Cerebral Targeting of Acupuncture at Combined Acupoints in Treating Essential Hypertension: An ...

12 Pages·2016·1.59 MB·English

Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 5392954, 12 pages
http://dx.doi.org/10.1155/2016/5392954
Research Article
Cerebral Targeting of Acupuncture at
Combined Acupoints in Treating Essential Hypertension:
An Rs-fMRI Study and Curative Effect Evidence
YanjieWang,1,2YuZheng,1ShanshanQu,1JipingZhang,1ZhengZhong,1
JialingZhang,1HuanlinHuang,1MiaokengLi,1YiwenXu,1JunqiChen,3LeiWang,4
GenevieveZaraSteiner,5ChunzhiTang,6andYongHuang1
1SchoolofTraditionalChineseMedicine,SouthernMedicalUniversity,Guangzhou,GuangdongProvince510515,China
2WeinanVocationalandTechnicalCollege,Weinan,Shaanxi714026,China
3TheThirdAffiliatedHospitalofSouthernMedicalUniversity,Guangzhou,GuangdongProvince510630,China
4WeinanOrthopaedicsHospital,Weinan,Shaanxi714000,China
5TheNationalInstituteofComplementaryMedicine,SchoolofScienceandHealth,WesternSydneyUniversity,
Penrith,NSW2751,Australia
6ClinicalSchoolofAcupunctureandRehabilitation,GuangzhouUniversityofChineseMedicine,Guangzhou,
GuangdongProvince510405,China
CorrespondenceshouldbeaddressedtoChunzhiTang;[email protected];[email protected]
Received8August2016;Accepted12October2016
AcademicEditor:WarisQidwai
Copyright©2016YanjieWangetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Thestudyattemptedtoexplorethatthesynergisticeffectofacupointscombinationisnotasimplesuperpositionofsingleacupoint’s
effectbycomparingandanalyzingthechangesofbloodpressure(BP),SF-36,andbrainregionsafteracupuncturetreatment.47
patientswererandomlydividedintoLR3+KI3group,LR3group,andKI3group.SubjectsreceivedRs-fMRIscan,BPmeasurement,
and SF-36 questionnaires before and after treatment and short-term acupuncture treatment. After treatment, there were no
significantdifferencesinBPandSF-36among3groups,comparedtothecasebeforetreatment,SBPof3groupsdecreased,and
DBPsignificantlydecreasedwhilevitalityandmentalhealthsignificantlyincreasedinLR3+KI3group.Bothnumberandscopes
ofchangesofbrainregionsinLR3+KI3groupwerethelargest,whichmainlyincludedBAs3,4,8,19,21,24,32,44,and45.In
conclusion,acupunctureatLR3+KI3mayauxiliarilyreduceBPandimprovethevitalityandmentalhealthofpatients,andthe
changesofbrainregionswererelatedtosomatesthesia,movement,vision,audition,emotionandmood,language,memory,etc.
BAs4,9,10,24,31,32,and46maybethetargetingbrainareasofacupunctureinassistinghypotension.Itissuggestedthatacupoints
combinationofLR3+KI3maybegeneratesasynergisticeffect,anditisnotsimplesumofsingleacupointeffect.
1.Introduction previous research confirmed that the reasonable acupoints
combinationmostlyplayedasynergisticeffect[5,6].
Since1972,oneofthelonghistoryperiodsoftraditionalChi- Currently, the domestic and foreign research aims to
nesemedicinetherapies,acupuncturebegantobeappliedin explore the central mechanism of acupuncture therapeu-
theUnitedStatesandEurope[1].Nowadays,acupunctureis tic effects by using a noninvasive, visual, high-resolution,
oneofthemostpopulartreatmentsinalternativemedicine;it and reproducible functional magnetic resonance imaging
isincreasinglyvaluedbypeopleandwidelyusedintheclinic (fMRI) technology combined with acupuncture to observe
[2]. Relevant scholar generally recognizes that acupuncture thesignalchangesofthebrainareascausedbyacupuncture.
therapy is based on acupoints; two or more than two com- However, in most of the previous studies, subjects were
binedacupointsareusedfortreatingthedisease[3,4],and mostly healthy people, the observation of single acupoint’s
2 Evidence-BasedComplementaryandAlternativeMedicine
effects, comparing effects of single acupoint with nonacu- in patients [22]; however, another meta-analysis provided
point, effective acupoint with invalid acupoint, between evidence of acupuncture efficacy as an adjunctive therapy
acupoints, or real acupuncture with sham [7–12]. Recently, to western medicine for treating hypertension, while the
fMRI has gradually been applied to study the mechanism evidenceforacupuncturealoneinloweringBPisinsufficient
of acupuncture therapeutic effects based on some diseases; [23].Yinetal.[24]usedacupuncturecombinedwithbreath-
the study of effects of long-term acupuncture treatment in ingandeasy-walkingexercisestotreathypertension,finding
migrainepatientscomparedthedifferencesinbrainactivities thatsystolicbloodpressure(SBP)ofpatientswassignificantly
evocation by active acupoints and inactive acupoints [13]. decreasedafter8weeksoftreatment.Basedontheresearch
TostudytheinfluenceofacupunctureatWaiguan(TE5)on above, we speculate that acupuncture therapy may have
the functional connectivity of the central nervous system assistantantihypertensiveeffect.
of patients with ischemic stroke, Chen et al. [14] compared LR3 was one of the most frequently used acupoints for
the differences of regions of interest (ROI) between TE5 acupuncturetreatinghypertension[22,23,25].KI3wasalso
acupunctureandnonacupointacupuncture,aswellasverum usedfortreatinghypertension[23];besides,combinationof
acupunctureandshamacupuncture.Shietal.[15]researched LR3andKI3wasoftenusedtotreathypertensionclinically
an experimental acute low back pain model using fMRI to [25,26].Inrecentyears,researchofLR3andKI3acupuncture
exploretheneuralmechanismsofacupunctureanalgesiaby byfMRIisconstantlyongoing[9,27];ourteamalsocarried
meansofacupuncturestimulationandtactilestimulationat out Rs-fMRI research of acupuncture combination of LR3
BL40. These studies have revealed the possible mechanism andKI3[28,29],singleLR3[30],andsingleKI3[31],butall
of acupuncture therapeutic effects to some extent, but the subjects were healthy humans. Therefore, this study carried
clinical effect of acupuncture at two or more acupoints Rs-fMRI research of acupuncture combination of LR3 and
combinationandthecorrespondingchangeofbrainareasis KI3,singleLR3,andsingleKI3,withEHpatients.
orisnotthesumofthesingleacupointeffects,whichneeds In the current study, a randomized controlled trial,
furtherstudy. changes of BP and 36-item Short Form quality of life (SF-
Previous acupuncture research based on Block Design 36) between baseline and after acupuncture treatment were
fMRI[7,9,14]ignoredaftereffectofacupunctureandcould observed,andRs-fMRIwereadoptedtocomparethediffer-
notcompletelycopytheclinicalacupuncturetreatmentpro- enceinactivationofbrainregionsbyacupointcombination
cess.Atpresent,resting-statefunctionalmagneticresonance (LR3+KI3)andsingleacupoint(LR3orKI3)forEHpatients.
imaging (Rs-fMRI) technology has been gradually applied Furthermore,acorrelationanalysiswasperformedtoinvesti-
in the acupuncture research field. In order to avoid the gatethepossiblecorrelationamongclinicaleffects,activation
“stress”effectofacupunctureinthecourseofstudy,Rs-fMRI ofbrainregions,andacupointscombination.
scanwasconductedafterwithdrawingtheneedle,insteadof In summary, we hypothesize that the acupuncture at
during needle-retaining [8, 16, 17], which makes up for the LR3+KI3 for treating hypertension can produce synergistic
inadequaciesofBlock Designandcan actuallysimulatethe effect;comparedwithacupunctureatLR3orKI3,thesyner-
acupuncturetreatmentprocess. gisticeffectswillbemoreeffectivetoimprovethepatients’BP
In Rs-fMRI study, regional homogeneity (ReHo) is a andthechangeofbrainareasofacupointscombinationisnot
popular method of image data analysis. ReHo is a method asimplesuperpositionofsingleacupoint.
to assess resting-state brain activity by using the functional
coherenceofagivenvoxelwiththoseofitsnearestneighbors; 2.Methods
the advantage is that it can detect unknown hemodynamic
responses that the task driving method can not discover 2.1. Subjects. 150 EH patients in I grade or II grade were
[18].Therefore,Rs-fMRItechnologywasusedtocollectthe recruitedfromdifferentcommunityhospitalsinGuangzhou.
resting-state brain functional images of subjects before and ThisclinicaltrialwasregisteredinChinaandapprovedbythe
after acupuncture treatment, and the ReHo was used to ethical review committee (ChiECRCT-2012011) and clinical
analyzetheimagedatainthisstudy. trial registry in China (ChiCTR-TRC-12002427). Inclusion
Essential hypertension (EH) is an important risk factor criteriawereasfollows:(1)nolimitationofgenderandbeing
ofvariouscardiovascularandcerebrovasculardiseases,andit of35to65yearsoldandright-handed;(2)IstageorIIstage
hasbecomeoneoftheimportantchallengesofglobalpublic- and intermediate risk hypertension patients, who met the
health problem [19]. So far, antihypertensive medication is diagnosisandriskstratificationcriteriaoftheWorldHealth
stilldominantlyusedfortreatinghypertension;however,due Organization(WHO)/InternationalSocietyofHypertension
to the side effects or safety issues, such as drug resistance (ISH) 2003, and subjects who maintained their original
whichcouldaffecttherapeuticefficacy,thistherapyisfarfrom treatment (species and dose of antihypertensive medicine
satisfactory, so acupuncture therapy was selected as a com- did not change) during the study period and their BP was
monly used supplementary therapy for hypertension treat- controlled in the normal range but usually fluctuated (SBP
ment [20]. A systematic review of the current clinical evi- 120∼179mmHg and (or) DBP 80∼109mmHg). The drop-
dence of acupuncture treating hypertension showed that off criteria were as follows: (1) hypertensive crisis or other
therewassomeevidenceandsuggestedthattherewaspoten- emergencies;(2)realigningandexcludingsubjectswithmax
tial effectiveness [21]; a RCT of acupuncture affects the cir- head motion > 1.5mm on any axis and head rotation >
cadianrhythmofBPsuggestingthatacupuncturetreatment 1.5 degrees; (3) inability to complete this study because of
could be useful for improving the circadian rhythm of BP personal reasons. Adverse events were bleeding, hematoma,
Evidence-BasedComplementaryandAlternativeMedicine 3
Table1:Baselinecharacteristics(𝑋±SDor𝑋±SE).
Characteristic GroupA GroupB GroupC Statisticalvalue 𝑃
Gender(%)
Male 5(33.33) 1(7.10) 5(33.33) 𝜒2=3.492 0.174
Female 10(66.67) 13(92.90) 10(66.67)
Age(year) 54.47±7.13 56.29±7.74 56.73±5.12 𝜒2=1.275 0.529
Heredity(%)
Yes 11(73.3) 8(57.10) 7(46.70) 𝜒2=2.239 0.327
No 4(26.70) 6(42.90) 8(53.30)
Courseofdisease(month) 86.00±52.30 78.93±70.50 73.73±45.15 𝜒2=1.460 0.482
SBP(mmHg) 136.33±17.43 134.93±9.05 136.27±14.16 𝐹=0.045 0.956
DBP(mmHg) 89.47±8.43 86.29±7.35 81.33±9.16 𝐹=0.999 0.377
PF 88.33±2.05 85.71±3.39 92.67±1.68 𝜒2=3.349 0.187
RP 70.00±10.12 75.00±9.81 70.00±10.69 𝜒2=0.348 0.840
BP 77.47±3.66 79.07±3.97 82.20±4.37 𝜒2=1.198 0.549
GH 54.47±4.90 50.64±3.76 60.53±3.72 𝐹=1.414 0.255
SF-36 VT 70.33±4.77 68.21±4.96 81.33±2.91 𝐹=2.691 0.082
𝑋±SE SF 85.93±4.66 82.54±4.15 84.44±5.06 𝜒2=0.911 0.634
RE 84.44±7.88 73.81±9.36 68.89±10.01 𝜒2=1.582 0.453
MH 69.60±4.55 68.86±4.00 78.00±2.16 𝐹=1.897 0.163
fainting, serious pain, local infection, fluctuation of blood Acupuncture needles (0.3mm diameter, 40mm long,
pressure, and hypertension crisis. If any adverse events HwaTo, Medical Supplies Co., Ltd., Suzhou) were conven-
occurred during the study period, all the details were doc- tionally inserted. Once sensation of all needles occurred,
∘
umentedinthecasereportmanual. twisting (90–180 , 60–90times/min) and lifting-thrusting
According to random numbers table, all subjects were (0.3–0.5cm, 60–90times/min) of each needle were per-
randomly divided into LR3 and KI3 group (group A), LR3 formedfor1min,andthentheneedleswereretainedfor30
group (group B), and KI3 group (group C) and through minutes; during retaining needles period, the needles were
thesingle-blindmethod(Figure1).Demographics,including manipulated for 1 minute with an interval of 10 minutes.
gender, age, heredity, course of disease, SBP, DBP, and SF- Acupuncturetreatmentwascarriedoutonceaday,for5days,
36scale,didnotdifferamongthreegroups(𝑃 > 0.05)(see restedfor2daysandthenrepeatedforanother5days,10times
Table1). intotal.
2.1.1. Experimental Procedure. All subjects filled out SF-36 2.3. Blood Pressure Measurement. BP measurements were
scale at the beginning of the experiment, and then BP was taken before and after the treatment (posttreatment) with
measuredaftertakinga5minrest,andthentheyweregiven mercury sphygmomanometer (Jiangsu Yuyue Medical
abaselinefMRIscan.Next,participantsofthethreegroups EquipmentCo.,Ltd.).
receivedacupuncturetreatment.AllsubjectsfilledoutSF-36
scale again the next day after the end of acupuncture treat- 2.4. Rs-fMRI Scan. The fMRI scans were carried out in a
ment, and then BP was measured after taking a 5min rest, 3.0TeslaSignaHDxtMRIscanner(GECompany,Fairfield,
andthentheyweregiventhesecondfMRIscan(Figure2). America)atFirstAffiliatedHospitalofGuangzhouUniversity
ofChineseMedicine.Astandard8-channelphase-arrayhead
2.2. Acupuncture Intervention. In group A, acupuncture coilandrestrainingfoampadswereusedtominimizehead
stimulationwasperformedatLR3andKI3.IngroupBand motion.
group C, acupuncture stimulation was performed at LR3 Subjectswereconscious,placedinasupineposition,and
and KI3, respectively. According to the national standards askedtobreathecalmly.Earplugsandspecialearshieldwere
ofthelocationofacupoints(GB/T12346-2006),LR3locates used to diminish scanner noise, and eyeshades were used
on the dorsum of the foot, between the first and second to avoid visual stimulation. During the fMRI scan, subjects
metatarsal, in depression of basis metatarsalis junction in were instructed to move as little as possible and if they felt
front,ortouchingthearterialpulse.KI3locatesintheankle uncomfortable,theyshouldtellinvestigatorsloudlyandthe
area, in the depression between the medial malleolus and scanwouldbestopped.fMRIscanbeganaftersubjectsresting
achillestendon(Figure3). for15min.
4 Evidence-BasedComplementaryandAlternativeMedicine
Subjects screenedn=150
Excluded subjectsn=103
Met exclusion criterian=38
Not willing to participaten=33
Other reasonsn=32
Participantsn=47
Signedthe informed consent,
Random grouping
filled out general situation tables
Group An=16 Group Bn=15 Group Cn=16
(1) Before acupuncture treatment, SF-36 scale evaluation,
BP measurement, and fMRI can
(2) Acupuncture treatment
(3) After acupuncture treatment, SF-36 scale evaluation,
BP measurement, and fMRI scan
The moved range of 1case of voluntary 1case of time conflict
head was great, withdrawing
deleted 1 case
Group An=15 Group Bn=14 Group Cn=15
Figure1:Flowchartoftheparticipants.
② ③ ⑥
④ ⑦
Rest5min Rest5min
Rest-state Rest-state
① Me3asmurine BP T1WI fMRI BOLD Atcrueaptumnecntutre ⑤ Me3amsuirne BP T1WI fMRI BOLD
Fill out SF-36 3min 6min Fill out SF-36 3min 6min
Figure2:Flowchartoftheexperimentalprocedure.T1WI:T1-weightedimage;fMRI:functionalmagneticresonanceimaging;BOLD:blood-
oxygen-leveldependentcontrast;min:minutes.
MRIdata(resting-stateBOLDsequence)werecollected parameters:repetitiontime3,000ms/minimum,echo
15min before needling and the next day after acupuncture timeminimum,flipangle90∘,fieldofview240mm×
treatment: 240mm.
(1)Transverse T1-weighted image (T1WI) sequence:
2.5.StatisticalAnalysis
1min,51s,FastSpinEchosequence;OAxT1FLAIR,
repetition time 1,750ms/echo time 24ms, inversion
2.5.1.ImagePreprocessing. Thepreprocessingproceduresare
time 960ms, field of view 24cm × 24cm/Z, matrix
thesameasthoseinourpreviousstudy[31],whichinclude(1)
320 × 224/number of excitations = 1, thickness
convertingDICOMtoNIFTI,(2)slicetimingafterremoving
5.0mm/interval 1.0mm, 30 slices total, echo train
first 10 time points, (3) realigning and excluding subjects
length8,andbandwidth31.25. with max head motion > 1.5mm on any axis and head
(2)Resting-state fMRI BOLD data collection: gradi- rotation > 1.5 degrees, (4) Coregistering T1 to Fun, (5) seg-
ent echo-echo-planar imaging sequence scanning mentandaffixerregularizationaccordingtoEastAsian,(6)
conductedfor6mininaccordancewiththefollowing normalizing by using EPI templates, (7) removing linear
Evidence-BasedComplementaryandAlternativeMedicine 5
Table2:ChangesofaverageSBPandDBPofthreegroupsbetweenpretreatmentandposttreatment(𝑋±SD).
Time Items G(𝑛ro=up15A) G(𝑛ro=u1p4B) G(𝑛ro=up15C) Statisticalvalue 𝑃
SBP(mmHg) 136.33±17.43 134.93±9.05 136.27±14.16 𝜒2=0.091 0.955
BA
DBP(mmHg) 89.47±8.43 86.29±7.35 85.33±9.16 𝜒2=2.634 0.268
SBP(mmHg) 130.00±13.44 129.71±8.66 133.60±12.86 𝐹=0.489 0.617
AA
DBP(mmHg) 87.87±5.04 86.71±6.11 85.07±7.29 𝐹=0.769 0.470
BA:pretreatment;AA:posttreatment.
SBP, DBP, and SF-36, the paired t-test was used for intra-
group comparison of posttreatment and pretreatment; one-
wayANOVAorKruskal-WallisHwasusedforcomparison
among3groups.
3.Results
KI3
3.1.TheChangesofAverageSBPandDBPoftheThreeGroups.
LR3 Comparedtopretreatment,SBPandDBPofgroupAobvi-
ouslyreducedaftertreatment(𝑃=0.002,𝑃=0.038),SBPof
groupBobviouslyreducedaftertreatment(𝑃 = 0.006),and
SBPofgroupCobviouslyreducedaftertreatment(𝑃=0.002).
Comparisonofthreegroups’BPvaluesshowedthattherewas
nostatisticaldifferenceaftertreatment(seeTable2).
Figure3:ThelocationofLR3andKI3. 3.2.TheChangesofAverageSF-36ScaleoftheThreeGroups.
Comparedtobaseline,ingroupA,theSF-36surveyshowed
thatscoresofvitality(VT)(mean±SE,70.33±4.77versus
detrend,and(8)filtering(0.01Hz–0.1Hz).However,thedata 79.33±3.96,𝑃 = 0.011)andmentalhealth(MH)(mean±
waspreprocessedwithoutsmoothing. SE, 69.60 ± 4.55 versus 82.40 ± 4.94, 𝑃 = 0.018) improved
Afterpreprocessing,1casewasexcludedbecausethehead significantly after acupuncture treatment. Intercomparison
moving range was too large and 44 cases were included in of three groups showed that change in MH was significant
statisticalanalysis. difference(mean±SE,groupA:12.80±4.91,groupB:−2.57
±3.13,groupC:2.27±2.32,𝑃=0.010).
ReHoAnalysis.UsingtheREST1.8software,KCCmap(ReHo
maps)wasobtainedbycalculatingtheKendallconcordance 3.3.TheResultsofRs-fMRIScan
coefficient (KCC value) of the whole-brain voxel of each
case; the KCC maps by dividing their whole-brain KCC 3.3.1. Changes of Brain Regions of Posttreatment versus Pre-
equalizationobtainedstandardizedReHovalue[18]. treatment in Each Group. In group A, compared with pre-
treatment, the ReHo values of right inferior occipital gyrus
2.5.2.DataStatisticalAnalysis. UsingtheREST1.8software, (BA19),leftinferiorfrontalgyrusinopercularandtriangular
standardizedReHovaluesofeachgroup’stwotimepointsof part(BAs44,45),postcentralgyrus(BAs3,4),inferiorpari-
posttreatmentandpretreatmentwerecomparedbythepaired etal,excludingsupramarginalandangulargyrus(BA3),and
t-test, respectively. In order to avoid the impact of baseline left supramarginal gyrus were significantly increased, while
pretreatment, the comparisons of ReHo value among 3 right insula, superior temporal gyrus (BA21), precuneus,
groupsbeforetreatmentweremadeusingone-wayANOVA; medialsuperiorfrontalgyrus(BA8),anteriorcingulateand
if there was significant difference, ReHo values of 3 groups paracingulate gyrus (BAs 24, 32), and median cingulate
before treatment would be used as covariates, respectively, andparacingulategyrus(BA24)weresignificantlydecreased
thetwo-independent-samplet-testwouldbeusedtocompare (Table3,Figure4).
thedifferenceofpretreatmentandposttreatmentof3groups In group B, the ReHo values of right hippocampus
betweeneverytwogroups[13].Usingxjview8.0setstatistical (BA28), temporal pole in superior and inferior temporal
threshold probability was 0.05, AlphaSim correction was gyrus, precuneus, and BA31 were significantly increased,
applied(𝑃=0.05,theclustersize=228),thechangesofReHo while the ReHo values of right inferior parietal (excluding
between different groups before treatment and after treat- supramarginal and angular gyri) (BA40), supramarginal
mentwereobtained,andthebrainareaswithstatisticalsigni- gyrus,leftparacentrallobule,andmediancingulateandpara-
ficancewereshownintheformofimages.UsingSPSS20.0 cingulategyrus(BA24)weresignificantlydecreased(Table4,
for Windows statistical software for statistical analysis of Figure5).
6 Evidence-BasedComplementaryandAlternativeMedicine
+39mm +18mm +42mm
−3mm +12mm +6mm
Figure4:ThechangesofbrainregionsofgroupAaftertreatmentversusbeforetreatment.Note:theorangerepresentsthattheReHovalue
increased;thebluemeanstheReHovaluedecreases.
+24mm +15mm
−3mm +45mm −6mm
Figure5:ThechangesofbrainregionsofgroupBaftertreatmentversusbeforetreatment.
IngroupC,theReHovaluesofleftputamenandcaudate significantly increased, while right postcentral gyrus (BA3)
nucleusweresignificantlyincreased,whiletheReHovaluesof and paracentral lobule (BA5) were significantly decreased
rightpostcentralgyrusandleftfrontallobeweresignificantly (Table 6, Figure 7(a)). Compared to group C, group A
decreased(Table5,Figure6). showed that the ReHo values of right superior and middle
frontalgyrus(BAs9,46)andmedialsuperiorfrontalgyrus
3.3.2. The Comparison of Changes of Brain Regions among (BA10) were significantly increased (Table 6, Figure 7(b)).
3 Groups after Treatment. Compared to group B, group ComparedtoCgroup,BgroupshowedthattheReHovalues
A showed that the ReHo values of right precuneus (BA7) of right middle frontal gyrus in orbital part (BA46) were
and median cingulate and paracingulate gyrus (BA31) were significantly increased, while values of right superior and
Evidence-BasedComplementaryandAlternativeMedicine 7
Table3:ThechangesofbrainregionsofgroupAaftertreatmentversusbeforetreatment.
PeakMNIcoordinate
Numberofvoxels Hemi Brainareas BA T(peakintensity)
X Y Z
1248 R Inferioroccipitalgyrus 19 5.8152 39 −93 −15
313 L Inferiorfrontalgyrusintriangularand 44,45 3.6219 −9 60 18
opercularpart
Postcentralgyrus,inferiorparietal,
366 L excludingsupramarginalandangular 3,4 5.9703 −45 −27 42
gyri,supramarginalgyrus
344 R Insula,superiortemporalgyrus 21 −5.0278 45 −3 −15
551 R Precuneus — −6.7036 12 −60 42
Anteriorcingulateandparacingulate
851 R gyrus,mediancingulateand 8,24,32 −6.5526 6 12 27
paracingulategyrus,medialsuperior
frontalgyrus
Table4:ThechangesofbrainregionsofgroupBaftertreatmentversusbeforetreatment.
PeakMNIcoordinate
Numberofvoxels Hemi Brainareas BA T(peakintensity)
X Y Z
91 R Parahippocampalgyrus,temporalpole 28 4.5731 24 9 −33
(superiorandmiddletemporalgyrus)
87 R Precuneus 31 4.689 18 −48 36
102 L Mediancingulateandparacingulategyrus 24 −4.5841 −3 18 33
122 R Inferiorparietal,excludingsupramarginal 40 −4.1277 42 −39 45
andangulargyri,supramarginalgyrus
119 L Paracentrallobule — −3.717 −6 −24 48
Table5:ThechangesofbrainregionsofgroupCaftertreatmentversusbeforetreatment.
PeakMNIcoordinate
Numberofvoxels Hemi Brainareas BA T(peakintensity)
X Y Z
100 R Postcentralgyrus — 3.8341 30 −18 39
99 L Frontallobe — 4.3742 −30 −15 39
167 L Putamen — −4.1377 −21 6 12
Table6:Thecomparisonofchangesofbrainregionsamong3groupsaftertreatment.
PeakMNIcoordinate
Numberofvoxels Hemi Brainareas Brodmannarea T(peakintensity)
X Y Z
GroupAversusgroupB
739 R Precuneus,mediancingulateand 7,31 4.8486 12 −48 −36
paracingulategyrus
539 R Postcentralgyrus,paracentral 3,5 −5.545 15 −39 72
lobule
GroupAversusgroupC
Superiorandmiddlefrontal
120 R 9,46 3.5548 21 42 48
gyrus
98 R Medialsuperiorfrontalgyrus 10 3.6219 −9 60 18
GroupBversusgroupC
377 R Middlefrontalgyrusinorbital 46 5.5729 45 51 −9
part
496 R Superiorandmiddleoccipital 18,19 −4.3424 21 −78 18
gyrus
325 R Paracentrallobule 4 −4.0411 0 −30 69
8 Evidence-BasedComplementaryandAlternativeMedicine
+39mm −21mm acupoints combination can significantly improve VT and
MH of subjects; in addition, compared to groups B and C,
acupuncture LR3+KI3 can obviously improve MH of EH
patients. Both VT and MH are related to subjective feel-
ings;acupunctureatacupointscombinationmayhavesome
advantages in improving the emotional aspects. Adverse
mentalstimulationandnervousnessoflongtermhaveacer-
tainrelationshipwiththeoccurrenceofhypertension.There-
fore,thisstudyspeculatedthatantihypertensivemechanism
ofacupunctureLR3+KI3mayberelatedtothepsychological
and emotionalregulation. All participantsstill took antihy-
Figure6:ThechangesofbrainregionsofgroupCaftertreatment pertensivemedicationaccordingtotheoriginaltherapeutic
versusbeforetreatment. regimen; SBP of three groups was significantly reduced, so
thisstudypromptedthatacupuncturetherapymayhaveacer-
tainadjunctiveantihypertensiveeffect.GroupAwassuper-
middle occipital gyrus (BAs 18, 19) and paracentral lobule iortotheothertwogroupsindecreasingDBPandimproving
(BA4)weresignificantlydecreased(Table6,Figure7(c)). MH of hypertension patients; thus, the study infers that
No serious adverse events happened during the study. acupunctureatLR3+KI3mayproducesynergisticeffectinthe
ThreecasesingroupsAandBreportedhavingminorhem- treatmentofhypertension.
orrhage at the needling site. They were told to put pressure Rs-fMRI analysis found that there were changed brain
ontheneedlingareasfor3∼5minutesandrecoveredinfour areas in the three groups after acupuncture treatment. In
days. group A, the number of both clusters and changes of brain
areaswasthemost;therangeofchangesofbrainareaswas
4.Discussion alsothemostchangesofbrainareaswasalsothemostexten-
sive.
ThisisthefirstRs-fMRIstudythatfocusedonthesynergistic In group A, the changed brain areas relatively concen-
effectmechanismofacupointscombinationonEHtreating tratedinBAs3,4,8,19,21,24,32,44,and45;thefunctionof
by acupuncture. It demonstrated the similaritiesand differ- theabovementionedbrainareaswereasfollows:(1)somatic
ences in SF-36, SBP, and changes of brain regions between sensory cortex, relating to somatic sensory and perception,
acupuncture acupoints combination and single acupoint (2) primary motor cortex, controlling behavior and move-
treatment. ment,(3)premotorcortex(area)andfrontaleyefield,respon-
In this study, compared to pretreatment, SBP of three sibleformotionplanningandautonomiceyemovement,(4)
groupsposttreatmentwassignificantlyreduced,whichindi- secondaryvisualcortex,withthefunctionofdistinguishing
catedthatacupunctureatacupointscombination(LR3+KI3) object and face, (5) auditory organization cortex, involving
or a single acupoint (LR3 or KI3) may adjunctively reduce higherauditoryprocessingandlanguagereception,(6)par-
SBP.Inpreviousstudiesonacupuncturetreatmenthyperten- ticipating in the emotional system and involving the emo-
sion,YinandDu[20]foundthatpureacupuncturecannot tional judgment (especially pain) of somatesthesia, motion
onlyreducetheimmediateBPofpatientswithhypertension, planning,andmemoryprocessing,(7)Broca’sarea,involving
butthehypotensiveeffectremainsstable.However,Macklin languageproduction,executionofsemanticstask.Inanother
etal.[32]foundthatactiveacupunctureprovidednogreater study on acupuncture at LR3+KI3 of healthy people after
benefit than invasive sham acupuncture in reducing SBP withdrawing needles, cerebral blood flow changed in the
orDBP,andparticipantswereweanedoffantihypertensives brainareasrelatingtovision,emotionandmood,cognition,
during the study period. Flachskampf et al. [33] found that attention, phonological and semantic processing, memory,
in patients who still took antihypertensive drugs according andsoon[28];someresultsofacupunctureatLR3+KI3after
to the original treatment plan during the study period; treatmentinthisstudyweresimilartotheabovementioned
the BP was significantly lower in the acupuncture group study; it is suggested that the above brain areas relating to
compared with the sham group after 6 weeks of treatment; vision,emotionandmood,andlanguageandmemorymay
the change of BP in the subgroup of 35 patients without besomehowstimulatedbyLR3+KI3.
antihypertensivedrugsshowedadecreasingtrend.Yinetal. In group B, the changed brain areas were mostly BAs
[24] applied acupuncture therapy combined with breathing 24,28,31,38,and40;thefunctionsoftheabovebrainareas
andeasy-walkingexercisesfortreatinghypertension;SBPof wereasfollows:(1)theemotionalsystem,involvingtheemo-
patientswassignificantlylowerafter8-weektreatment,which tional judgment (especially pain) of somatesthesia, motion
issimilartotheresultsofourstudy.Astudyonacupuncture planning,andmemoryprocessing,(2)organizinghippocam-
treatmentEHindicatedthatshort-termsimpleacupuncture pus allowing the encoding and consolidation of memory,
didnotsignificantlydecreaseBP,butitmayimprovequality (3) relating to memory and emotion, and (4) secondary
oflifeforpatientsinrelationtobodypainandvitality[34]. somatosensory cortex, responding to somatic stimulation,
In this study, after acupuncture treatment, some aspects of and facilitating structural differentiation. In acupuncture at
the quality of EH patients’ life have certain influence by LR3 of healthy people after withdrawing needles, the brain
acupuncture at LR3+KI3, LR3, or KI3, and acupuncture at areasofchangingwererelatedtovision,somaticmovement,
Evidence-BasedComplementaryandAlternativeMedicine 9
−36mm −6mm
(a) ThecomparisonbetweengroupAandgroupB
+42mm −9mm
(b) ThecomparisonbetweengroupAandgroupC
−9mm +21mm −0mm
(c) ThecomparisonbetweengroupBandgroupC
Figure7:Thecomparisonofchangesofbrainregionsamong3groupsaftertreatment.
sensory,emotionandanalgesia,andsoon[30];someresults thisstudy;itissuggestedthattheabovebrainareasmaybe
of acupuncture at LR3 after treatment in this study were associatedwithstimulationofKI3.
similartotheabovestudy,buttherewasnosignificantchange Someofthechangesofbrainareasinthreegroupswere
in brain areas relating to vision, which was not consistent related to somatesthesia, movement, emotion, and mood,
withthepreviousstudies[35].Itissuggestedthatabovebrain andsomechangingbrainareaswerealsorelatedtomemory
areas relating to somatic movement, sensory, emotion, and processing in groups A and B; in addition, the changed
analgesiamaybestimulatedbyLR3. brain areas of group A were also associated with audition
The changed brain areas of group C were related to and language. It is suggested that the effect of acupuncture
somatesthesiaandperception,thinkingandplanning,indi- at LR3+KI3 may be based on the effect of single acupoint,
vidualneedsandemotion,andthecoordinationmovementof and activated brain areas of EH patients with acupuncture
muscle(maintainingacertainbodyposture).Inacupuncture at LR3+KI3 are not simple superposition of activated brain
at KI3 of healthy people after withdrawing needles, the areasofacupunctureasingleacupoint;namely,thatacupoints
changesofbrainareaswererelatedtoperception,movement, combination may generate a synergistic effect, which is
vision,audition,andspirit[31];thechangesofbrainareasof beyondthesimplesumofsingleacupoint’seffect.
acupunctureatKI3wererelatedtocognitivefunctioninpre- Thestudyofhypothalamus-seededrestingbrainnetwork
viousstudies[27],whilethebrainareasrelatingtovisionand underlying short-term acupuncture treatment in primary
auditiondidnotobviouslychange;thechangesofbrainareas hypertensionfoundthatincreasedpositivecorrelationswere
wereonlyrelatedtoperception,movement,andemotionin primarily located in the cerebellum, limbic system (insula,
10 Evidence-BasedComplementaryandAlternativeMedicine
parahippocampalgyrus,andcingulatecortex),bilateraltha- antihypertensive effect. The previous research found that
lamus,andfrontallobesaftertreatmentinacupuncturegroup acupuncture at LR3 could regulate the frontal lobe (such
[34].Inthepresentstudy,BPofthethreegroupsdecreased as BAs 4, 6, 9, 46, etc.) [38]. In both group A and group
after treatment, the changes of brain areas of three groups B compared with group C in this study, BAs 4, 9, and 46
were located in the frontal lobe, and the changes of brain changed; they were located in frontal lobe, and LR3 was
areasingroupsAandBwerelocatedinmediancingulateand needledintwogroups;thus,thisstudyfurtherconfirmedthat
paracingulate gyrus; besides, insula and anterior cingulate acupunctureLR3canmodulatethefrontallobefunction.
changed gyrus in group A, and parahippocampal gyrus Thereareseverallimitationsinthisstudy;forinstance,the
changedingroupB.Therefore,itissuggestedthattheabove samplesizeissmall,genderratioofmaleandfemaleisimbal-
brain areas may be associated with the targeting effect of anced,antihypertensivedrugsarestillbeingtakenduringthe
acupuncture decreasing BP; the brain areas associated with studyperiod,theobservationtimeisshort,thereisnocontrol
the antihypertensive effect of LR3+KI3 were not simple group (either waitlist or sham), and there are no long-term
superposition of the brain areas of targeting effect for anti- follow-up and evaluation of long-term curative effect; the
hypertensive effect of LR3 and KI3. Studies confirmed that aboveproblemswillbeimprovedinthefollowingresearch.
emotional changes have a certain impact on change of BP;
negative emotions have been linked to increases in blood 5.Conclusions
pressure,anxiety,depression,andangerleadingtoincreased
risk of hypertension [36], and the findings indicated an This study found that acupuncture at LR3+KI3 has the
associationbetweenhighpositiveemotionandlowerblood potentialtoauxiliarilydecreaseBPofEHpatients,strengthen
pressure among older Mexican Americans [37]. BAs 24, 31, the effect of antihypertensive medication, and improve the
and32arerelatedtoemotion;therefore,itisspeculatedthat vitality and mental health of patients. After treatment, the
theymaybethebrainareasoftargetingeffectforacupuncture number of changed brain areas were the most, and the
assistantantihypertensiveeffect. range was also the most extensive in acupoints combina-
Compared with group B, the changed brain areas in tion group; these brain areas were related to somatesthesia,
group A mainly included BAs 3, 5, 7, and 31, function of movement, vision, audition, emotion and mood, language,
which are as follows: (1) somatosensory projection cortex memory, and so forth. It is suggested that the effect of
and responsibility for somatosensory and perception, (2) acupunctureatLR3+KI3maybebasedontheeffectofsingle
somatosensoryassociationcortexandvision-motorcoordi- acupoint,andactivatedbrainareasofhypertensionpatients
nation,and(3)emotionprocessingandrecognition.Because with acupuncture at LR3+KI3 are not simple superposition
theemotionalchangehasacertaineffectonBPandBA31is of activated brain areas of acupuncture a single acupoint;
related to emotion processing and recognition, ReHo value namely, LR3+KI3 acupoints combination may generate a
of BA31 increased, its consistency of local neuronal activity synergisticeffect,anditisnotsimplesumofsingleacupoint
increased, and connection with the activity of peripheral effect.BAs4,9,10,24,31,32,and46maybethetargetingbrain
neuronsenhanced;onlySBPdecreasedingroupB;bothSBP areasofacupunctureinassistinghypotension;however,how
andDBPdecreasedingroupA,soitwasfurtherconfirmed theyaffectbloodpressurechangeisyettobefurtherstudied.
that BA31 may be one of the brain areas responding to the
CompetingInterests
targetingeffectdifferenceofacupunctureLR3+KI3andsingle
LR3regulatingBPchanges.
Theauthorsdeclaredthattheyhadnoconflictofinterests.
Compared with group C, the changed brain areas in
group A mainly included BAs 9, 10, and 46; they belong
Authors’Contributions
to the dorsal lateral prefrontal cortex; their function relates
to performance and cognition function, such as working ChunzhiTangobtainedfunding.YongHuangandChunzhi
memory and higher cognitive processing, central decision Tang participated in the study concept and design and
makingandperformance,andexecutivefunction.Compared manuscriptauthorization.YuZheng,YanjieWang,andJiping
with group C, the change brain areas in group B mainly Zhang recruited volunteers. Shanshan Qu and Junqi Chen
included BAs 4, 18, 19, and 46, function of which is as analyzed the data. Zheng Zhong and Huanlin Huang col-
follows: (1) primary motor cortex and controlling behavior lectedandorganizeddata.YanjieWangwrotethemanuscript.
motion, (2) vision association cortex and responsibility for YuZhengperformedtheacupuncture.JialingZhang,Yiwen
visual processing, and (3) executive function. In the study Xu,andLeiWangensuredtheintegrityofthedata.Genevieve
onfunctionalconnectivityofacupuncturetreatinghyperten- Zara Steiner analyzed the data and guided writing of the
sion, functional connectivity between bilateral frontal lobe manuscript.
and hypothalamuspositivelycorrelated, andthere isa fiber
connection between the prefrontal cortex and dorsomedial Acknowledgments
nucleus; dorsomedial nucleus is the location of complex
integrationeffectofviscusandidiosomaactivities.BAs4,9, This study was supported by the National Key Basic
10, and 46 are located in the frontal lobe, SBP of group B ResearchandDevelopmentProject(973Program),Grantno.
andgroupCdecreased,andbothSBPandDBPofgroupA 2012CB518504.Theauthorsareverygratefultothevolunteers
decreased;therefore,itisspeculatedthatBAs4,9,10,and46 andstafffromtheMRICenteroftheFirstAffiliatedHospital
maybethebrainareasresponsivetoacupuncture’sadjunctive of Guangzhou University of Chinese Medicine in China.