REVISTA
BRASILEIRA
DE
REUMATOLOGIA
ww w . r e u m a t o l o g i a . c o m . b r
Original
article
Acupuncture
in
fibromyalgia:
a
randomized,
controlled
study
addressing
the
immediate
pain
response
Rebecca
Saray
Marchesini
Stival
a,
Patrícia
Rechetello
Cavalheiro
a,
Camila
Stasiak
a,
Dayana
Talita
Galdino
a,
Bianca
Eliza
Hoekstra
a,
Marcelo
Derbli
Schafranski
b,c,∗ aFaculdadedeMedicinadaUniversidadeEstadualdePontaGrossa,PontaGrossa,PR,BrasilbUniversidadeFederaldoParaná,Curitiba,PR,Brasil
cUniversidadeEstadualdePontaGrossa,PontaGrossa,PR,Brasil
a
r
t
i
c
l
e
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f
o
Articlehistory:
Received23March2013 Accepted8June2014
Availableonline27October2014
Keywords: Acupuncture Fibromyalgia
VisualanaloguepainscaleChronic pain
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s
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c
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Objective:Toevaluatetheefficacyofacupunctureinthetreatmentoffibromyalgia, consider-ingtheimmediateresponseofthevisualanaloguepainscale(VAS)asitsprimaryoutcome. Methods:Randomized,controlled,double-blindstudyincluding36patientswith fibromyal-gia(ACR1990)selectedfromtheoutpatientrheumatologyclinic,SantaCasadeMisericórdia, PontaGrossa,PR.Twenty-onepatientsunderwentanacupuncturesession,underthe prin-ciplesofthetraditionalChinesemedicine,and15patientsunderwentaplaceboprocedure (shamacupuncture).Forpainassessment,thesubjectscompletedaVisualAnalogueScale (VAS)beforeandimmediatelyaftertheproposedprocedure.ThemeanchangeinVASwas comparedamonggroups.
Results:ThevariationbetweenthefinalandinitialVASvalueswas-4.36±3.23(P=0.0001)in thetreatmentgroupand-1.70±1.55inthecontrolgroup(P=0.06).Thedifferenceintermsof amplitudeofvariationofVAS(initial–finalVAS)amonggroupsfavoredtheactualprocedure (P=0.005).Theeffectsize(ES)forthetreatmentgroupwasd=1.7,whichisconsideredalarge effect.Althoughsmall,thestatisticalpowerofthesamplefortheseresultswasveryrelevant (94.8%).
Conclusion: Acupuncturehasproveneffectiveintheimmediatepainreductioninpatients withfibromyalgia,withaquitesignificanteffectsize.
©2014ElsevierEditoraLtda.Allrightsreserved.
DOIoforiginalarticle:http://dx.doi.org/10.1016/j.rbr.2014.06.001.
∗ Correspondingauthor.
E-mail:[email protected](M.D.Schafranski). http://dx.doi.org/10.1016/j.rbre.2014.06.002
SantaCasadeMisericórdiadePontaGrossa,PR.Vinteeumpacientesforamsubmetidos aumasessãodeacupuntura,nosmoldesdaMedicinaTradicionalChinesa,e15pacientes foramsubmetidosaumprocedimentoplacebo(acupunturasham).Paraavaliac¸ãodador,os indivíduospreencheramumaEscalaVisualAnalógica(VAS)anteseimediatamenteapóso procedimentoproposto.Asmédiasnavariac¸ãodaVASforamcomparadasentreosgrupos. Resultados:Avariac¸ãoentreovalordaEVAfinaledaEVAinicialfoide-4,36±3,23(P=0,0001) nogrupodetratamentoede-1,70±1,55nogrupodecontrole(P=0,06). Adiferenc¸ana amplitudedevariac¸ãodaEVA(EVAinicial–final)entreosgruposfavoreceuoprocedimento verdadeiro(P=0,005).Otamanhodeefeito(effectsize–ES)paraogrupodetratamentofoi ded=1,7,oqueéconsideradoumefeitogrande.Emboracomumaamostrareduzida,seu poderestatísticoparaessesresultadosfoibastanterelevante(94,8%).
Conclusão: Aacupunturamostrou sereficaznareduc¸ãoimediatada dor empacientes portadoresdefibromialgia,comumtamanhodeefeito(effectsize)bastantesignificativo.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Fibromyalgia is a non-inflammatory syndrome manifested
primarily on the musculoskeletal system by a chronic
widespreadpain,oftenassociatedwithothersymptomssuch as fatigue, sleep disturbance and mood disorders.1–3 The painusuallyexacerbatesafterphysicalactivityandthereare patientswhocomplainofitsintensificationwhenexposedto coldandhumidity.3
Theetiologyoffibromyalgiaremainsunknown,being con-sideredbysomeauthorsasasomatisationsyndrome.1But, mostlyfromthe1980son,thisconditioncametobe under-stoodasachronicpainsyndromeinwhichthesensitization ofthe centralnervous system(CNS) to painplaysa major role.Itsdiagnosticcriteriahavebeendefinedbythe Ameri-canCollegeofRheumatologyin1990,andin1992theWorld
Health Organization (WHO) recognized fibromyalgia as a
disease.4
The available treatments for this disease are only
par-tially effective and focus on the relief of symptoms;
and its cure, like other rheumatic diseases, constitutes
a still elusive task.5,6 Acupuncture has been applied
as a therapeutic modality in a wide variety of painful
conditions.7 Its neurobiological effects, that interfere on neurotransmitters related to pain and depression, qualify
this as a proper technique for the treatment of chronic
pain.7,8
Inthisstudy,wesoughttoevaluatetheefficacyof acupunc-ture in treating fibromyalgia, considering the immediate responseofthevisualanaloguescaleofpainastheprimary outcome.
Material
and
methods
Patientsandcontrols
Thirty-six patients with fibromyalgia diagnosed according to the 1990 American College of Rheumatology classifica-tion criteria seen at the outpatient rheumatology clinicat the Hospital Santa Casa de Misericórdia, Ponta Grossa (Uni-versity Hospital, UEPG) were selected. Volunteers selected for the study were randomly distributed into two groups. Patientswithcontraindicationtoacupuncture,forinstance, individualswithneedlephobia,bleedingdiathesis,pregnant orlactatingwomen,wereexcluded.
Thesamplesizecalculationwasperformedbyestimating aCohen’sdcoefficient=1.2(effectsize)foran␣-errorof5% andasamplepowerof80%,andweinferredthattherequired samplesizewasasleast12patientsineachgroup.
The randomization followed a computer generated
table of random numbers by Research Randomizer (www.
randomizer.org). The study was approved by the Universi-dade Estadual de Ponta Grossa (UEPG) Ethics Committee on HumanResearch(COEP)andallindividualsinvolvedsigned aninformedconsentform.
Table1showsthebaselinecharacteristicsoftheselected patients. There was no statistically significant difference betweenthetwogroups.
Intervention
PC6 PC6
IG4
BP6
BP6
IG4
C7 C7
E36
F2 F2
E36
Figure1–Acupuncturepoints.Pericardium6(PC6),Heart7(C7),Spleen6(BP6),LargeIntestine4(IG4),Liver2(F2),Stomach 36(E36)pointswereusedbilaterally.
theirinterventiongroup.Thechosensitestothetreatment were the points: the large intestine4, stomach36, liver2, spleen6,pericardium6andheart7bilaterally,accordingto whatis recommended byTraditional ChineseMedicine.9,10
Fig. 1 shows, schematically, the acupuncture points
employed.
Agroupof21patientsunderwentacupuncturewith nee-dlesof0.20×40mminserted perpendicularly atthepoints describedabove,i.e.,preciselyrespectingtheanatomical loca-tion described inTraditional Chinese Medicine.Agroup of
Table1–Baselinecharacteristicsofpatients.
ShamAcupuncture Acupuncture
n=15 n=21 P
Age 49.2±11.8 52.0±7.57 0.38a
Gender
Male 1(6.6%) 4(19.5%) 0.28b
Female 14(93.3%) 17(80.4%)
VAS,initial 5.72±2.50 7.27±2.66 0.08a
Durationofdisease 9.07±6 7.3±5.98 0.5c
Dataarepresentedasmean±standarddeviation,exceptwhere indicatedbyc,thatforreasonsofnon-parametricdistribution,the
interquartilerange(IQR,comparisonperformedbyMann-Whitney test)wasused.
a Student’sttest. b Student’sexacttest.
15patientsreceivedshamacupuncture,whichcomprisesthe useoftheneedlesasplacebo.Inthisprocedure,needlesof 0.18×8mm were used to stimulate points on the surface 15mmtotheleftofthetruepoints.11,12
Thesameacupuncturist,notaphysician,butatthetime withtheappropriatequalificationtoperformthis therapeu-ticmodality,ledtheproceedings.Bothconversationsbetween theacupuncturistandthepatientasanycontactbeyondwhat was consideredstrictly necessaryforthe acupuncture pro-cedure, were restricted. The session ofacupuncture lasted 20minutes.
Outcomeassessment
Immediatelybeforeandaftertheintervention,patients com-pletedavisualanalogscale(VAS)forpain,whichconsistsof arulerwithascaleof0to10cm,withthenumberzero rep-resentingnopain,andthenumber10beingtheworstpain everexperiencedbythesubject.Withintheproposed proto-col(adouble-blindstudy),theprofessionalswhocollectedthe responsesofVAS forpainwereunawareofthe randomiza-tionstatusofeachindividual.Onlytheacupuncturistknew theinterventiongroups.
Statisticalanalysis
usingtheStudent’sttest(unpairedforbasalcharacteristics andmatchedfortheresults)andnon-parametricdistributions
were tested using the Mann-Whitney test. For comparison
ofcategoricalvariables,thetwo-tailedFisherexacttestwas applied.Data arepresentedasmean± standarddeviation, except whereindicated (mean±interquartile range – IQR). Pvalues <0.05wereconsideredstatisticallysignificant.The effectsizeisdemonstratedbyCohen’sdcoefficient,that con-siders0.2asasmalleffect;0.5asamediumeffect;and0.8 asalargeeffect.Toestimatetheobservedstatisticalpower ofthesample, it wasconsidered asappropriatean␣-error (typeI)of5%andan-error(typeII)of20%.Allanalyzeswere performed using MedCalc software,version 12.4.0 (Ostend, Belgium).
Results
Both groups showed improvement in the outcome
analy-sisofVAS aftertheproposed intervention (Table 2). Inthe treatmentgroup,therewasachangeof-4.36±3.23between initialand finalVAS values, whichwas statistically signifi-cant(P=0.0001).Intheshamgroup,althoughaconsiderable
change was observed in VAS (-1.70±1.55), this
differ-ence did notreach the threshold ofstatistical significance (P=0.06).
However, in relation to the effect size measured by
the Cohen’s d coefficient, the acupuncture procedure has beenshowneffectiveinbothgroups:theshamintervention resultedin an effectconsidered medium (d=0.69) and the acupunctureresultedinalargeeffect(d=1.7).
Andfinally,withrespecttotheamplitudeofVASvariation (initial–finalVAS),thedifferenceamonggroupsfavoredthe actualprocedurewithstatisticalsignificance(P=0.005),with aCohen’sdcoefficient=1.05(largeeffect).
Despite the relatively small sample size, estimating an ␣-errorof5%, theobserved statisticalpower demonstrated bythe samplewas 94.8%,with aconsequent -error(type
II) of only 5.2%, which confirms the robustness of our
findings.
Discussion
Thepresentstudyaimedtoevaluatetheimmediateresponse ofVASforpaininfibromyalgiapatients,diagnosedaccording toACRcriteria(1990),afterasinglesessionofacupuncture, comparingtocontrolssubjectedtoashamprocedureaftera randomizationprocess.
sameneurotome.7,14Somestudieshaveshownthat acupunc-turestimulatesthe releaseofendorphinsand enkephalins,
which leads to a modulating pain response, resulting in
analgesia.7,15 Other studies have shown that acupuncture may blockthe painafferentsbytwomechanisms: the first byinhibitingtheactivityofpaintransmissionneuronsata medullarylevel;thesecondbyinhibitingnociceptiveafferent stimulithroughtheactivationofsegmentaland suprasegmen-tal pain suppressorsystems.6,7 Theconceptofsensitive or tenderpoints,althoughtodaycontroversialinthediagnosis offibromyalgia,hasacloserelationshipwiththeconceptof acupuncturepoints.Thestimulationofthesepointswith nee-dlescanpromotepaincontrol.16Theeffectsofacupuncture on brainactivity havebeen demonstratedthroughimaging studies,whichshowedthat,aftertheacupunctureneedling, there is an intensification of cerebral blood flow.6,7 Thus, many patientswith chronicpainturn totreatment bythis technique.7,10,17
The studies on acupuncture specifically for treating
fibromyalgiahaveshownquitecontroversialresults.
Assefiet al.,11 inarandomized,controlled,double-blind study,evaluatedtheefficacyofacupunctureinrelievingpain in 100 fibromyalgia patients. These subjects were divided intofourgroupsaccordingtotheintervention:acupuncture programthatwasspecificallydesignedtotreatfibromyalgia, accordingtotheprinciplesofTraditionalChineseMedicine; acupunctureuseforotherconditions,exceptforfibromyalgia; useofplaceboneedlesindifferentpointsofEnergy Meridi-ans;andstimulationoftheskinwithatoothpick,simulating
needle insertion. The authors concluded that
acupunc-ture treatment isnotsuperior to shamtreatment forpain relief.
Sanchez et al.18 performed a systematic review on
the effectiveness of acupuncture in treating fibromyalgia.
After a critical analysis of studies indexed at PubMed,
the Cochrane Library, EMBASE, CINAHL and at Pascal
Biomed, six studies were selected from 59 found. The
analysis of these six studies led to the conclusion that
there is no evidence of benefit of acupuncture compared
to sham acupuncture in the treatment of
fibromyal-gia.
On the other hand, ina randomized single-blind study Deluze etal.19 evaluatedthe efficacyofelectroacupuncture in patients with fibromyalgia. In a group of 70 patients,
36 received electroacupuncture at pointsrecommended by
the Traditional Chinese Medicine and 34 received sham
acupuncture(theneedlingwasmadeinpoints20mmaway
from the true points and with reduced electrical stimula-tion).Intheelectroacupuncturegrouptherewasasignificant
improvement of symptoms. In five of the eight
electroacupuncturewasmoresignificantthaninthecontrol group.
ItohandKitakoji,20inapreliminaryrandomizedcontrolled study,evaluatedtheimpactofacupunctureonpainand qual-ityoflifein16patientswithfibromyalgia.Thepatientswere dividedintotwogroupsofeightpatientswhounderwent10 weeklyacupuncturesessions.Thecontrolgroupreceivedthe actualtherapyonlyafterthefirstfiveweeks.Aclear improve-ment inbothFIQ (Fibromyalgia Impact Questionnaire)and VASinthecontrolgroupwhichwasperceivedonlyafterthe applicationoftheactualproceduresuggestedthat acupunc-turetreatmentiseffectiveinrelievingpaininpatientswith fibromyalgia.
Martinetal.10conductedarandomized,partiallyblinded,
controlled study in which 50 patients with fibromyalgia
were subjected to six treatment sessions in two groups:
actual vs. sham (stimulation of the skin by the needle,
butwithoutpenetratingtheskin)acupuncture.Theauthors concludedthatacupunctureiseffectiveintreatingthe symp-tomsoffibromyalgia, especiallywithregardtoanxietyand fatigue.
Thepresentstudy,carriedoutbyadouble-blind random-izeddesign,favorstheacupunctureintermsofanimmediate painimprovementin patientswithfibromyalgia. This con-clusionwas obtainedbyasignificantlyrobustdifference in VASvariation,observedinpatientsundergoingtheactual pro-cedure. Itis noteworthy to observe that both intervention groupsshowedasignificantandimmediateimprovementin pain,withexpressiveCohen’s dcoefficients,representing a mediumeffectsizeforshamacupunctureandalargeeffect size forthe actual acupuncture. This fact is in agreement withPariente et al.,21 who examined thepain response to acupuncturevs.ashamprocedureusingfunctionalMRI,and demonstratedthatbothproceduresactivatecorticalregions relatedtoanalgesia,suchasthedorsolateralprefrontal cor-texandtheanteriorsingularcortex,buttheactualprocedure results in an insular activation that is not seen after the simulation.21
Despite the reduced sample size, the statistical power observedwashigh,withanalmostexpressionless-error,in faceoftheimportantdifferenceinresponseamongthegroups evaluated.
Fromthefindingsofthisstudy,itappearsthat acupunc-tureperformedinaccordanceoftraditionalChineseMedicine
has an important effect on the immediate reduction of
paininpatientswithfibromyalgia,comparedtotheeffects
of sham acupuncture. More studies with different
proto-cols are needed to confirm this hypothesis, with a larger numberofindividuals andwithalonger follow-up,mainly to evaluate more accurately the duration of the analgesic effect.
Funding
The researchersPatrícia Rechetello Cavalheiro and Camila Stasiakreceivedan educationalgrantfrom CNPq(PIBIC) to implementtheproject.TheresearcherBiancaElizaHoekstra receivedasupportgrantfromAraucariaFoundation(BIC)for thesamepurpose.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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