceof brown or tan particles in the stained colonic tissue cellsIn each slice three positive areas were counted and assessedfor optical density (OD) in a high power field to calculate animmunohistochemical positive index (IHC index = positivearea times ODtotal area) for 5-HT 5-HT

3R and 5-HT

4R

24 Statistical Methods Statistical analyses were performedusing SPSS 180 (SPSS Inc Chicago Illinois) Normallydistributed continuous variables were expressed as mean plusmnSD while abnormally distributed continuous variables wereexpressed as mean the 25th and the 75th percentiles Cate-gorical variableswere showed as frequencies andproportionsFor normally distributed continuous variables differenceswithin groups before and after the treatment sessions werecompared by paired-samples 119905-test and differences betweengroups were compared by two independent samples 119905-testAbnormally distributed continuous variables were comparedby Wilcoxon rank sum tests Pearsonrsquos 1205942 test was usedfor comparisons of categorical variables Differences wereconsidered statistically significant if 119875 lt 005

3 Results

31 Participant Flow Figure 1 is a diagram illustrating theparticipant flow of the study From January 2012 to Septem-ber 2013 89 participants were recruited of which 7 wereexcluded leaving 82 who were randomly allocated into EAgroup orMox groupThemajority of eligible participants (119899 =82 9213) completed the trials while 4 (488) withdrawnthe treatments midway

Scores of the VAS-IBS questionnaire were measuredimmediately prior to the first treatment session and again atthe point the last treatment session was finished In the enddata from 78 participants were included for the final analysis

32 Baseline Data Baseline demographic data include gen-der and age disease duration previous medication VAS-IBS total score and IBS subtype distribution in each group(Table 2) No significant differences were demonstrated in


Allocation

Analysis

Enrollment Assessed for eligibility (n = 89)

Randomized (n = 82)

Excluded (n = 7)

Not meeting inclusion criteria (n = 4)

Declined to participate (n = 1)

Other reasons (n = 2)

Allocated to Mox group (n = 41)

Received allocated intervention (n = 40)

Intermediate withdrawal (n = 1)

(evection = 1)

Allocated to EA group (n = 41)



(adverse event = 1 lacking curativeeffect = 1 and disobeying the trial = 1)

Analysed (n = 38)

Excluded from analysis (n = 0)

(IBS-D = 17 IBS-C = 17 and IBS-AM = 4)

Analysed (n = 40)



Figure 1 Flow diagram of the study Flow gram for the trial EA electroacupuncture Mox mild moxibustion

these parameters between the two treatment groups (119875 lt001)

33 Outcomes and Estimation

331 Primary Outcome Measure The participantsrsquo overallperception of their gastrointestinal symptoms and theirsubjective mental well-being was translated into quantitativeparameters by the VAS-IBS total score Within-group andbetween-group comparison were made to evaluate treatmentresponses to each interventionmethod A remarkable declinein VAS-IBS total scores was identified after the whole treat-ment sessions in both EA group and Mox group (119875 lt 001)The improvement of VAS-IBS total score in Mox group wasslightly greater than that of EA group however between-group difference showed no statistical significance (Table 3)

332 Secondary Outcome Measure The five items from theVAS-IBS questionnaire concerning gastrointestinal symp-toms namely abdominal pain diarrhoea constipationbloating and flatulence and vomiting and nausea wereutilized as secondary outcome measures to assess the impactof EA and Mox intervention on each specific symptoms InEA group all the five symptoms were significantly improvedafter the treatment (119875 lt 001) Between-group comparisonsof the change in score of each symptom were illustratedin Figure 2 Differences in therapeutic effect of EA and

Mox interventions on the symptoms of abdominal painbloating and flatulence and vomiting and nausea were barelynoticeable However EA demonstrated a significant grateradvantage in ameliorating the symptomof constipation in IBSparticipants (2429 versus 527 119875 lt 001) Conversely Moxwas significantly more efficient in ameliorating the symptomof diarrhoea (2542 versus 655 119875 lt 001)

333 5-HT Expressions before and after the TreatmentFigure 3(a) showed the immunohistochemical positive areaof 5-HT expressions in IBS patientsrsquo sigmoid colon tissuesbefore and after the EA and Mox treatments Before thetreatment (Figure 3(b)) the 5-HT expressions in the colonictissue of the EA and Mox groups were both significantlyhigher than that of the NC group (20437plusmn6197 and 19893plusmn6530 versus 7867 plusmn 1388 resp both 119875 lt 001) while nosignificant difference was observed between the EA andMoxgroups (119875 = 0905 119875 gt 005)

After the treatment (Figures 3(c) and 3(d)) the abnor-mally increased expressions of 5-HT in the colonic tissue ofthe EA and Mox groups were both significantly decreased(12213plusmn5009 versus 20437plusmn6197 and 12321plusmn5006 versus19893plusmn6530 resp both 119875 lt 001) However by comparingthe differentials in 5-HT expressions before and after thetreatments no significant difference was observed betweenthe EA andMox groups (minus8223plusmn3357 versusminus7572plusmn3997119875 = 0190 119875 gt 005)


Table 2 Baseline demographic characteristics and VAS-IBS totalscores

Parameter Group EA(119899 = 41)

Group Mox(119899 = 41)

GenderFemale () 6098 6529Male () 3902 3471

Ageyr (mean (min max)) 3945 (19 61) 4026 (20 64)

Course of diseaseyr (mean plusmn SD) 647 plusmn 384 728 plusmn 544

Current medicationYes () 0 (0) 0 (0)No () 41 (10000) 41 (10000)

VAS-IBS total score(mean plusmn SD) 25349 plusmn 4593 25024 plusmn 4108

IBS subtypeIBS-D () 17 (4146) 18 (4390)IBS-C () 19 (4634) 17 (4146)IBS-AIBS-M () 5 (1220) 6 (1463)

Visual Analogue Scale for Irritable Bowel Syndrome EA electroacupunc-ture Mox moxibustion SD standard deviation IBS-C irritable bowelsyndrome with constipation IBS-D irritable bowel syndrome with diar-rhoea IBS-M mixed irritable bowel syndrome (with both diarrhoea andconstipation gt25 of bowel movements) and IBS-A alternating irritablebowel syndrome (bowel habits often vary over time)

334 5-HT3R Expressions before and after the TreatmentFigure 4(a) showed the immunohistochemical positive areaof 5-HT

3R expressions in IBS patientsrsquo sigmoid colon tissues

before and after the EA andMox treatments Before the treat-ment (Figure 4(b)) the 5-HT

3R expressions in the colonic

tissue in the EA and Mox groups were both significantlyhigher than the NC group (7975 plusmn 4272 and 9008 plusmn 5070versus 4519 plusmn 684 both 119875 lt 001) while no significantdifference was observed between the EA and Mox group(7975 plusmn 4272 versus 9008 plusmn 5070 119875 = 0472 119875 gt 005)

After the treatment (Figures 4(c) and 4(d)) the abnor-mally increased 5-HT

3R expressions in the colonic tissue of

the EA and Mox groups were both significantly decreased(6698 (5001 10396) versus 3963 (2740 6119) and 7273(4941 11509) versus 5223 (3918 7060) resp both 119875 lt001) However by comparing the differentials in 5-HT

3R

expressions before and after the treatments no significantdifference was observed between the EA and Mox groups(119875 = 0335 119875 gt 005)



before and after the EA andMox treatments Before the treat-ment (Figure 5(b)) between-group comparison among theEA Mox and NC groups showed no significant differencesin 5-HT

4R expressions in the colonic tissue (3997 (3803

4687) and 3718 (1793 6401) versus 4127 (2189 5987) all119875 gt 005) However the tendency of dispersion in the EA andMox groups was much greater than that of the NC group

After the treatment (Figures 5(c) and 5(d)) there wereno significant differences in the expression of 5-HT

4R in the

EA group before and after the treatment (3718 (1793 6401)versus 3683 (3105 4557) 119875 = 0446 119875 gt 005) whilethe expression of 5-HT

4R in the Mox group was significantly

decreased after the treatment (4127 (2189 5987) versus3414 (2427 4211) 119875 = 0002 119875 lt 001) By comparingthe differentials in 5-HT

4R expressions before and after the

treatments no significant difference was observed betweenthe EA and Mox groups (119875 = 0079 119875 gt 005) Howeverthe absolute values of these differentials showed that changesin 5-HT

4R expressions of the EA group were significantly

greater than that of the Mox group (1521 (757 2020) versus589 (277 1645) 119875 = 0015 119875 lt 005)

336 SubgroupAnalysis ofDifferent IBS Subtypesrsquo Differentialsin 5-HT4R Expression before and after the Treatment Table 4demonstrated 5-HT


each IBS subtype before and after the treatments in the EAand Mox groups Before the treatments 5-HT

4R expressions

in each IBS subtype showed no significant difference in theEA and Mox group (119875 = 0574 0189 0610 for IBS-D IBS-Cand IBS-AM resp all 119875 gt 005)

In IBS-D patients 5-HT4R expressions in the colonic

tissue of the EA and Mox groups were both significantlyhigher than that of the NC group (6556 plusmn 1582 and 6288 plusmn1200 versus 4207plusmn604 both119875 lt 001) After the treatmentsthese abnormally increased 5-HT

4R expressions were both

significantly decreased (both 119875 lt 001 versus before thetreatment) However by comparing the differentials in 5-HT4R expressions of IBS-D patients before and after the

treatments no significant difference was observed betweenthe EA and Mox groups (119875 = 0385 119875 gt 005)

In IBS-C patients 5-HT4R expressions in the colonic

tissue of the EA andMox groupswere both significantly lowerthan that of the NC group (1837 plusmn 783 and 2242 plusmn 969versus 4207plusmn604 both119875 lt 001) After the treatments theseabnormally increased 5-HT

4R expressions were both signifi-

cantly decreased (both 119875 lt 001 versus before the treatment)At the same time the increase of 5-HT

4R expression in the

EA group was found to be significantly greater than that ofthe Mox group (119875 lt 001)

In IBS-AM patients between-group comparison showedno significant differences in 5-HT

4R expressions in the

colonic tissue between any two of the three groups (3707 plusmn819 versus 3262 plusmn 1481 versus 4207 plusmn 604 all 119875 gt 005)After the treatments within-group comparison showed nosignificant difference in the 5-HT

4R expression of the EA

group (119875 = 0456 versus before the treatment) and a sig-nificant decrease in the 5-HT

4R expression of the EA group

(119875 = 0015 versus before the treatment 119875 lt 005) Howeverby comparing the differentials in 5-HT

4R expressions of IBS-

AM patients before and after the treatments no significantdifference was observed between the EA and Mox groups(119875 = 0624 119875 gt 005)

34 Treatment Adherence Thirty-eight out of 41 participants(9268) in the EA group completed the trial in comparisonto 40 out of 42 (9756) in the Mox group Among the three


Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)

Figure 2 Secondary outcome measure of the VAS-IBS score Secondary outcome changes in VAS-IBS gastrointestinal symptom scores atbaseline and after treatment (a) Abdominal pain (b) diarrhoea (c) constipation (d) bloating and flatulence and (e) vomiting and nauseaEA electroacupuncture Mox mild moxibustion


Table 3 IBS-VAS total score before and after the treatment sessions

Group 119899 Before treatment (mean plusmn SD) After treatment (mean plusmn SD) DifferentialsEA 38 25366 plusmn 4602 36361 plusmn 7571998771 10995Mox 40 25017 plusmn 4119 36200 plusmn 6514998771 11183998771119875 lt 001 versus before the treatment Visual Analogue Scale for Irritable Bowel Syndrome EA electroacupuncture Mox moxibustion and SD standard

deviation

Immunohistochemistry for 5-HT expressions (IHC staining times20)

The EA group The Mox groupBefore treatment After treatment Before treatment After treatment

(a)

5-HT expression before treatmentMoxEANC

350

300

250

200

150

100

50

0

(b)

5-HT expression in the EA groupEA

350

300

250

200

150

100

50

0

After treatment Before treatment

(c)

5-HT expression in the Mox groupMox

350

300

250

200

150

100

50

0


(d)

Figure 3 Comparison of 5-HT expressions before and after treatment (a) Immunohistochemistry for 5-HT expressions in sigmoid mucosatissue of IBS patients before and after treatments in the EA and Mox groups (IHC staining times20) Arrows represent immunohistochemistrypositive expressions (b) 5-HT expressions in the EA andMox groups before treatment comparing to theNCgroup (c) 5-HT expression beforeand after the treatment in the EA group (119875 lt 001) and (d) 5-HT expression before and after the treatment in the Mox group (119875 lt 001) NCthe normal control group EA the electroacupuncture group and Mox the mild moxibustion group

participants who failed to complete the treatment sessions inthe EA group one disobeyed the trial for taking medicationaiming for the treatment of IBS one lacked curative effectand asked to withdraw voluntarily only one was afraid ofacupuncture and refused to continue the trial during the firsttreatment session The one withdrawn participant in Moxgroup was due to long time evection

35 Safety Control and Adverse Events To minimize theoccurrence rate of adverse events a care provider was

specially assigned to explain the dos and donrsquots regarding EAand Mox treatments before the treatment started Emphasishas been drawn on avoiding the state of hunger fatigueand drunkenness Warm water and candy bars were pre-pared in the case that participants developed a symptom ofacupuncture fainting All the treatments were applied afterthe participantwas lying on the bed in a comfortable position

Two participants in the EA group (526) and two in theMox group (5) reported discomfort such as mild sicknesssweating or dizziness during the treatment sessions Most



Immunohistochemistry for 5-HT3R expressions (IHC staining times20)

(a)

MoxEANC

250

200

150

100

50

0

29 17

5-HT3R expression before treatment

(b)

EA

250

200

150

100

50

0

29

29


5-HT3R expression in the EA group

(c)

Mox

250

200

150

100

50

0

17


5-HT3R expression in the Mox group

(d)

Figure 4 Comparison of 5-HT3R expressions before and after treatment (a) Immunohistochemistry for 5-HT

3R expressions in

sigmoid mucosa tissue of IBS patients before and after treatments in the EA and Mox groups (IHC staining times20) Arrows representimmunohistochemistry positive expressions (b) 5-HT

3R expressions in the EA and Mox groups before treatment comparing to the NC

group (c) 5-HT3R expression before and after the treatment in the EA group (119875 lt 001) and (d) 5-HT

3R expression before and after the

treatment in the Mox group (119875 lt 001) NC the normal control group EA the electroacupuncture group and Mox the mild moxibustiongroup

incidents occurred at the first session and were relieved afterresting All these four participants continued and finished thetrial

4 Discussion

41 Acupuncture and Moxibustion in IBS Management IBSis a functional disorder whose leading symptom is diarrhoeaor constipation-associated abdominal pain or discomfortBy the nature of altered bowel habits IBS is classified intosubtypes including IBS-C irritable bowel syndrome withconstipation IBS-D irritable bowel syndrome with diar-rhoea IBS-M mixed irritable bowel syndrome (with bothdiarrhea and constipation gt25 of bowel movements) andIBS-A alternating irritable bowel syndrome (bowel habitsoften vary over time) [1] This classification was originally

designed to help selecting patients for treatments or clinicaltrials targeting a specific bowel pattern However this singlesymptom oriented strategy was largely disabled by the rapidlyfluctuating symptoms in IBS patients [23] By contrast thisunpredictable characteristic of symptoms is barely problem-atic in acupuncture andor moxibustion practice becauseof these two therapies focusing on the principle cause ofa disease rather than some specific symptoms The resultshowed that although the symptoms of participants werevaried and their IBS subtypes were different most of themwere well responded to their allocated treatmentWhat needsto be noticed is that this symptom amelioration made beEAMox was not confined to one or some specific symptomsbut rather universal At the point that the treatment sessionwas ended a majority of participant reported that most oftheir IBS-related symptoms were obviously relived but theimprovement of each symptom was not simultaneous In




(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in



group (c) 5-HT4R expression before and after the treatment in the EA group and (d) 5-HT

4R expression before and after the treatment in

the Mox group (119875 lt 001) NC the normal control group EA the electroacupuncture group and Mox the mild moxibustion group

most case abdominal pain and distension sensation were thefirst improved symptoms simply after one or two sessions Bycontrast the improvement of diarrhoea orand constipationmeasured by defecation frequency and stool form was rathera gradual procedure

The most intriguing finding in this study is the differentadvantage of EAMox therapy in IBS treatmentThough theirefficiency in improving the VAS-IBS score had no significantdifference EA appeared to be more potent when dealingwith constipation while Mox demonstrated the advantage incoping diarrhoea

In recent years researchers have gained concrete evidenceto support the efficiency of these ancient therapies and weremaking constant endeavour to illuminate their functioningmechanisms including affecting visceral sensation motilityandor brain-gut interactions [24ndash26] At the same timethe different mechanisms of these two therapies were alsoidentified by a large amount of researches

Electroacupuncture (EA) is a combination of electricalimpulse and acupuncture marked by its outstanding effi-cacy in alleviating both sensory and affective inflammatorypain [27] including visceral neuropathic pain in IBS andimproving visceral hyperalgesia [28] toward visceral stimuliAt the same time it can also promote gastrointestinalmotility[29] in patients with constipation In the current researchwe actually observed the superiority of EA in alleviatingthe symptom of constipation after treatment comparing toMox Those participants who originally complained aboutprolonged defecation straining andor feeling of incompleteevacuation reported a notable improvement in bowel habitsand stool form Some participants from the EA groupreported subjective feeling of accelerated gastrointestinalperistalsis and increased appetite during the treatment ses-sions also consequently weight gain

As to moxibustion former study showed that the thermalstimulation of moxibustion to the paraumbilical region can


Table 4 Subgroup analysis of different IBS subtypesrsquo differentials in 5-HT4R expression before and after treatment (mean plusmn SD)

Group IBS subtypes 119899 Before treatment After treatment Differentials

EAIBS-D 17 6556 plusmn 1582 4703 plusmn 1021998771 minus1853 plusmn 777IBS-C 17 1837 plusmn 783 3239 plusmn 878998771 1403 plusmn 641lowast

IBS-AM 4 3707 plusmn 819 3503 plusmn 768 minus204 plusmn 478

MoxIBS-D 18 6288 plusmn 1200 4199 plusmn 870998771 minus2088 plusmn 802IBS-C 17 2242 plusmn 969 2557 plusmn 1031998771 314 plusmn 197

IBS-AM 5 3262 plusmn 1481 2867 plusmn 1323 minus394 plusmn 213998771119875 lt 001 versus before the treatment 119875 = 0015 versus before the treatment 119875 lt 005 lowast119875 lt 001 versus the Mox group EA electroacupuncture Mox

moxibustion SD standard deviation IBS-C irritable bowel syndrome with constipation IBS-D irritable bowel syndrome with diarrhoea IBS-M mixedirritable bowel syndrome (with both diarrhoea and constipation gt25 of bowel movements) and IBS-A alternating irritable bowel syndrome (bowel habitsoften vary over time)

increase blood flow of superior mesenteric artery [30] andrelieve abdominal pain due to vasospasm Neverthelessrecent study on mice suggested the potential of moxibus-tion in antibacterial infection by activating macrophageautophagy [31] In this study comparing between Mox andEA has demonstrated the significant superiority of Mox inimproving diarrhoea in IBS especially in participants whosediarrhoea often occurs after the intake of cold drinkfood orwhen exposed in cold environmentsThis kind of participantswas usually more sensitive to Mox therapy because theirhypersensitivity to cold stimuli could be principally improvedby the warm stimulation of Mox

42 Serotonin and Its Receptors in Pathophysiology and Treat-ment of IBS The interaction between the central nervoussystem (CNS) and enteric nervous system (ENS) through var-ious neurotransmitters and hormones composes a complexbidirectional signalling system called brain-gut axis [32] 5-HT as one of the brain-gut peptides locating in both CNSand ENS plays a predominant role in the pathophysiology ofIBS [33] Through interaction with different receptors 5-HTcontrols the intestinal motility and secretion Abnormalitiesin 5-HT signalling system may affect the sensory motor andsecretory function of the digestive system result in gastroin-testinal dysmotility visceral hypersensitivity and infectionand further influence patientsrsquo mental condition [34]

The signal transmission between the CNS and ENSis predominantly mediated by 5-HT

3R [35] and the sig-

nificantly lowered pain threshold and hyperactivity of thegastrointestinal smooth muscles in IBS patients are closelyrelated to the increased 5-HT

3R in gastrointestinal tract [36]

Previous studies have showed that both EA and Mox wereefficient in enhancing the pain threshold and downregulatingthe abnormally increased 5-HT and 5HT

3R expressions

therefore relieving hypersensitivity [37ndash39] The currentresearch found that before treatment IBS patients exhibitedan elevated expression of 5-HT and 5-HT

3R in colon tissue

compared to healthy controls Following EA and Mox treat-ment the expression of 5-HT and 5-HT

3R in colon tissue was

significantly decreased along with the significant alleviationof abdominal pain bloating or abdominal discomfortTheseresults confirmed that overexpression of 5-HT and 5-HT

3R

expressions in the colon tissue of IBS patients is closely relatedto visceral hypersensitivity and further suggested that both

EA and Mox treatments may relieve symptoms result fromvisceral hypersensitivity by downregulating of 5-HT and 5-HT3R expressions5-HT4R is another important receptor in regulating

gastrointestinal function By acting at 5-HT4R located in

gastrointestinal mucosa and smooth muscles 5-HT is ableto release transmitters in prokinetic reflex pathways andtherefore promote and maintain propulsive intestinal motil-ity [40] In clinical practice 5-HT

4R agonists are widely

used in the management of IBS-C to promote gastrointesti-nal motility and attenuate visceral pain [41] The currentresearch found that comparing to the healthy controls 5-HT4R expression in the colonic mucosa was significantly

lower in IBS-C patients and significantly higher in IBS-D patients suggesting that the abnormal expression of 5-HT4R is involved in gastrointestinal motility disorder These

findings suggested that EA therapy can significantly promoteintestinal peristalsis of IBS-C patients and effectively alleviatesymptoms including defecation frequency difficulty in defe-cation and constipation and it might work through increas-ing 5-HT

4R expression in the colonic mucosa Conversely

moxibustion therapy had no apparent effect on 5-HT4R

expression in the colonic mucosa of C-IBS patients and thedefecation frequency and constipation were not improved inthese patients

43 Strength and Limitation Currently many studies havebeen devoted to prove the clinical feasibility and efficiency ofacupuncturemoxibustion in treating IBS However despitethe encouraging evidence from animal experiment mostfindings from these clinical studies were much less satis-factory and persuasive largely because of their questionablerandomization process and poorly standardized interventionprocedure [12] In this study we have designed and con-ducted the study according to the standard RCT principle inCONSORT 2010 statement [17] and CONSORT extension foracupuncture During the whole procedure we make a greatdeal of efforts to make sure the randomization and blindingwere obeyed although double-blind trial is very difficult toachieve in trials involving acupuncturemoxibustion inter-vention because practitioners need to ask the patientrsquos feelingto make sure the acquisition of De Qi sensation and thisspecific sensation is closely related to the therapeutic effect ofthese therapiesWehope that our findings herewould provide


the initial reliable scientific evidence for the clinical utilityof acupuncturemoxibustion in IBS management Also thedifferent finding in EA and Mox treatment might helpthe acupuncturemoxibustion clinicians to select a moreappropriate therapy for each IBS individual basing on theirdiarrhoeaconstipation symptoms

Conflict of Interests

The authors declare no conflict of interests

Authorsrsquo Contribution

Yin Shi Yue-hua Chen Xiao-jun Yin and An-Qi Wangcontribute equally to this paper

Acknowledgments

This study is supported by the National Basic Research Pro-gram of China 973 programs (2009CB522900) The NaturalScience Foundation of China (no 30973784) and Shanghaitraditional Chinese Medicine talents construction project(no ZYSNXD-RC-LJRC)

References

[1] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disordersrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[2] D Keszthelyi F J Troost and A A Masclee ldquoIrritable bowelsyndrome methods mechanisms and pathophysiology Meth-ods to assess visceral hypersensitivity in irritable bowel syn-dromerdquo The American Journal of PhysiologymdashGastrointestinaland Liver Physiology vol 303 no 2 pp G141ndashG154 2012

[3] A P S Hungin P J Whorwell J Tack and F Mearin ldquoTheprevalence patterns and impact of irritable bowel syndrome aninternational survey of 40000 subjectsrdquoAlimentary Pharmacol-ogy andTherapeutics vol 17 no 5 pp 643ndash650 2003

[4] R M Lovell and A C Ford ldquoEffect of gender on prevalence ofirritable bowel syndrome in the community systematic reviewand meta-analysisrdquo American Journal of Gastroenterology vol107 no 7 pp 991ndash1000 2012

[5] D A Drossman M Camilleri E A Mayer and W E White-head ldquoAGA technical review on irritable bowel syndromerdquoGastroenterology vol 123 no 6 pp 2108ndash2131 2002

[6] M Camilleri ldquoManagement of the irritable bowel syndromerdquoGastroenterology vol 120 no 3 pp 652ndash668 2001

[7] L Chang A Lembo and S Sultan ldquoAmerican gastroenterolog-ical association institute technical review on the pharmacologi-calmanagement of irritable bowel syndromerdquoGastroenterologyvol 147 no 5 pp 1149ndash1172 2014

[8] R Spiller Q Aziz F Creed et al ldquoGuidelines on the irritablebowel syndrome mechanisms and practical managementrdquoGutvol 56 no 12 pp 1770ndash1798 2007

[9] D A Drossman ldquoThe functional gastrointestinal disorders andthe rome III processrdquoGastroenterology vol 130 no 5 pp 1377ndash1390 2006

[10] X-P Ma J Hong C-P An et al ldquoAcupuncture-moxibustionin treating irritable bowel syndrome how does it workrdquoWorldJournal of Gastroenterology vol 20 no 20 pp 6044ndash6054 2014

[11] G-Q Chao and S Zhang ldquoEffectiveness of acupuncture to treatirritable bowel syndrome a meta-analysisrdquo World Journal ofGastroenterology vol 20 no 7 pp 1871ndash1877 2014

[12] E Manheimer L S Wieland K Cheng et al ldquoAcupuncture forirritable bowel syndrome systematic review andmeta-analysisrdquoAmerican Journal of Gastroenterology vol 107 no 6 pp 835ndash847 2012

[13] X P Ma L-Y Tan Y Yang et al ldquoEffect of electro-acupunctureon substance P its receptor and corticotropin-releasing hor-mone in rats with irritable bowel syndromerdquo World Journal ofGastroenterology vol 15 no 41 pp 5211ndash5217 2009

[14] W CW Chu J C YWu D TW Yew et al ldquoDoes acupuncturetherapy alter activation of neural pathway for pain perceptionin irritable bowel syndrome a comparative study of trueand sham acupuncture using functional magnetic resonanceimagingrdquo Journal of Neurogastroenterology and Motility vol 18no 3 pp 305ndash316 2012

[15] H-G Wu H-R Liu Z-A Zhang et al ldquoElectro-acupuncturerelieves visceral sensitivity and decreases hypothalamiccorticotropin-releasing hormone levels in a rat model ofirritable bowel syndromerdquo Neuroscience Letters vol 465 no 3pp 235ndash237 2009

[16] J-W Park B-H Lee and H Lee ldquoMoxibustion in the manage-ment of irritable bowel syndrome systematic review and meta-analysisrdquo BMC Complementary and Alternative Medicine vol13 article 247 2013

[17] K F Schulz D G Altman D Moher and K F SchulzldquoStatement Updated Guidelines for Reporting Parallel GroupRandomised Trialsrdquo BMJ vol 340 p c332 2010

[18] G S Doig and F Simpson ldquoRandomization and allocationconcealment a practical guide for researchersrdquo Journal ofCritical Care vol 20 no 2 pp 187ndash191 2005

[19] C E Hewitt and D J Torgerson ldquoIs restricted randomisationnecessaryrdquo BritishMedical Journal vol 332 no 7556 pp 1506ndash1508 2006

[20] L-X Huang J-S Zhao Z-C Wu X-D Wu and Y-S TanldquoEditorial explanation on the state standard the name andlocation of acupoints (2006 edition)rdquo Zhongguo Zhen Jiu vol29 no 11 pp 924ndash926 2009

[21] M Bengtsson O Hammar T Mandl and B Ohlsson ldquoEvalu-ation of gastrointestinal symptoms in different patient groupsusing the visual analogue scale for irritable bowel syndrome(VAS-IBS)rdquo BMC Gastroenterology vol 11 article 122 2011

[22] M Bengtsson B Ohlsson and K Ulander ldquoDevelopment andpsychometric testing of the Visual Analogue Scale for IrritableBowel Syndrome (VAS-IBS)rdquo BMC Gastroenterology vol 7article 16 2007

[23] K Tillisch J S Labus B D Naliboff et al ldquoCharacterizationof the alternating bowel habit subtype in patients with irritablebowel syndromerdquo American Journal of Gastroenterology vol100 no 4 pp 896ndash904 2005

[24] D Luo S Liu X Xie and X Hou ldquoElectroacupuncture atacupoint ST-36 promotes contractility of distal colon via acholinergic pathway in conscious ratsrdquo Digestive Diseases andSciences vol 53 no 3 pp 689ndash693 2008

[25] E Noguchi ldquoAcupuncture regulates gut motility and secretionvia nerve reflexesrdquo Autonomic Neuroscience Basic and Clinicalvol 156 no 1-2 pp 15ndash18 2010

[26] Y-P Lin S-X Yi J Yan and X-R Chang ldquoEffect of acupunc-ture at Foot-Yangming Meridian on gastric mucosal bloodflow gastric motility and brain-gut peptiderdquo World Journal ofGastroenterology vol 13 no 15 pp 2229ndash2233 2007


[27] R Zhang L Lao K Ren and B M Berman ldquoMechanisms ofacupuncture-electroacupuncture on persistent painrdquoAnesthesi-ology vol 120 no 2 pp 482ndash503 2014

[28] J CWu E T Ziea L Lao et al ldquoEffect of electroacupuncture onvisceral hyperalgesia serotonin and fos expression in an animalmodel of irritable bowel syndromerdquo Journal of Neurogastroen-terology and Motility vol 16 no 3 pp 306ndash314 2010

[29] T Ji X Li L Lin et al ldquoAn alternative to current thera-pies of functional dyspepsia self-administrated transcutaneouselectroacupuncture improves dyspeptic symptomsrdquo Evidence-Based Complementary and Alternative Medicine vol 2014Article ID 832523 7 pages 2014

[30] S Takayama T Seki M Watanabe et al ldquoChanges of bloodflow volume in the superior mesenteric artery and brachialartery with abdominal thermal stimulationrdquo Evidence-BasedComplementary and Alternative Medicine vol 2011 Article ID214089 10 pages 2011

[31] X Li G Guo F Shen L Kong F Liang and G SunldquoMoxibustion activates macrophage autophagy and protectsexperimental mice against bacterial infectionrdquo Evidence-BasedComplementary and Alternative Medicine vol 2014 Article ID450623 6 pages 2014

[32] S Fukudo and M Kanazawa ldquoGene environment and brain-gut interactions in irritable bowel syndromerdquo Journal of Gas-troenterology and Hepatology vol 26 supplement 3 pp 110ndash1152011

[33] W Atkinson S Lockhart P J Whorwell B Keevil and L AHoughton ldquoAltered 5-hydroxytryptamine signaling in patientswith constipation- and diarrhea-predominant irritable bowelsyndromerdquo Gastroenterology vol 130 no 1 pp 34ndash43 2006

[34] C Stasi M Bellini G Bassotti C Blandizzi and S MilanildquoSerotonin receptors and their role in the pathophysiology andtherapy of irritable bowel syndromerdquoTechniques in Coloproctol-ogy vol 18 no 7 pp 613ndash621 2014

[35] M D Gershon ldquoSerotonin and its implication for the manage-ment of irritable bowel syndromerdquo Reviews in Gastroenterolog-ical Disorders vol 3 supplement 2 pp S25ndashS34 2003

[36] R C Spiller ldquoTargeting the 5-HT3receptor in the treatment of

irritable bowel syndromerdquo Current Opinion in Pharmacologyvol 11 no 1 pp 68ndash74 2011

[37] J K Anastasi D J McMahon and G H Kim ldquoSymptommanagement for irritable bowel syndrome a pilot randomizedcontrolled trial of acupuncturemoxibustionrdquo GastroenterologyNursing vol 32 no 4 pp 243ndash255 2009

[38] K M Cui W M Li X Gao K Chung J M Chungand G C Wu ldquoElectro-acupuncture relieves chronic visceralhyperalgesia in ratsrdquoNeuroscience Letters vol 376 no 1 pp 20ndash23 2005

[39] L Qi H-R Liu T Yi et al ldquoWarming moxibustion relieveschronic visceral hyperalgesia in rats relations to spinal dynor-phin and orphanin-Fq systemrdquo Evidence-Based Complementaryand Alternative Medicine vol 2013 Article ID 920675 10 pages2013

[40] J Tack M Camilleri L Chang et al ldquoSystematic reviewcardiovascular safety profile of 5-HT

4agonists developed for

gastrointestinal disordersrdquo Alimentary Pharmacology andTher-apeutics vol 35 no 7 pp 745ndash767 2012

[41] J M Hoffman K Tyler S J MacEachern et al ldquoActivation ofcolonic mucosal 5-HT

4receptors accelerates propulsive motil-

ity and inhibits visceral hypersensitivityrdquo Gastroenterology vol142 no 4 pp 844e4ndash854e4 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


its substantial therapeutic potency in managing variety offunctional disorders and pain syndromes

So far a large number of experimental studies have pro-vided robust evidence to support the efficiency of acupunc-turemoxibustion in IBS treatment and to illuminate themechanism underlying their multifunction and multitargeteffects [10] Meta-analysis on randomized sham-controlledtrials has verified the therapeutic efficiency of acupunc-ture in IBS management [11] and further suggested itssuperiority in achieving GI symptoms amelioration whencomparing to conventional pharmacological therapies [12]Electroacupuncture is a modern adaptation of traditionalChinese hand-manipulated acupuncture By adding a directelectrical current to needles the stimulation to the acupointscan be amplified and therefore improve its therapeutic effectElectroacupuncture was reported to have positive effecton modulating gastrointestinal motility secretion [13] painsensation [14] and brain-gut interaction [15] On the otherhand as another highly efficient Chinese Medicine therapybasing on the Meridians and AcupointsTheory moxibustionhas drawn much less attention than acupuncture despiteits equally robust effectiveness in clinical practice Existingclinical studies concerning moxibustion therapy on IBS werebarely persuasive due to their poor adherence to standardrandomized controlled trials (RCTs) criterion and conse-quently high risk of bias [16]

For this reason we designed this randomized parallel-controlled trial strictly following the CONSORT 2010 state-mentrsquos guideline [17] in order to provide credible clinical evi-dence to support the application of acupuncturemoxibustionin IBS treatment Also we expected that this study might ini-tially prove the distinguishing effects of electroacupunctureandmildmoxibustion on different symptoms of IBS and thuscan help clinicians to select the optimal treatment based onpatientsrsquo individual circumstances

2 Materials and Methods

21 Study Design This study was a parallel randomized con-trolled trial approved by the Chinese Clinical Trial RegisterCentre (registration number ChiCTR-TRC-11001349) Allthe participants were randomly allocated into EA group orMox group by a 1 1 ratio

211 Participants All participants were recruited from out-patients of the Department of Gastroenterology in Jin-hua Municipal Central Hospital between January 2012 andSeptember 2013

Eligibility criteria for participants were adults (aged 18ndash65 years) with symptoms consistent with IBS in accordancewith Rome III diagnostic criteria [9] who were willing toparticipate in the study and sign the informed consentPatients were to have had symptoms for at least three monthsand had diarrhea orand constipation occurring for at least 2daysweek Other physical diseases including cerebral vesselsdiseases liver or kidney diseases disorders of hematopoieticsystem or structural disease on the intestines were requiredto be absent or inactive Exclusion criterion also includesformal diagnosis of psychiatric disease receiving of any

medication aiming to treat IBS or thatmay induce IBS-relatedsymptomsmoxibustion or acupuncture treatment aiming forthe treatment of IBS within 2 weeks ahead of the treatmentsession and women during pregnancy or nursing

All the treatment interventions were performed byqualified and experienced acupuncture and moxibustionpractitioners from Department of Medical Clinic YueyangChinese and Western Medicine Integrated Hospital affiliatedto Shanghai University of Traditional ChineseMedicine whohave the Chinese Medicine practitioner license from theMinistry of Health of China

212 Randomization and Blinding Adopting the SNOSE(sequentially numbered opaque sealed envelopes) method[18] simple concealed randomization was carried out toeliminating possible selection bias [19] Participants wereallocated into electroacupuncture (EA) group or mild moxi-bustion (Mox) group on 1 1 bases

To avoid bias and intentional manipulation as far aspossible the initial symptom evaluation electroacupunctureor mild moxibustion intervention posttreatment symptomevaluation and data analysis were performed by differentpractitioners who were blinded to treatment arm assign-ments throughout the study Moreover the practitionerwho performed the electroacupuncture or mild moxibustiontreatment was not allowed to exchange any idea with theparticipants concerning their present symptoms or medicalhistory during the whole treatment session

This study has been approved by Ethics Committee ofYueyang Hospital of Integrated Traditional Chinese andWestern Medicine Shanghai University of Traditional Chi-nese Medicine of the research project (Approved number2010-08) All patients have been notified of their rights andsigned an informed consent

22 Interventions Each patient received a total of 24 EAMoxtreatment sessions once a day over four weeks suspendedon each Sunday Acupoints selection and EAMox treatmentwere performed according to Chinese Medicine theory Theacupoints ST-25 (Tianshu) and ST-37 (Shangjuxu) on bothsides of body were located following the national standard ofacupoint location GB-12346-90 [20]

For the EA group after 3 cm radius around the acu-points was sterilized with 75 ethanol disposable stainlesssteel needles (030 times 40mm Hwatuo Suzhou China) wereinserted into the skin to a depth of 20ndash25mm Twirling-rotating method was then applied to acquire a dull needlingsensation called ldquoDe Qirdquo After ldquoDe Qirdquo the electrical leadsof the HAN Acupoint Nerve Stimulator (HANS Model LH100A TENS Nanjing China) were connected to each needlewith stimulation frequency of 2Hz and intensity of 30mAfor 30min

The Mox group received mild moxibustion on the samefour acupoints for 30min Moxa rolls (18 times 200mm HwatuoSuzhou China) with one end ignited were hold vertically tothe skin 2-3 cm above the acupointsThe surface temperatureof the acupoints wasmaintained at 46∘Cplusmn 1∘Cby adapting thedistance between themoxa roll and the acupoint For every 3-4min the practitioners would flick the moxa ash into a trayin case the ash falls onto the skin and burns the participant








23 Outcome Measures




3R and 5-HT

4R


3R and 5-HT

4R in colon tissue





3R 1 50 and 5-



3R and 5-HT

4R


3 Results





Allocation

Analysis


Randomized (n = 82)

Excluded (n = 7)







(evection = 1)





Analysed (n = 38)



Analysed (n = 40)














Group Mox(119899 = 41)
















3R








4R in the











4R expressions
























Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)





deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of























23 Outcome Measures




3R and 5-HT

4R


3R and 5-HT

4R in colon tissue





3R 1 50 and 5-



3R and 5-HT

4R


3 Results





Allocation

Analysis


Randomized (n = 82)

Excluded (n = 7)







(evection = 1)





Analysed (n = 38)



Analysed (n = 40)














Group Mox(119899 = 41)
















3R








4R in the











4R expressions
























Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)





deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Allocation

Analysis


Randomized (n = 82)

Excluded (n = 7)







(evection = 1)





Analysed (n = 38)



Analysed (n = 40)














Group Mox(119899 = 41)
















3R








4R in the











4R expressions
























Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)





deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Group Mox(119899 = 41)
















3R








4R in the











4R expressions
























Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)





deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Baseline After

100

100

80

60

40

20

0

EAMox

(a)

Baseline After

100

110

100

90

80

70

60

50

EAMox

(b)

Baseline After

100

100

80

60

40

120

EAMox

(c)

Baseline After

100

100

80

60

40

20

0

EAMox

(d)

Baseline After

100

100

80

60

40

120

EAMox

(e)





deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















deviation



(a)


350

300

250

200

150

100

50

0

(b)


350

300

250

200

150

100

50

0


(c)


350

300

250

200

150

100

50

0


(d)









(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















(a)

MoxEANC

250

200

150

100

50

0

29 17


(b)

EA

250

200

150

100

50

0

29

29



(c)

Mox

250

200

150

100

50

0

17



(d)


3R expressions in







4 Discussion






(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















(a)

MoxEANC

100

80

60

40

20

0


(b)

EA

100

80

60

40

20

0



(c)

100

80

60

40

20

0

Mox



(d)


4R expressions in


























3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































3R expressions


3R in colon tissue




3R



















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















Acknowledgments


References





















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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