Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and Substance P Levels

14 Pages·2017·0.42 MB·English

PainMedicine2018;19:615–628
doi:10.1093/pm/pnx263
INTEGRATIVE MEDICINE SECTION
Original Research Article
Effects of Acupuncture Treatment on
Fibromyalgia Symptoms, Serotonin, and
D
Substance P Levels: A Randomized Sham and ow
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Placebo-Controlled Clinical Trial d
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Saliha Karatay,MD,* Sibel CaglarOkur, MD,†Hulya serotonin andsubstanceP (SP)aswellason clini- ://a
Uzkeser,MD,‡ KadirYildirim,MD,‡ andFatihAkcay, calparametersinpatientswithfibromyalgia(FM). ca
d
MD§ e
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Methods. This is a randomized controlled clinical ic.o
*HealthScienceFaculty,DepartmentofPhysiotherapy trial.Seventy-fivewomenwithFMwererandomized up
and Rehabilitation,GaziUniversity, Ankara,Turkey; into one of three kinds of acupuncture treatment: .co
m
†DepartmentofPhysicalMedicineand Rehabilitation, real acupuncture group (AcG), sham acupuncture /p
MinistryofHealth, IstanbulTraining andResearch group (ShG), and simulated acupuncture group ain
Hospital, Istanbul,Turkey;‡DepartmentofPhysical (SiG). Treatmentswere applied semiweekly for four me
Medicineand Rehabilitation,AtaturkUniversity, weeks. The serum levels of serotonin and SP were dic
BEMrieozdcuhricueamml,FisTaturcyru,kletAyyt,aEturzrkurUumniv,eTrusritkye,yM;§eDdeicpaalrFtmaceunlttyo,f ePsFvciabaatrilleouenmat(tsyVeadAwlSgeib)ar,eeftohcImrelienpniacaucanmtldlybQeaaursfetsoeserftsiosttenehndnedabeierryeigpvhio(stFiunIQsatsel),sa(snNBiaoTelnPocs)gk,. ine/article-a
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Correspondenceto:SalihaKaratay, MD,Department DepressionInventory(BDI),andNottinghamHealth stra
oSfcPiehnycseio,tGhearzaipUynaivnedrsRitye,hAabnkiliataratio0n6,5S0c0h,oToulrkoefyH.ealth Panrodfiolene(NaHnPd) tahtrebeasmeloinneth,safateftrerthceomlapsltettrioenatmofenatll, ct/19
Tel:[phone];Fax:[phone]; treatments. /3/6
1
E-mail: [email protected]. Results. Serum serotoninvalues increased signifi- 5/46
8
Funding sources:The studyhadnofunding source. cantly after treatment in AcG and ShG (P<0.001 9
1
All authorssupportedthe studybythemselves. and P<0.01, respectively). The increase in the 81
AcG was also different from both of the other by
Conflicts ofinterest:Wedon’t haveconflictsofinterest groups(P<0.01).WhileSPlevelsdecreasedinthe gu
or commercialrelationships,includinggrants,hono- e
AcG, they increased in the SiG (P50.001). In the s
raria,speaker’s lists,significantownership,and/or AcG, significant improvements were found in al- t on
support frompharmaceuticalorothercompanies most all clinical outcomes after treatment. These 27
suchas manufacturesofequipment,diagnostic or usually continued for three months. In the ShG, M
a
otherlaboratories whoseproducts aredirectlyorindi- there were also significant changes on the NTP, rc
h
rectly involvedoraffected bythe article. VAS, FIQ, and BDI scores after treatment. 2
0
Improvements on the NTP and FIQ scores lasted 19
Disclosure: Financialdisclosure statementshavebeen
for three months. In the SiG, significant improve-
obtained,and noconflictsofinteresthavebeen ments were found only in the NTP, VAS, and BDI
reportedby theauthorsor byany individualsin con- scoresaftertreatment.
trol ofthe contentofthisarticle.
Conclusions. Acupuncture, rather than sham or
placebo acupuncture, may lead to long-term
Abstract improvementsonclinicaloutcomesandpainneuro-
mediator values. Changes in serum serotonin and
Objective. Theaimofthisstudywastoevaluatethe SP levels may be a valuable explanation for acu-
effectsofacupuncturetreatmentonserumlevelsof puncturemechanismsinFMtreatment.
VC 2017AmericanAcademyofPainMedicine.Allrightsreserved.Forpermissions,pleasee-mail:[email protected] 615
Karatay etal.
Key Words. Fibromyalgia; Treatment;Acupuncture; Many studies have shown the benefits of acupuncture
Serotonin;SubstanceP;Pain in the symptoms of FM [15,16]. However, the majority
of these reports focused on pain reduction. Patients
with FM have not only pain, but other symptoms as
Introduction
well, such as morning stiffness, anxiety, depression,
lower quality of life, fatique, and sleep abnormalities.
Fibromyalgia (FM) is a kind of nonarticular soft tissue
Although important improvements were reported with
rheumatism characterized by chronic and widespread
acupuncture treatment in patients with FM, the effect
musculoskeletal pain, short-term stiffness, subjective
mechanism of acupuncture is unknown. Acupuncture
swelling feeling, fatique, and sleep disturbances [1].
may regulate to one or more altered etiopathogenetic D
Prevalence of FM is about 2–4% of the general popula- o
mechanismsinthetreatment ofFM. w
tion, and 80–90% of patients are women [2]. Although n
FM is the second most common painful disorder, the loa
Acupuncture treatment has both local effects, such as d
etiopathogenesis is certainly unclear. At the beginning, e
local microinflammation due to needles, an increase in d
microtraumas, local inflammations, and aberrant micro- local blood flow, and analgesia, and general effects, fro
circulation on muscles were blamed for mechanisms of m
FM [3]. Nowadays, however, etiopathogenesis focuses such as somato-autonomic reflex and neurotransmitters h
in the brain [20]. Several studies have shown that the ttp
on changing pain mechanisms and stress management. s
SeveralhypothesesaresuggestedregardingFM,includ- stimulation of acupoints can affect the concentrations of ://a
ing altered hypothalamus-pituitary-adrenal (HPA) axis, various mediators, such as endorphin, serotonin, SP, ca
d
changing peripheral nociception, and central sensitiza- and enkephalin in the brain and local tissues [21–23]. em
tion[4]. Although it is well known that abnormalities in pain reg- ic
.o
ulation play an important role in FM clinical symptoms, u
p
One major hypothesis in the etiology of FM is serotoner- there are few studies investigating the relationship be- .c
o
gic dysfunction. Serotonin has an important role in pain, tween changes in pain-modulating substances and in m
emotion, mood, cognition, and various motor functions clinical symptoms with acupuncture treatment in /pa
[5]. Several reports determined low serotonin values in patients with FM [24]. Also, acupuncture treatment can inm
patients with FM [6,7]. Also, a strong correlation was change SP and serotonin concentrations in several acu- ed
observed between lower levels of serotonin and pain or points and in patients with a variety of diseases; how- icin
hyperalgesia [8]. The implication was that low levels of ever, there are no adequate clinical trials regarding this e/a
serotonin may be related to other abnormal factors, issueinFM[25–27]. rtic
such as altered HPA axis and sympathetic hyperactivity le
-a
in FM [9]. Another important mediator in pain transmis- If acupuncture is effective in pain reduction of patients b
s
sionandsensationis substanceP(SP).Itworks innoci- with FM, changes in serotonin and SP levels may ex- tra
ception, hyperalgesia, allodynia, and neurogenic plain how acupuncture works in the treatment of FM. ct/1
inflammation [10,11]. It was reported that SP levels in- 9
However, to the best of our knowledge, the effects of /3
crease in the cerebrospinal fluid (CSF) of FM patients acupuncture treatment on serum SP and serotonin lev- /6
1
[p1a2in].tAhlrseos,hsoeldrostoinniFnMa.nd SP abnormalities may influence edlosmhizaevde cnoonttrboelleend pcrlienvicioaulstlyriailnv(ReCstTig)atinedpawtiitehntas wrainth- 5/468
9
FM. Therefore, we aimed to investigate if acupuncture 1
As FM is a chronic painful disease and the etiopatho- 8
genesis remains unclear, there is no gold standard therapy can change serum SP and serotonin levels as 1 b
treatment for FM patients. Several pharmacologic and wellasclinicalparameters. y g
u
nonpharmacologic approaches, such as exercise, cog- es
nitive behavior therapies, and patient education are Methods t o
n
recommended in FM treatment [13,14]. The pharmaco- 2
This study was conducted at the Physical Medicine and 7
logical treatments include mainly antidepressants, anal- M
gisniedssueicffsiec,fifeeancnttdsremsdpuuoesncslteoertepolhaasxryammntapsc.tooHmloogswicoeatvlheedrr,rutlihgmasinterdpesabtinreic,ntaenfititds, RsAtteuahdtauybrkiwlitUaastnioivaneprpsDirtoyev.peaAdrltlmbpeyanrtttihceiopfaloncAtsatalwteuetrhkreicsUinnfcoiovremmrsemidtiytt.aebeTohuoetf arch 201
the study protocol but not about the kinds of groups. 9
use [15]. Patients who suffer from chronic FM seek
alternative therapy because of conventional medicine Their written informed consents were obtained accord-
failure [16]. It was reported that more than 90% of FM ingtotheDeclaration ofHelsinki.
sufferers experiencedatleast onekind ofCAM[17].
Seventy-five female patients with FM (age 20–50years)
The American Pain Society FM guidelines report moder- were enrolled in this study. The number of tender points
ate evidence for acupuncture therapy in the treatment (NTP) was an important clinical assessment parameter
of FM according to clinical trials [18]. Also, the NIH ac- in the study. Therefore, the 1990 American College of
cepted as a consensus statement that acupuncture Rheumatology (ACR) FM criteria, which included NTP,
therapy may be a useful adjunct or alternative treatment were used for FM diagnosis instead of the 2010 ACR
forFM[19]. criteria[28,29].
616
Acupuncturein Fibromyalgia
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Figure1 Needlingpointson anteriorview. Figure2 Needling pointsonposterior view. e
/a
rtic
People who had taken nonsteroidal anti-inflammatory recognized as acupoints or in meridians. These sham le
drugs, selective serotonin reuptake inhibitors, tricyclic points were defined by using an acupuncture point -ab
s
antidepressant or any antidepressant drugs in the previ- search dedector approximately 1–2cm from AcG’s tra
oatuhses1i5sdoarysp,aainndfulwhmoedsimcaolkecdo,nwdihtioonhsadotahebrletehdainngFdMi- aaccuuppooiinnttss. aTchceorpdoiningtst,owthhiechdheadveectolorw, ewresreignuaslsedthaans ct/19
were not included. Also, patients who had prior experi- shampoints. /3/6
1
ence with any acupuncture therapy were excluded from 5
the study. Randomization was assured through a simple In the SiG, 18 identical real acupoints with the AcG /46
randomization method, using closed envelopes with were used. Noninsertive simulated acupuncture was 89
1
numbers inside. Seventy-five female patients were ran- performed on this group. First, a small circular adhesive 81
domly assigned to three groups: the acupuncture group bandage was applied on an acupoint. Then, a short b
y
(AcG), the sham acupuncture group (ShG), and the sim- needle (0.25(cid:2)15 mm) was inserted into the bandage g
u
ulated acupuncture group (SiG). In the AcG, acupunc- but not into the skin. In this group, short needles were es
ture treatment was performed on 18 acupoints preferred, so that patients assumed that the needles t o
n
designed to treat FM with 0.25(cid:2)25 mm stainless steel had been inserted into the skin. While the needles were 2
7
needles. These standardized acupoints were Du-14 (Da inserted into acupoints and sham points, they were not M
Zhui), Si-15 (Jian Zhong Shu), Li-4 (He Gu), Li-11 (Qu inserted into the points of the SiG. Also, small circular arc
Chi), H-7 (Shen Men), P-6 (Nei Guan), Ren-6 (Qihai), adhesive bandages were used in all groups to ensure h 2
Liv-3 (Tai Chong), St-36 (Zu San Li), and Sp-6 (San Yin thesameappearanceamongpatients. 01
9
Jiao). They were used bilaterally, except Du-14 and
Ren-6points(Figures1and2). Blinding
Two different control groups were used in this study. The treatments in all three groups were performed by
The sham control group was enrolled to assess the ef- the same licensed acupuncturist, who has seven years’
fect of needle insertion into the skin. The simulated con- experience. However, clinical assessments of patients
trol group was used to define the psychological effects were evaluated by another researcher who was un-
of acupuncturetherapy. awareofthetreatment groups.
In the ShG, 18 needles, the same size as the AcG’s In addition, an experimental setup was used to provide
needles, were inserted into 18 sham points that are not eligible blinding of a patient to the kind of treatment
617
Karatay etal.
groups. This apparatus was very simple and useful for
clinical trials. The cost of the apparatus was low be-
cause it already exists in most hospitals. A three-section
folding screen for the hospital was used. First, the cur-
tain of the first section was removed from the bottom
pipe. Second, the foldable head section of an examina-
tiontable waspassedthroughthis sectionoftheframe.
After that, the patient sat on the examination table.
Needles were inserted or placed on Du-14 and Si-15
D
acupoints or near sham points according to treatment o
w
groups. Then the patient reclined in a position whereby n
lo
the needles in Du-14 and Si-15 acupoints or near sham a
d
e
points corresponded to the hollowness between the d
foldable head and body sections of the table (but not to fro
m
table surface). In addition, these needles were checked h
to ensure that they did not touch the table. The curtain ttp
wanitdh bthoedyfr.eeThloewreeforreen,dthweapsarteielenatswedasbentowteaebnlethteofaocbe- Fscigreuerne. P3atieBnltinsdcinagn nooftpoabrsteicrivpeanthtseirvtiareactumretanints.of the s://ac
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serve the treatment procedure (Figure 3). After that, the d
e
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treatment was performed according to the patient’s measured with commercial kits using the enzyme- ic
group. immunoassay(EIA)method. .o
u
p
.c
Three kinds of treatments were conducted semiweekly Statistical Analysis om
for four weeks, for a total of eight sessions. Each ses- /p
a
sionlasted30minutes. Needleswerenotmanipulated. Statistical analysis was performed with the SPSS 18.0 in
m
packet program for Windows. The repeated-measures e
d
Assessmentsand Measurements analysis of variance (RMANOVA) was used to determine ic
in
groupeffects(AcG,ShG,SiG),within-subjecteffects,and e
Plaasttientrtesatwmeernet,cliannicdallyatasosneessaenddatthbreaeselmineo,ntahfsterafttheer isnutemrapctitoionnswbaestwecehnecgkroeudpswainthd tiMmaeu.cThhlye’ssphteesritc,ityaansd- /article
the completion of all treatments. Clinical outcomes were Gerainhause-Geisser P values were used. One-way -a
b
peraainl,heNaTltPh,sctalitnuicsa.l assessments, depression, and gen- AteNstOsVwAearenduTsuekdeytohodneetesrtmsiingenifidciaffnetrednifcfeersenfocrespeorsottohnoinc strac
and SP levels among groups. Comparisons of data were t/19
Generalized widespread pain was measured by the vi- examined within groups by paired-samples t test. Also, /3/6
sual analog scale (VAS; 0 ¼ no pain, 10 ¼ the most correlations between serum markers and clinical data 1
5
intense pain). The Fibromyalgia Impact Questionnaire were evaluated by the Pearson correlation test. Values /4
6
(FIQ) was used for FM clinical assessment. This stan- withP<0.05weredeemedstatisticallysignificant. 89
dardized and validated tool has been translated into 18
1
Turkish and validated [30]. Also, general health status Results b
y
was assessed by Nottingham Health Profile (NHP). NHP g
u
is designed to measure health-related quality-of-life Seventy-five female patients with FM were enrolled in e
s
dimensions, such as emotional, social, and physical the study. However, seventy-two patients completed t o
n
health. It has six dimensions, including pain, energy, thestudy.Onesubject ineachofAcGandSiGdropped 2
7
physical mobility, emotional reactions, social isolation, out for individual reasons. Also one participant in the M
andsleep. Eachsubscalescoreisusedforassessment. SiG was removed from the study because she did not a
rc
The validity and reliability of the Turkish version of NHP continue to attend treatment sessions (Figure 4). There h
2
has been performed by Kucukdeveci et al. [31]. FM is a were no serious adverse effects in any of the three 0
1
chronic disease and may be easily affected by emo- groups. Only some patients experienced discomfort and 9
tional changes. Therefore, depression status was also bruising at the sites of needle insertion, especially in the
evaluated by Beck Depression Inventory (BDI). The BDI, ShG. However, patients tolerated it well and did not
including 21 items, was translated into Turkish; it was complain abouttheadverse effects.
validated in1998[32].
When demographic characteristics of the patients were
In addition to clinical assessments, serum serotonin and analyzed, the mean ages were found to be
SP levels were measured. Venous blood samples were 34.7166.09, 34.2066.84, and 35.1767.08years in
obtained at baseline and after the completion of all the AcG (N¼24), ShG (N¼25), and SiGs (N¼23), re-
treatments. Serum samples were stored at –80(cid:3)C until spectively. Also, mean BMI scores were 26.4965.65,
analyzed. The serum serotonin and SP levels were 26.9464.63, and 26.7364.61kg/m2. Patients had
618
Acupuncturein Fibromyalgia
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Figure4 Participant flow diagram. /p
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mean disease durations of 4.4463.99, 3.9463.30, In addition, there was no significant relationship be- in
e
and 5.0963.39years, respectively. There were no sig- tween baseline serum markers and the clinical parame- /a
nificant differences in terms of age, BMI, or disease ters (Table 3). However, some negative correlations rtic
durationsforpatients amongthegroups(P>0.05). were found between the change in serum markers and le
-a
thechange inotherparametersinthe ShG(Table4). b
s
In the AcG, significant improvements were found in tra
NTP, VAS, FIQ, and BDI scores, as well as some sub- Discussion ct/1
scales of NHP, after treatment (Tables 1 and 2). These 9
/3
improvements usually continued by the three-month Serotonin is a very important neurotransmitter for sleep, /6
1
mark. In the ShG, significant changes were observed in temperature, depression-anxiety, feelings, sexual behav- 5
/4
NTP, VAS, FIQ, and BDI scores after treatment. These ior, and pain regulation [5,33]. Also, different pharmaco- 6
8
improvements continued for NTP and FIQ scores for logic agents that increase serotonin are used effectively 9
1
three months. In the SiG, significant improvements were in the treatment of FM. SP is a neuropeptide and is re- 81
found only in the NTP, VAS, and BDI scores after lated to pain, depression, nausea-vomiting at the central b
y
treatment. They were not observed by the following nervoussystem,andneurogenicinflammationatthepe- g
u
assessments. ripheral nervous system [34]. Several medicines that are es
used in FM treatments, such as pregabalin, cause an t o
n
When group and time effects were analyzed by analgesiceffectviaSP[35]. 2
7
RMANOVA, with respect to time (from baseline to three M
a
months), changes in mean VAS, NTP, FIQ scores, BDI In addition, some nonpharmacological therapies such rc
scores, and some NHP subscales of the AcG were as massage therapy and aerobic exercise may also lead h 2
significantly different from both of the other groups to increases in serotonin and to decreases in SP levels 01
9
(Figure5,A–D). in pain reduction in FM [36,37]. However, the effect
mechanism behind acupuncture in FM treatment
Serum serotonin values increased significantly after remains unclear. We found only one clinical study inves-
treatment in the AcG and ShG (P<0.001 and P<0.01, tigating the effects of acupuncture therapy on serotonin
respectively) (Figure 6). The increase in the AcG was and SP levels in FM. However, it was not an RCT.
also different from both of the other groups (P<0.01). Sprott et al. [24] performed six sessions of individual
Serum SP levels decreased significantly in the AcG acupuncture therapy for six weeks in 29 patients with
(P¼0.001). However, while the levels increased in the FM. They evaluated pain with VAS and the NTP and
SiG (P¼0.001), they did not change in the ShG after assessedserumSPvaluesandserumandplateletsero-
treatment (Figure 7). The increase in the SiG was differ- tonin levels. They found significant improvements in pain
entfromboththe AcGandShG. and the NTP, a decrease of serotonin levels of platelets,
619
Karatay etal.
Table 1 The comparison of clinical parameters within groups and between groups at pre- and post-
treatment and at follow-up
AcG(N¼24) ShG(N¼25) SimG(N¼23) PAcG-ShG PAcG-SimG
VAS
Baseline 8.1062.52 7.7361.98 8.7361.25 >0.05 >0.05
After treatments 4.7062.53***** 6.7462.08*** 7.7561.40**** 0.003 <0.001
1moafter treatment 4.1162.46***** 6.8662.68 8.1961.45 <0.001 <0.001
3moafter treatment 4.4762.62***** 7.0162.70 8.2061.86 0.001 <0.001 D
o
Numberoftenderpoints w
n
Baseline 15.8862.80 15.8862.40 15.6162.64 >0.05 >0.05 lo
a
After treatments 4.9263.40***** 12.6464.78**** 13.8363.77** <0.001 <0.001 d
e
13mmooaafftteerr ttrreeaattmmeenntt 78..00486633..5929********** 1133..16646644..5798******* 1144..09466633..3121* <<00..000011 <<00..000011 d from
FIQ h
Baseline 70.80612.47 65.89624.14 57.39625.37 >0.05 >0.05 ttps
After treatments 40.60616.50***** 59.59625.18* 55.68624.47 0.011 >0.05 ://a
c
1moafter treatment 41.09620.19***** 59.57623.83* 55.80621.51 0.012 >0.05 a
d
3moafter treatment 43.64618.20***** 58.41622.38* 55.58619.72 0.034 >0.05 em
BDI ic
.o
Baseline 37.58618.81 36.64616.71 34.35615.74 >0.05 >0.05 u
p
After treatments 12.63612.24***** 27.32617.33*** 28.96616.12*** 0.004 0.002 .co
m
1moafter treatment 11.00610.58***** 27.28618.75*** 33.70616.09 0.001 <0.001 /p
3moafter treatment 10.1368.18***** 31.36618.44 35.35615.28 <0.001 <0.001 a
in
m
e
AcG¼acupuncture group; BDI¼Beck depression inventory; FIQ¼Fibromyalgia Impact Questionnaire; ShG¼sham group; d
ic
SimG¼simulatedgroup;VAS¼visualanalogscale. in
e
*P<0.05. /a
**P¼0.01. rtic
***P<0.01. le
-a
****P¼0.001. b
s
*****P<0.001;significancelevelincomparisonwithbaselinevaluesineachgroup. tra
c
t/1
9
/3
and an increase in serum SP and serotonin values. emotions, it did not change with noninserted placebo /6
1
5
However, that study had some limitations. First, it did acupuncture in the SiG. The second important result /4
6
not include a control group. Therefore, it was very diffi- was regarding the levels of SP changes. While SP levels 8
9
cult to determine whether the improvements and decreased in the AcG, they increased in the SiG. This 1
8
changes in serotonin and SP values were related to result seems to depend on real acupuncture effects 1 b
acupuncture efficacy or not. In addition, there were no rather than on the effects of needle insertion or place- y g
particular clinical parametersorvalidated indicesregard- bos. In addition, increased serotonin values may also ue
s
ingFM,exceptpain andtheNTPevaluations. have contributed to the reduction of SP levels in the t o
AcG. An inverse relationship between serotonin and SP n 2
Our study was a double-blinded RCT. We aimed to in- may occur in FM. Serotonergic neurons play an inhibi- 7 M
vestigate whether acupuncture had an effect on symp- tory role, especially in spinal pain pathways [6]. An in- a
toms andserum levelsof serotonin and SPin the study. crease of serotonin concentrations with a stimulus in rch
We hypothesized that acupuncture efficacy on symp- the periphery decreases SP expression in the spinal 20
1
toms and clinical parameters may be associated with cord [38]. Therefore, an increase of serotonin levels with 9
changes in the levelsof pain-modulating substances,in- acupuncture therapy may have affected the SP levels of
cluding serotonin and SP, in the treatment of FM. In this our patients. The intermediate increase of serotonin due
study, serotonin levels increased significantly with AcG to the insertion of the needle in the ShG may be insuffi-
and ShG. As changes were more prominent in the AcG cient tosuppressSPlevels.
than in the ShG, the increase of serotonin levels may
depend not only on the insertion of the needle, but also The relationship between the values of serotonin and
onthespecificeffectsof realacupuncture. SP and the clinical parameters of FM has been investi-
gated in clinical studies. Schwarz et al. [39] found a
Some interesting results were found in this study. First negative correlation between serum SP and serotonin
of all, although serotonin is known to be related to values in FM. While high concentrations of SP were
620
Acupuncturein Fibromyalgia
Table 2 The comparison of NHP subscale scores within groups and between groups at pre- and
post-treatment and at follow-up
AcG(N¼24) ShG(N¼25) SimG(N¼23) PAcG-ShG PAcG-SimG
NHPpain
Baseline 82.56628.00 65.22630.53 67.92632.66 >0.05 >0.05
After treatments 19.72631.94***** 53.49635.07* 46.55634.24*** 0.002 0.022
1moafter treatment 18.30630.36***** 55.68636.64 73.42632.17 0.001 <0.001
3moafter treatment 18.64629.90***** 57.90639.31 72.28633.71 0.001 <0.001 D
o
NHPphysicalmobility w
n
Baseline 46.64629.00 41.17628.91 43.88631.81 >0.05 >0.05 lo
a
After treatments 20.66629.00** 32.17630.13 45.54632.21 >0.05 0.018 d
e
13mmooaafftteerr ttrreeaattmmeenntt 1185..0491662255..4288********* 3343..2102663302..7997 4582..9891663327..1861 >>00..0055 00..000021 d from
NHPenergy h
Baseline 80.86635.47 69.20643.92 64.49645.74 >0.05 >0.05 ttps
After treatments 28.81638.94***** 53.54646.55 60.03643.36 >0.05 0.041 ://a
c
1moafter treatment 29.30643.25***** 63.93646.11 75.34639.04 0.017 0.001 a
d
3moafter treatment 29.30643.25***** 69.73645.07 71.41640.88 0.005 0.004 em
NHPsleep ic
.o
Baseline 59.76636.06 54.40634.30 58.94635.31 >0.05 >0.05 u
p
After treatments 23.30634.86*** 41.13636.08* 51.14636.83 >0.05 0.026 .co
m
1moafter treatment 12.73626.04***** 40.10635.49*** 59.95638.91 0.017 <0.001 /p
3moafter treatment 9.70619.95***** 47.91638.24 63.32638.62 <0.001 <0.001 a
in
NHPsocialisolation m
e
Baseline 57.97638.95 47.59637.51 54.78638.70 >0.05 >0.05 dic
After treatments 18.82628.39**** 31.81635.68* 48.11641.63 >0.05 0.017 in
e
1moafter treatment 8.71615.18***** 31.99640.71* 52.88638.95 0.048 <0.001 /a
3moafter treatment 8.08615.10***** 28.98639.46*** 48.78638.84 >0.05 <0.001 rtic
le
NHPemotionalreactions -a
b
Baseline 80.46630.77 58.51642.74 61.90641.70 >0.05 >0.05 s
After treatments 21.01628.78***** 49.33642.19 59.64636.48 0.022 0.001 trac
1moafter treatment 17.67626.73***** 58.65637.99 56.49639.07 <0.001 0.001 t/1
9
3moafter treatment 20.58628.44***** 56.43642.76 59.32640.95 0.004 0.002 /3
/6
1
5
AcG¼acupuncturegroup;NHP¼NottinghamHealthProfile;ShG¼shamgroup;SimG¼simulatedgroup. /4
6
*P<0.05. 8
9
**P¼0.01. 18
1
***P<0.01. b
****P¼0.001. y g
*****P<0.001;significancelevelincomparisonwithbaselinevaluesineachgroup. ue
s
t o
n
2
7
related to sleep abnormalities, there was no correlation Also, serum serotonin and SP levels were assessed to M
between serotonin levels and clinical parameters. Also, determine the peripheral effectiveness of acupuncture in arc
Yunus et al. [8] reported a negative correlation between this study. Serum serotonin and SP values may not al- h
2
plasmatryptophanlevelsandbothpainanddailystress. ways have a correlation to levels in the CNS. Further 0
1
However, Dessein et al. [40] did not find any association well-designed RCTs are needed to investigate the 9
between serum serotonin levels and the FIS scale. Also, effects of acupuncture on peripheral and central seroto-
Wolfe et al. [7] showed an association between serum ninandSPvaluesinpatients with FM.
serotonin values and clinical parameters, such as de-
pression and tender point count. In our study, no corre- Some clinical trials in acupuncture have reported benefi-
lation was found either between clinical assessments or cial improvements in the treatment of FM. However, the
serum markers. These controversial results may be at- quality of the trials is poor and the risk of bias is high,
tributed to the differences in measurement methods of according to a recent systematic review [41]. There are
serotonin and SP values, such as high-performance liq- few RCTs for acupuncture therapy in FM, and contro-
uid chromatography, enzyme-linked immunosorbent versial results have been reported. Deluze et al. [42]
assay, and double antibody radioimmunoassay. conducted an RCT study of 70 patients with FM
621
Karatay etal.
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Figure 5 The changes of the mean visual analog scores (A), the number of tender points (B), the Fibromyalgia 5
/4
Impact Questionnaire scores (C), and the Beck Depression Inventory scores (D) of the three groups depend on time. 6
8
9
BDI ¼BeckDepression Inventory;FIQ ¼Fibromyalgia Impact Questionnaire; VAS¼visual analog score. 1
8
1
b
y
including electroacupuncture and sham acupuncture usually occur in myofascial pain syndrome. However, g
u
groups. They found significant improvements in the pain there is not a trigger point in every patient with FM. e
s
threshold, the number of analgesics, pain scores, sleep, Local twitch response is observed when the trigger t o
n
and both the patients’ and the physicians’ global point is needling, but this response does not occur in 2
7
assessments in the electroacupuncture group vs the Ashi point acupuncture. The other issue is that the M
sham group. However, that study did not use any reli- authors compared 10 acupuncture sessions of one a
rc
able validatedtoolforFM.Also,therewasnofollow-up. group with five acupuncture sessions of the other group h
2
after 10weeks. As there was no follow-up to the study, 0
1
Itoh and Kitakoji [43] conducted a 10-session study of it is unknown whether or not the improvements in either 9
electroacupuncture vs a five-week control period and a groupwillcontinue.
five-session study of electroacupuncture for 16 patients.
They found significant improvements in pain intensity Assefi et al. [44] performed a well-designed RCT includ-
and quality of life in the pure electroacupuncture group ing 24 acupuncture sessions in FM. They chose three
in week 5. However, there were some limitations in that different sham and placebo groups for unrelated condi-
study. The subject size was very small in each group tions, needling on nonacupoint locations, or using non-
(N¼6 and N¼7). In addition, the acupuncturist per- inservative simulated acupuncture. As a result, the
formed both electroacupuncture and trigger point nee- effect of real acupuncture on pain did not differfrom the
dling for each patient. However, trigger point needling is three kinds of sham or placebo groups according to
different from Ashi point acupuncture. Trigger points that study. However, interventions were applied by eight
622
Acupuncturein Fibromyalgia
D
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Figure 6 Serum serotonin values at baseline and after ://a
c
completion of all treatments in the three groups. While Figure 7 Serum substance P values at the baseline ad
e
the white background represents levels of baseline, the and after completion of all treatments in three groups. m
black background represents levels after the treatments While the white background represents levels of the ic.o
in each group. *P¼0.002: the difference of serum sero- baseline, the black background represents levels after up
tonin levels after the treatments between acupuncture the treatments in each group. *P<0.001: the difference .co
m
and sham acupuncture groups. **P¼0.006: the differ- of serum substance P levels after the treatments be- /p
ence of serum serotonin levels after the treatments be- tween acupuncture and simulated acupuncture groups. ain
tween acupunctureand simulated acupuncturegroups. **P¼0.041: the difference of serum substance P levels m
e
after the treatments between sham acupuncture and dic
simulated acupuncturegroups. in
e
different acupuncturists in the study. Some RCTs and /a
meta-analyses reported that communication styles of rtic
le
the acupuncturists and expectation of benefits have im- their jaws, so they did not observe their treatments. It -a
portant roles in the effectiveness of both sham acu- was a very effective method in providing reliable blinding bs
puncture and real acupuncture [45–47], so varying and a realistic placebo treatment. However, it some- tra
c
attitudes of the eight therapists may affect the results. In times caused neck pain in patients. In addition, acu- t/1
9
our study, all interventions were performed by the same puncture treatment in a sitting position may cause more /3
acupuncturist. Also, as mentioned in the article by vasovagal symptoms than in the supine position. In our /61
5
Assefi, patients continued with their pharmacological study, another useful and inexpensive setup was used /4
6
and nonpharmacological treatments. Therefore, the for the blinding of participants in this study. It was the 8
9
benefits of other treatments may have had an unequal curtain of a hospital screen with three folding sections, 18
effect on the results in each group. Also, the results of so that the patients could not observe their own treat- 1 b
this study seem to reflect the effectiveness of adjunctive ment. In addition, while Martin et al. reported vasovagal y g
acupuncturebut notofacupuncturetreatment inFM. symptoms in two patients, patients did not experience ue
s
vasovagal symptoms in any of our groups. The supine t o
Martin et al. [48] conducted a well-designed RCT with position may prevent such adverse effects and can be n 2
50 patients. The acupuncture group received standard more relaxing than a sitting position. Therefore, we rec- 7 M
manual acupuncture and electroacupuncture for six ommend this simple setup to achieve reliable blinding of a
rc
sessions. They also added some acupoints during the participantsinacupuncture clinicaltrials. h
2
last three sessions. The control group was similar to our 0
1
simulated group. They used a nonpenetrating model These controversial results of acupuncture studies may 9
without electrical current as the control group. They be due to various factors: the selection of points, ther-
used the Multidisciplinary Pain Inventory and FIQ and apy frequency and durations, various follow-up dura-
followed patients for seven months after treatment. It tions, different style control groups such as sham,
was reported that treatment was primarily beneficial in simulated, and superficial acupuncture, and insufficient
pain, fatigue, and anxiety subscales, which they ob- blinding. The choice of a suitable placebo group is very
served one month after the treatment. The benefits did important for acupuncture RCTs. Some researchers
not have a significant outcome at the seven-month prefer using sham acupuncture in nonmeridian points or
mark. Also, they used a well-designed experimental unrelated acupoints in their trials. Others have used su-
setup to achieve blinding of participants. Patients were perficial needling in real acupuncture points in the con-
seated, and a screen and blanket were placed under trol group. However, even superficial needling on
623
Karatay etal.
Table 3 The correlations between baseline serum values of serotonin and substance P, and clinical
parameters
Serotonin,ng/mL SubstanceP,pg/mL
R P R P
VAS 0.018 0.881 (cid:4)0.130 0.278
Numberoftenderpoints (cid:4)0.209 0.078 (cid:4)0.102 0.393
FIQ (cid:4)0.219 0.065 (cid:4)0.108 0.365
D
BDI 0.123 0.302 0.096 0.421 o
w
NHPpain 0.093 0.439 0.026 0.831 n
lo
NHPphysicalmobility 0.006 0.962 (cid:4)0.052 0.664 a
d
NHPenergy (cid:4)0.119 0.318 (cid:4)0.008 0.944 ed
NHPsleep (cid:4)0.027 0.824 (cid:4)0.071 0.553 fro
m
NHPsocialisolation (cid:4)0.042 0.724 0.138 0.249
h
NHPemotionalreactions 0.089 0.463 0.115 0.342 ttp
s
BDI¼Beck depression inventory; FIQ¼Fibromyalgia Impact Questionnaire; NHP¼Nottingham Health Profile; VAS¼visual ://ac
a
analogscale. d
e
m
ic
.o
u
Table 4 The correlations between change in serum markers and change in clinical parameters p.c
o
m
AcG(N¼24) ShG(N¼25) SimG(N¼23) /p
a
in
DSerotonin, DSubstanceP, DSerotonin, DSubstanceP, DSerotonin, DSubstanceP, m
e
ng/mL pg/mL ng/mL pg/mL ng/mL pg/mL d
ic
in
e
DVAS R¼0.083 R¼(cid:4)0.228 R¼(cid:4)0.406 R¼(cid:4)0.079 R¼0.166 R¼0.043 /a
P¼0.700 P¼0.283 P¼0.044 P¼0.706 P¼0.449 P¼0.844 rtic
le
DNumberoftender R¼(cid:4)0.264 R¼(cid:4)0.143 R¼(cid:4)0.424 R¼(cid:4)0.304 R¼0.052 R¼(cid:4)0.021 -a
points P¼0.213 P¼0.506 P¼0.035 P¼0.139 P¼0.814 P¼0.923 bs
DFIQ R¼0.004 R¼(cid:4)0.285 R¼(cid:4)0.057 R¼0.250 R¼0.288 R¼(cid:4)0.161 tra
c
P¼0.987 P¼0.177 P¼0.787 P¼0.229 P¼0.182 P¼0.464 t/1
9
DBDI R¼0.009 R¼(cid:4)0.072 R¼(cid:4)0.525 R¼(cid:4)0.547 R¼(cid:4)0.002 R¼(cid:4)0.091 /3
P¼0.968 P¼0.738 P¼0.007 P¼0.005 P¼0.994 P¼0.679 /61
5
DNHPpain R¼0.162 R¼(cid:4)0.123 R¼(cid:4)0.380 R¼(cid:4)0.157 R¼(cid:4)0.252 R¼0.212 /4
6
P¼0.449 P¼0.566 P¼0.061 P¼0.453 P¼0.247 P¼0.332 8
9
DNHPphysical R¼(cid:4)0.114 R¼0.125 R¼(cid:4)0.472 R¼(cid:4)0.218 R¼(cid:4)0.252 R¼0.251 18
1
mobility P¼0.594 P¼0.562 P¼0.017 P¼0.296 P¼0.246 P¼0.248 b
y
DNHPenergy R¼(cid:4)0.239 R¼(cid:4)0.093 R¼(cid:4)0.201 R¼0.138 R¼0.065 R¼0.349 g
u
P¼0.260 P¼0.666 P¼0.336 P¼0.511 P¼0.768 P¼0.103 e
s
DNHPsleep R¼(cid:4)0.136 R¼(cid:4)0.077 R¼(cid:4)0.569 R¼(cid:4)0.393 R¼(cid:4)0.146 R¼(cid:4)0.152 t o
n
P¼0.527 P¼0.721 P¼0.003 P¼0.052 P¼0.506 P¼0.488 2
7
DNHPsocialisolation R¼(cid:4)0.112 R¼(cid:4)0.078 R¼(cid:4)0.436 R¼(cid:4)0.222 R¼(cid:4)0.215 R¼0.194 M
P¼0.601 P¼0.716 P¼0.030 P¼0.286 P¼0.325 P¼0.375 arc
DNHPemotional R¼(cid:4)0.218 R¼(cid:4)0.140 R¼(cid:4)0.183 R¼(cid:4)0.245 R¼(cid:4)0.003 R¼0.014 h 2
reactions P¼0.307 P¼0.514 P¼0.381 P¼0.237 P¼0.988 P¼0.948 01
9
D:valuesaftertreatment–baseline.
AcG¼acupuncturegroup;BDI¼Beckdepressioninventory;FIQ¼FibromyalgiaImpactQuestionnaire;NHP¼NottinghamHealth
Profile;ShG¼shamgroup;SimG¼simulatedgroup;VAS¼visualanalogscale.
acupoints or nonmeridian points may cause some acupuncture is chosen by acupuncturists in some RCTs
physiological response as some degree of acupuncture as a control as well. It can be performed by nonpene-
[49]. Therefore, sham acupuncture or superficial acu- trating placebo needles, toothpicks, and needling to an
puncture may not be inert intervention [50]. Simulated adhesive bandage but not the skin. However, even
624