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Review Article
The Immediate Analgesic Effect of Acupuncture for Pain:
A Systematic Review and Meta-Analysis
Anfeng Xiang, Ke Cheng, Xueyong Shen, Ping Xu, and Sheng Liu
Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Correspondence should be addressed to Sheng Liu; lskingcn@hotmail.com
Received 12 April 2017; Accepted 14 August 2017; Published 25 October 2017
Academic Editor: Shu-Ming Wang
Copyright © Anfeng Xiang et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Although acupuncture is gaining popularity for the treatment of nonspecic pain, the immediate analgesic eect of acupuncture
has never been reviewed. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) on disease-
related pain to critically evaluate the immediate eect of acupuncture for pain relief. e PubMed and Cochrane Central Register
of Controlled Trials databases as well as three Chinese databases including the China National Knowledge Infrastructure (CNKI),
Wanfang, and VIP platforms were searched through November . e outcome was the extent of pain relief from baseline within
min of the rst acupuncture treatment. We evaluated all RCTs comparing acupuncture with other interventions for disease-
related pain. Real acupuncture showed statistically signicantly greater pain relief eect compared to sham acupuncture (SMD,
−.; % condence interval [CI], −. to −.; RCTs) and analgesic injection (SMD, −.; % CI, −. to −.; RCTs).
No serious adverse events were documented. Acupuncture was associated with a greater immediate pain relief eect compared to
sham acupuncture and analgesic injections. Further RCTs with stricter design and methodologies are warranted to evaluate the
immediate pain relief eect of acupuncture for more disease-related pain.
1. Introduction
Pain is a major health problem with serious social and eco-
nomic consequences. e annual cost of pain management in
the USA in was – billion, which was a conserva-
tive estimate because it excluded the cost of management of
pain aecting institutionalized individuals []. Conventional
medical treatments are only moderately eective, and they
oen cause adverse side eects. A majority of people suering
pain in the USA and Europe have reported inadequate pain
control,andone-thirdworryaboutaddictiontopainmedica-
tions [, ]. Pain conditions appear to have a greater negative
impact on the factors aecting the quality of life, such as work
performance,sleep,andmood,comparedwithotherhealth
problems [, ]. Given the increasing life expectancy and
the aging population, appropriate management of pain and
reduction of disability are likely to assume greater impor-
tance.
Acupuncture, which is a mainstay in the healthcare prac-
tices of traditional Chinese medicine, is commonly used
for the treatment of pain. ere is substantial evidence for
acupuncture being eective in the treatment of acute [–]
and chronic pain []. To date, over systematic reviews have
been conducted to assess the role of acupuncture and related
therapies in the relief of pain. However, the results of these
systematic reviews are far from unanimous. e majority of
the reviews reported positive results for pain relief in low back
pain and osteoarthritis by acupuncture [–]. Two recent
systematic reviews [, ] examined the ecacy of acupunc-
ture in the relief of cancer-related pain, and both reported
positive results. e systematic review and meta-analysis by
Lu et al. suggested that acupuncture was useful in decreasing
postoperativepain[].However,theecacyofacupuncture
as a treatment of pain in other pain conditions such as neu-
ropathic pain [] or bromyalgia [] remains inconclusive.
Ernst et al. conducted a review of reviews [] and concluded
that acupuncture is not eective in reducing pain.
Various factors, such as acupuncture manipulation [,
], acupuncture sensation [], acupoint prescription [],
pathological status [], and types of pain [], can aect the
assessmentofthetherapeuticeectofacupuncture.edura-
tion of acupuncture stimulation and acupuncture paradigm
Hindawi
Evidence-Based Complementary and Alternative Medicine
Volume 2017, Article ID 3837194, 13 pages
https://doi.org/10.1155/2017/3837194
Evidence-Based Complementary and Alternative Medicine
as well as the assessment of analgesic eect following acu-
puncture treatment in dierent clinical trials have been
varied, and these time-dependent factors might be a crucial
determinant in evaluating the analgesic eect of acupuncture.
e eects of acupuncture can be classied as either the
immediate eects (immediately aer the end of the rst treat-
ment) or the cumulative eects of multiple acupuncture treat-
ments [, ]. To date, most clinical trials and systematic
reviews have focused on the cumulative analgesic eects. In
fact, immediate analgesic eect could have clinical signi-
cance in determining the ultimate ecacy of acupuncture in
pain management because of the following factors. () Psy-
chological components such as conditioning and expectation
may play important roles in acupuncture-induced analgesia.
Patients who receive little benet or no immediate analgesic
eect following the rst treatment might expect to be less
likely to gain benet from the subsequent treatment. () For
many patients with acute postoperative pain and labor pain,
the reported analgesic eect of acupuncture usually reects
the immediate eect. () e results of some fMRI studies
have suggested that the immediate and cumulative acupunc-
ture-induced analgesic eect elicit dierent temporal neural
responses in a wide range of brain networks [, ], suggest-
ing there is specic underlying mechanisms for the immedi-
ate analgesic eect of acupuncture.
To date, there is no published systematic review or meta-
analysis of the immediate analgesic eect of acupuncture.
erefore, we conducted a systematic review and meta-anal-
ysis to evaluate the immediate eect of acupuncture for vari-
ous disease-related pain in order to summarize the available
evidence, evaluate the quality of that evidence, and oer
suggestions for future research and treatment. is PRISMA-
compliant (Table S; see Table S in the Supplementary Mate-
rial available online at https://doi.org/.//)
systematic review was conducted with the following aims:
() to compare the immediate analgesic eect and safety of
acupuncture in the treatment of disease-related pain with
those of sham acupuncture and other active treatments; ()
to identify specic factors associated with positive results; and
() to identify areas for future treatment and research.
2. Materials and Methods
2.1. Search Strategy. Inthepresentstudy,weappliedthe
review methods advocated by the updated Cochrane Hand-
book for Systematic Reviews of Interventions []. e pro-
tocol of this systematic review has been registered in PROS-
PERO (http://www.crd.york.ac.uk/PROSPERO/DisplayPDF
.php? ID=CRD). We searched through the fol-
lowing databases to retrieve records from the earliest publi-
cations to those published till November , : PubMed/
MEDLINE, the Cochrane Central Register of Controlled Tri-
als, and three Chinese databases including the China National
Knowledge Infrastructure (CNKI), Wanfang, and VIP plat-
forms. Acupuncture-related terms including acupuncture,
electroacupuncture, and needle and pain-related terms
including pain, ache, and analgesia were used as the key
search terms in the English databases. e following key
terms were used in the Chinese digital databases: zhenjiu,
zhenci, dianzhen, zhen, and tong (which translate into acu-
puncture, needle-acupuncture, electroacupuncture, needle,
and pain, resp.). Our search was restricted to trials pub-
lished in English and Chinese. e reference lists of all
of the retrieved trials and reviews were screened; relevant
conference proceedings and abstracts as well as on-going
and unpublished studies were also manually searched. Two
reviewers independently evaluated each of the reports for
eligibility. Disagreements were resolved by discussion.
2.2. Inclusion Criteria. Studies that met the following criteria
were included in the present review: () randomized con-
trolled clinical trials; () trials comparing acupuncture with
sham acupuncture, no treatment, or eective western medi-
cations (e.g., anesthetics or analgesics); () studies including
participants suering from nonspecic pain; that is, there
were no restrictions on the type, cause, or duration of pain;
and () studies measuring self-reported pain relief using
scales such as the visual analogue scale (VAS), numeric rating
scale (NRS), or verbal rating scale (VRS). e outcome for
this review was pain relief immediately following the rst
treatment (i.e., less than or equal to min aer the end of
treatment) from the baseline level.
2.3. Exclusion Criteria. We exclude RCTs comparing dif-
ferent types of acupuncture among each other, or those
using transcutaneous electrical nerve stimulation (TENS) as
a treatment, or those of perioperative pain management, or
those using pressure/palpation pain as the unique outcome.
2.4. Data Collection and Analysis. Two authors (AX and KC)
independently extracted the study characteristics and out-
come data from the included studies. Disagreements between
the authors were resolved by discussion, and in case of
continued disagreement, a third reviewer (SL) was consulted.
Since the outcome for our review was the improvement in
pain immediately aer the end of the rst treatment, in case
of RCTs reporting the outcomes at multiple time points aer
treatment, we used the data at the time point closest to the end
of the treatment. In cases where only the nal and baseline
scores were available, we calculated the mean change of the
scorebysubtractingthemeannalvaluefromthemeanbase-
line value and computed the change-from-baseline standard
deviation using a correlation coecient []. In cases where
only the condence intervals (CIs) were available, we com-
puted the CIs for the mean values to calculate the standard
deviations []. In cases where the values were only available
in gures, we used a ruler to measure the value of the pain
outcomes. We combined the results of groups in which the
real acupuncture was adopted [] to create a single pairwise
comparison according to the Cochrane Handbook for Sys-
tematic Reviews of Interventions [].
2.5. Assessment of Risk of Bias in the Included Studies. For
each of the included studies, we assessed the risk of bias using
the Cochrane Collaboration’s risk of bias tool [], which
evaluates seven factors that might increase the risk of over-
or underestimating an intervention eect.
Evidence-Based Complementary and Alternative Medicine
In the assessment of the blinding of the participants and
assessors, we assigned sham-controlled trials a judgment of
“unclear” unless we were certain that the sham control was
convincing enough in fully blinding the participants to the
treatment being evaluated. We considered sham-controlled
trials as having a low risk of bias for blinding if the RCT either
(i) evaluated the credibility of the sham treatment and found
it to be indistinguishable from true acupuncture or (ii) used
a penetrating sham needle or a previously validated sham
needle (e.g., the Streitberger needle []). Two of the authors
(KC and AX) independently judged the risk of bias for each
domain. Any disagreement was resolved by discussion.
2.6. Assessment of Adequacy of Acupuncture. Tw o acupu n c-
turists (SL and XS) with a combined clinical experience of
nearly years in treating the pain syndrome with acupunc-
ture, and who had previously worked on RCTs of acupunc-
ture, assessed the adequacy of the acupuncture administered
in the trials. Four aspects of each acupuncture intervention
were assessed for adequacy: the choice of acupuncture points,
needling technique, duration of treatment, and experience
oftheacupuncturist[].etotalnumberofsessionsand
treatment frequency were not taken into account in the
assessment since, according to the denition of the immedi-
ate eect described above, only the rst treatment mattered
in the present study. e likelihood of the sham intervention
having physiological activity was also assessed by means of
an open-ended question. e acupuncturist assessors were
provided with only those parts of the publications that
described the acupuncture and sham procedures so that their
assessments could remain uninuenced by the results of the
trials. To test the success of blinding of the assessors to the
study publication and results, we asked the assessors to guess
the identity of each study being assessed. e acupuncturists
assessed the adequacies independently and achieved consen-
sus by discussion.
2.7. Data Synthesis and Statistical Analysis. We o n l y p ool e d
the data from the trials that used similar controls (e.g., sham
acupuncture, no treatment, or drug injection treatment). For
thepooleddata,thesummaryteststatisticswerecalculated
with the RevMan soware, version . [], using the random
eects model to account for the expected heterogeneity. We
evaluated the heterogeneity using the 𝐼2statistic [], which
indicates the proportion of variability across the trials not
explained by chance alone []. e statistical heterogeneity
was assessed using the 𝐼2statistic; an 𝐼2statistic value
of % or more was considered as indicating substantial
heterogeneity. All continuous data reported for all of the
studies were represented in forest plots. We did not carry out
meta-analysis when there were less than two studies in a com-
parison according to the denition of meta-analysis [].
We analyzed the penetrating and nonpenetrating sham
acupuncture-controlled trials separately; however, in cases
where there were no large or signicant dierences in the
pooled eect between these two subgroups of trials, we
pooled the data of all such trials available.
Two of the authors (AX and KC) independently graded
the overall quality of the evidence for each outcome using
the Grading of Recommendations Assessment, Development
and Evaluation (GRADE) classication [].
2.8. Measures of Treatment Eect. e major outcomes of the
review were the standardized mean dierences (SMDs) in the
pain outcomes between acupuncture and each of the control
groups.WeusedtheSMDsastheprincipalmeasureofeect
size because although the RCTs had assessed the same out-
comes, they had performed the measurements using dierent
scales (e.g., VAS and NRS).
2.9. Subgroup Analysis. We p er f o r m ed th e s u b g roup anal y s i s
of two clinical characteristics that might inuence the imme-
diate analgesic eect of acupuncture on pain: () the type
of sham, penetrating or nonpenetrating; () the duration of
pain, acute (≤ months) or chronic (>months)[].Weper-
formed statistical tests for interaction only if each subgroup
includedmorethanonestudy.Wecalculatedthe𝑃values,
pooled estimates, and 𝐼2values of each of the two relevant
subgroups for the subgroup comparisons of both character-
istics.
2.10. Sensitivity Analysis. Considering that clinical pain
included in present study was induced by various diseases, we
also conducted the sensitivity analysis using the leave-one-
out approach. e study by Zhang et al. [] was excluded for
further meta-analysis.
3. Results
3.1. Search Results. Figure outlines the procedure of search
and screening throughout the review. e initial electronic
database search identied potential studies of interest.
Aer screening these citations by their titles and abstracts, we
considered potentially eligible articles for inclusion and
retrieved the corresponding full articles. Of the studies,
wereexcludedbecauseoftheuseofothertypesofacu-
puncture as controls, improper denition of the immediate
eect, inaccurate protocols, or the quasi-random method of
allocating patients to each group alternately, leaving eligible
RCTs [–]. Tables and describe the trial characteristics
and the acupuncture and control interventions.
3.2. Characteristics of the Included Studies. We nally evalu-
atedatotalofstudiesincludingatotalof,participants
with a mean age of years (range, – years). For all of
theeligibleRCTs,theparticipantswererequiredtohavebeen
diagnosed with disease-related pain for eligibility. Of the
RCTs, investigated LBP [, , , ], and the remaining
investigated neck pain [], neck and shoulder pain [],
carpal tunnel syndrome (CTS) [], knee osteoarthritis [],
bromyalgia [], dysmenorrhea [], sore throat [], renal
colic [], and migraine []. e RCTs included in this
review used either the VAS or NRS to measure pain outcomes.
While RCTs [, , , –] used acupoints based
on the traditional Chinese medicine theory of meridians
andcollaterals,[,,,]usedtenderpointsnear
the most painful areas, and [] used points based on
Evidence-Based Complementary and Alternative Medicine
T : Characteristics of randomized controlled trials.
Study, year Country Disease 𝑁(M/F) Mean age∗
(year)
Acupuncture
(points; duration time) Control
Time point aer
treatment for
assessment
Pain
assessment
Chen and Li []
() China Renal colic (/) . (.) EA (KI, GB, BL, RN,
tender points; minutes)
Intramuscular
Fortanodyn injection min VAS
Inoue et al. []
() Japan Low back pain (/) . (.) MA (one most painful
point; seconds) Nonpenetrating SA Immediately VAS
Inoue et al. []
() Japan Low back pain (/) . (.) MA ( two to ve tender
points;seconds)
Local dibucaine
injection Immediately VAS
Liu et al. []
() China Dysmenorrhea (/) . (.) EA (SP; minutes) (1) EA at unrelated point
(2)EAatSP immediately VAS
Lu et al. []
() China Knee OA (unclear) . (.) EA (GB, SP, SP, ST,
ST; minutes) Sham EA at SPs Immediately VAS
Mejuto V´
azquez et al. []
() Spain Neck pain (/) . (.) DN (MTrPs; –
seconds) No treatment min NRS
Maeda et al. []
() USA CTS (/) . (.) EA (PC, TW or SP, LI;
more than minutes) Nonpenetrating SA Immediately VAS
Nabeta and Kawakita []
() Japan Neck and shoulder pain (/) . (.) MA (two to twelve tender
points; minutes) Nonpenetrating SA Immediately VAS
Shin et al. []
() Korea Low back pain (/) . (.)
Motion style acupuncture
(DU, LR, LI;
minutes)
Local diclofenac sodium
injection min NRS
Stival et al. []
() Brazil Fibromyalgia (/) . (.) MA (PC, HT, SP, LI,
LR, ST; minutes) Penetrating at SPs Immediately VAS
Su et al. []
() China Low back pain (/) . (.) MA (two ankle points;
minutes) Nonpenetrating SA Immediately VAS
Yang e t a l . [ ]
() China Sore throat (/) . (.)
MA (LI; removing the
needle aer eliciting the
sensation)
Penetrating at SP min VAS
Zhang et al. []
() China Migraine (/) . (.) EA (GB, SJ, GB, GB;
minutes) Penetrating at SPs Immediately NRS
Notes.∗Mean (standard deviation); CTS: carpal tunnel syndrome; DN: dry needling; EA: electroacupuncture; F: female; M: male; MA: manual acupuncture; 𝑁: number; SA: sham acupuncture; SP: sham acupoint.
Evidence-Based Complementary and Alternative Medicine
T:Riskofbiassummary.
Study, year Sequence
generation
Allocation
concealment
Participants and assessor
blinding
Treatment provider
blinding
Incomplete outcome
data addressed
Free of selective
reporting others
Chen and Li []
() Low Unclear [b]High[c]High Low Low Low
Inoue et al. []
() Low Low Low High Low Low Low
Inoue et al. []
() Low Unclear[b]High[c]High Low Low Low
Liu et al. []
() Low Low Low High Low Low Low
Lu et al. []
() Unclear[a]Uncle ar[b]Low High Low Low Low
Mejuto-V´
azquez et al. []
() Low Low High[d]High Low Low Low
Maeda et al. []
() Unclear[a]Uncle ar[b]Unclear[e]High Low Low High[f]
Nabeta and Kawakita []
() Low Unclear[b]Low High Low Low Low
Shin et al. []
() Low Low High[c]High Low Low Low
Stival et al. []
() Low Uncle ar[b]Low High Low Low Low
Su et al. []
() Low Low Low High Low Low Low
Yang e t a l . [ ]
() Low Low Low High Low Low Low
Zhang et al. []
() Low Low Low High Low Low Low
[a]Lu et al. and Maeda et al. RCT claimed to have randomly assigned participants but did not describe the methods in detail; [b]Chen and Li , Inoue et al. , Maeda et al. , Lu et al. , Nabeta
and Kawakita , and Stival et al. did not mention allocation concealment; [c]Chen and Li , Inoue et al. , and Shin et al. compared acupuncture versus analgesia injection, and the participants,
who were also the outcome assessors, could not be blinded; [d]Mejuto-V´
azquez et al. compared acupuncture versus no treatment, and the participants, who were also the outcome assessors, could not be
blinded; [e]Maeda et al. RCT used nonpenetrating sham acupuncture as control but did not evaluate the credibility of the sham; [f]forMaedaetal.RCT,thebaselinewasnotcomparableinthetwogroups.
Evidence-Based Complementary and Alternative Medicine
921 English records identied
through PubMed and Cochrane
1679 Chinese records identied
through Chinese databases
2586 records aer removing
duplicates
2586 records screened
2484 records unrelated to
acupuncture and immediate
analgesia from reading the
abstracts were excluded
102 full-text articles
assessed for eligibility
13 studies eligible for inclusion
13 studies included in qualitative and
quantitative synthesis (meta-analysis)
102 full-text articles were excluded with
reasons:
Controlled with other types of
acupuncture, sham laser, acupressure
(n=75)
Evaluated multiple treatments (n=6)
Blood-letting therapy (n=2)
TENS (n=3)
Protocol (n=2)
Quasi-RCT (n=1)
F : Flow diagram showing the number of studies included and excluded from the systematic review.
another acupuncture theory (i.e., the wrist-ankle acupunc-
ture method). Electroacupuncture was administered in
RCTs[,,,,]andmanualacupuncturein
RCTs [, , , –]. Of the RCTs that had used sham
acupuncture as a control, had used nonpenetrating sham
[, , , ] and had used penetrating sham [, , ,
, ]. Of the RCTs that had used analgesic injection as a
control, [, ] had administered intramuscular analgesic
injections and [] had administered a local anesthetic
injection. One of the included RCTs [] compared the eects
of acupuncture at distal and local points and sham acupunc-
ture; we, therefore, combined the results of the two real acu-
puncture groups to create a single pairwise comparison.
3.3. Acupuncture Adequacy. e acupoints and needling
techniques were judged as being adequate in all of the
includedtrials.Allofthetrialsincludedinthisreviewwere
judged to be adequate in terms of the treatment duration,
except for those by Maeda et al. [] and Yang et al. []. In
the RCT by Maeda et al., only the fMRI scan time ( min and
s) was known []. In the trial by Yang et al., the needle had
been inserted and removed quickly []. Neither of the trials
had reported the exact treatment durations, while the rest of
thetrialsincludedinthisreviewhad.Whiletheacupunc-
turists in of the trials [–, –] were judged as having
adequate experience, we were unclear about the experience of
the acupuncturists in the remaining trials [, , ] owing
to that fact that there is no description of the experience of
acupuncturists in these studies. e assessors of acupuncture
adequacy in this review were successfully blinded to all
included publications and were unable to distinguish the
origins of the results included.
3.4. Risk of Bias in the Included Studies. Of the trials
included in this review, [–, –, , ] were assessed
as having a low risk of bias upon sequence generation, while
the risks of bias of the remaining trials [, ] were
assessed as being unclear (Table , Figures S and S). e
RCTs by Lu et al. and Maeda et al. claimed to have randomly
assigned the participants but did not describe their methods
in detail [, ]. Nearly half (/) of the included trials did
notmentionallocationconcealment[,,,,,]
Evidence-Based Complementary and Alternative Medicine
Std. mean dierenceStd. mean dierence
1.1.2 Penetrating sham
Liu et al. 2014 (dysmenorrhea) −26.8 16.72 167 −22.4 17.85 167 13.5% −0.25 [−0.47, −0.04]
Lu et al. 2010 (knee osteoarthritis) −1.1 0.53 10 −0.565 0.4 10 8.4% −1.09 [−2.05, −0.14]
Stival et al. 2014 (bromyalgia) −4.36 3.23 21 −1.7 1.55 15 10.3% −0.97 [−1.68, −0.27]
Yang et al. 2012 (sore throat) −3.1 1.73 36 −1.35 1.74 38 11.9% −1.00 [−1.48, −0.51]
Zhang et al. 2015 (migraine) −1.84 0.63 55 −2.7 1.57 55 12.6% 0.71 [0.33, 1.10]
Subtotal (95% CI) 289 285 56.7% −0.46 [−1.11, 0.18]
Total (95% CI) 391 367 100.0% −0.56 [−1.00, −0.12]
−15
Study or subgroup
1.1.1 Nonpenetrating sham
Inoue et al. 2006 (low back pain) 9 15 9 16 9.8% −1.08 [−1.84, −0.32]
Maeda et al. 2013 (carpal tunnel syndrome) −1.2 1.82 40 −0.5 1.4 19 11.4% −0.41 [−0.96, 0.14]
Nabeta and Kawakita 2002 (neck and shoulder pain) −11 24.74 17 −7.3 26.02 17 10.5% −0.14 [−0.82, 0.53]
Su et al. 2010 (low back pain) −18.53 10.3 30 −6.7 9.3 30 11.4% −1.19 [−1.74, −0.64]
Subtotal (95% CI) 102 82 43.3% −0.70 [−1.21, −0.20]
−5
Verum acupuncture Sham acupuncture
Mean SD Total Mean SD Total We i gh t IV, random, 95% CIIV, random, 95% CI
Heteroge neity: 2= 0.16;2= 7.72,＞＠ = 3 (P = 0.05); I2=61%
Test for overall eect: Z = 2.74 (P = 0.006)
Heteroge neity: 2= 0.45;2= 40.09,＞＠ = 4 (P < 0.00001 ); I2= 90%
Test for overall eect: Z = 1.4 1 (P = 0.16)
Heteroge neity: 2= 0.36;2=54.99,＞＠ = 8 (P < 0.00001); I2=85%
Test for overall eect: Z = 2.5 0 (P = 0.01)
Test for subgroup dierences: 2= 0.34,＞＠ = 1 (P = 0.56), I2=0%
−1−2
Favors verum acupuncture
120
Favors sham acupuncture
F : Acupuncture versus sham acupuncture: pain. % CI, condence interval; Std., standardized.
and were, therefore, assessed as having unclear risk of bias
in this dimension. e remaining trials were assessed as
having a low risk of bias on allocation concealment. In one
of the sham-controlled trials [], we were not certain
whether the sham was distinguishable from true acupuncture
by the participants because this trial used nonpenetrating
sham acupuncture as a control, and the credibility of the sham
had not been mentioned or evaluated in previous literature.
e remaining sham-controlled RCTs [, , , , –
] had either used penetrating sham acupuncture or eval-
uated/mentioned nonpenetrating sham acupuncture in their
study and were therefore assessed as having a low risk of bias
on participant/assessor blinding. All of the included trials
were regarded as having a low risk of incomplete outcome
data (attrition bias) and selective reporting (reporting bias)
becauseallofthepatientshadcompletedthersttreatment
session as well as the posttreatment assessment, and there had
been no withdrawals.
3.5. Eects of Interventions
3.5.1. Acupuncture versus Sham Acupuncture. Real acupunc-
ture showed a greater immediate pain relief eect compared
to sham acupuncture (SMD, −.; % CI, −. to −.;
RCTs, Figure ). ere was a substantial heterogeneity of
results in these trials (𝐼2=85%).eresultsoftheGRADE
analysis indicated that the overall quality of evidence for this
outcome was moderate as a consequence of uncertain risk
of selection bias because of the nonavailability of detailed
descriptions of sequence generation and allocation conceal-
ment ( RCTs) and unclear risk of performance bias because
of uncertain blinding ( RCT).
3.5.2. Acupuncture versus Analgesic Injection. e results of
the comparative ecacy studies revealed that acupuncture
was associated with statistically signicantly greater imme-
diate pain relief compared to analgesic injection with non-
steroidal anti-inammatory drugs (NSAIDs) or local anes-
thetic (SMD, −.; % CI, −. to −.;RCTs;Figure).
ere was a substantial heterogeneity of results in these trials
(𝐼2=60%).eresultsoftheGRADEanalysisindicatedthat
the quality of evidence for this outcome was low as a con-
sequence of a high risk of performance and detection bias
because of inadequate data and the lack of blinding.
3.5.3. Acupuncture versus No Treatment. Acupuncture was
associated with statistically signicantly greater immediate
pain relief than no treatment (SMD, −.; % CI, . to
−.; RCT). e results of the GRADE analysis indicated
that the quality of evidence for this outcome was low as a
consequence of a high risk of performance and detection bias
because of inadequate data and the lack of blinding.
3.6. Subgroup Analysis. ere was no statistically signicant
dierence in the eect estimates between the two substrata for
either of the clinical characteristics, that is, the type of sham
(𝑃 = 0.56,Figure)andthedurationofpain(𝑃 = 0.92,
Figure ). e results did show that true acupuncture was
statisticallysignicantlymoreeectivethannonpenetrating
sham acupuncture (SMD, −.; % CI, −. to −.;
RCTs; 𝐼2=61%); however, the pooled result was not sta-
tistically signicant when compared with that of penetrating
sham acupuncture (SMD, −.; % CI, −. to .; RCTs;
𝐼2=90%). For the duration of pain, the results showed that
real acupuncture was statistically signicantly more eective
than sham acupuncture for chronic pain (SMD, −.; %
CI, −. to −.; RCTs; 𝐼2=50%);however,thepooled
result was not statistically signicant for acute pain (SMD,
−.; % CI, −. to .; RCTs; 𝐼2=95%).
Evidence-Based Complementary and Alternative Medicine
Chen and Li 2012 (renal conic)
Inoue et al. 2009 (low back pain)
Shin et al. 2013 (low back pain)
1.82−3.43 −1.92
−43.1 27
−3.83 2.05
26
13 −15.3
29 −0.71
1.26
20.4
1.06
25 37.3%
13 27.3%
29 35.4%
Std. mean dierence
−0.95 [−1.53, −0.37]
−1.13 [−1.96, −0.29]
−1.89 [−2.51, −1.26]
Std. mean dierence
Total (95% CI) 68 67 100.0% −1.33 [−1.94, −0.72]
Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% CI IV, random, 95% CI
Acupuncture Analgesic injection
Favors analgesic injection
Heterog eneity: 2= 0.17;2= 4.94,＞＠ = 2 (P = 0.08); I2=60%
Test for overall eect: Z = 4.26 (P < 0.0001 )−1012−2
Favors acupuncture
F : Acupuncture versus analgesic injection: pain. % CI, condence interval; Std., standardized.
Verum acupuncture Sham acupuncture Std. mean dierence Std. mean dierence
Mean SD Total Mean SD Total IV, random, 95% CI
2.1.1 Acute pain
−18.53 10.3 30 −6.7 9.3 30 11.4% −1.19 [−1.74, −0.64]
Yang et al. 2012 (sore throat) −3.1 1.73 36 −1.35 1.74 38 11.9% −1.00 [−1.48, −0.51]
Zhang et al. 2015 (migraine) −1.84 0.63 55 −2.7 1.57 55 12.6% 0.71 [0.33, 1.10]
Subtotal (95% CI) 121 123 36.0% −0.48 [−1.76, 0.80]
IV, random, 95% CI
2.1.2 Chronic pain
Inoue et al. 2006 (low back pain) −15 9 15 −5 9 16 9.8% −1.08 [−1.84, −0.32]
Liu et al. 2014 (dysmenorrhea) −26.8 16.72 167 −22.4 17.85 167 13.5% −0.25 [−0.47, −0.04]
−1.1 0.53 10 −0.565 0.4 10 8.4% −1.09 [−2.05, −0.14]
Maeda et al. 2013 (carpal tunnel syndrome) −1.2 1.82 40 −0.5 1.4 19 11.4% −0.41 [−0.96, 0.14]
Nabeta and Kawakita 2002 (neck and shoulder pain) −11 24.74 17 −7.3 26.02 17 10.5% −0.14 [−0.82, 0.53]
Stival et al. 2014 (bromyalgia) −4.36 3.23 21 −1.7 1.55 15 10.3% −0.97 [−1.68, −0.27]
Subtotal (95% CI) 270 244 64.0% −0.54 [−0.88, −0.21]
Total (95% CI) 391 367 100.0% −0.56 [−1.00, −0.12]
Favors sham acupuncture
Heteroge neity: 2= 1.21;2= 44.24,＞＠ = 2 (P < 0.00001 ); I2=95%
Test for overall eect: Z = 0.7 4 (P = 0.46)
Heteroge neity: 2= 0.08;2= 9.95,＞＠ = 5 (P = 0.08); I2=50%
Test for overall eect: Z = 3.22 (P = 0.001 )
Heteroge neity: 2= 0.36;2=54.99,＞＠ = 8 (P < 0.00001); I2=85%
Test for overall eect: Z = 2.5 0 (P = 0.01)
Test for subgroup dierences: 2= 0.01,＞＠ = 1 (P = 0.92), I2=0%
Su et al. 2010 (low back pain)
Lu et al. 2010 (knee osteoarthritis)
Wei g htStudy or subgroup
−1 0 1 2−2
Favors verum acupuncture
F : Subgroup analysis with the duration of pain (acute versus chronic) for sham-controlled trials. % CI, condence interval; Std.,
standardized.
3.7. Sensitivity Analysis. As shown in Table , heterogeneity
of sham-controlled meta results decreased (𝐼2=68%) when
the study by Zhang et al. [] was excluded. Real acupuncture
consistently showed a greater immediate pain relief eect
compared to sham acupuncture and drug injection by exclud-
ing Zhang et al.’s study (SMD, −.; % CI, −. to −.;
RCTs, Figure ) or each of the other included ones. Aer
excluding the study by Zhang et al., subgroup meta-analysis
showed that real acupuncture was better than penetrating
sham in terms of the ecacy of pain relief (SMD, −.; %
CI, −. to −.; RCTs, 𝐼2= 75.8%, Figure ), and acu-
puncture was more eective than the sham acupuncture in
reducingacutepain(SMD,−.; % CI, −. to −.;
RCTs, 𝐼2=0%, Figure ). e heterogeneity of present study
seemstobemainlyfromtheZhangetal.’sstudy.
3.8. Safety of Acupuncture. A total of trials had included
descriptions of adverse events associated with acupuncture
[,,,,,–].Sevenofthesetrialsreported
no adverse events following acupuncture treatment; only Liu
et al. [] reported a small hematoma in one of the patients in
their acupuncture group and a small hematoma and needling
pain experienced, respectively, in one patient in their pene-
trating sham acupuncture group. No serious adverse events
were reported in any of the trials.
4. Discussion
is is the rst systematic review and meta-analysis of RCTs
on the immediate eects of acupuncture for the treatment of
disease-related pain. We included a total of studies in our
review. e results showed statistically signicant dierences
between the ecacy of real acupuncture and those of sham
controlsforalltypesofpainincludedinthisreview.e
SMDs between real acupuncture and control sham acupunc-
ture were lower than those between real acupuncture and a
no-acupuncture control. In addition, acupuncture appeared
to be more eective than analgesic injection (at intragluteal
site with analgesic or local inltration with anesthetic) in
reducing pain. e meta-analytic eect sizes were not sim-
ilar across pain conditions. ere was no evidence of any
signicant harm caused by acupuncture in any of the RCTs.
However, it should be stressed that this lack of evidence is
based on the results of a few small trials with a high risk of
Evidence-Based Complementary and Alternative Medicine
T : Sensitivity analysis of included studies.
Study, year Statistics with study removed
Dierence in means Lower limit Upper limit 𝑍-value 𝑃value 𝐼2
Acupuncture versus sham acupuncture
Inoue et al. −0.5 −0.97 −0.04 . . %
Maeda et al. −0.58 −1.08 −0.09 . . %
Nabeta and Kawakita −0.61 −1.10 −0.13 . . %
Su et al. −0.47 −0.93 −0.02 . . %
Liu et al. −0.62 −1.20 −0.04 . . %
Lu et al. −0.51 −0.97 −0.05 . . %
Stival et al. −0.51 −0.98 −0.04 . . %
Yang e t a l . −0.50 −0.97 −0.03 . . %
Zhang et al. −0.72 −1.06 −0.38 . <. %
Acupuncture versus analgesic injection
Chen and Li −1.56 −2.30 −0.82 . <. %
Inoue et al. −1.41 −2.33 −0.49 . . %
Shin et al. −1.00 −1.48 −0.53 . <. %
1.1.1 Nonpenetrating sham
Inoue et al. 2006 (low back pain) −15 9 15 −5 9 16 10.1%
Maeda et al. 2013 (carpal tunnel syndrome) −1.2 1.82 40 −0.5 1.4 19 13.3%
Nabeta and Kawakita 2002 (neck and shoulder pain) −11 24.74 17 −7.3 26.02 17 11.3%
Su et al. 2010 (low back pain) −18.53 10.3 30 −6.7 9.3 30 13.3%
Subtotal (95% CI) 102 82 48.0%
1.1.2 Penetrating sham
Liu et al. 2014 (dysmenorrhea) −26.8 16.72 167 −22.4 17.85 167 18.9% −0.25 [−0.47, −0.04]
Lu et al. 2010 (knee osteoarthritis) −1.1 0.53 10 −0.565 0.4 10 7.8% −1.09 [−2.05, −0.14]
Stival et al. 2014 (bromyalgia) −4.36 3.23 21 −1.7 1.55 15 10.9% −0.97 [−1.68, −0.27]
Yang et al. 2012 (sore throat) −3.1 1.73 36 −1.35 1.74 38 14.4% −1.00 [−1.48, −0.51]
Subtotal (95% CI) 234 230 52.0% −0.75 [−1.27, −0.23]
Std. mean dierence Std. mean dierence
Total (95% CI) 336 312 100.0% −0.72 [−1.06, −0.38]
Verum acupuncture Sham acupuncture
Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% CI IV, random, 95% CI
−1.08 [−1.84, −0.32]
−0.41 [−0.96, 0.14]
−0.14 [−0.82, 0.53]
−1.19 [−1.74, −0.64]
−0.70 [−1.21, −0.20]
Favors verum acupuncture
Heteroge neity: 2= 0.16;2= 7.72,＞＠ = 3 (P = 0.05); I2=61%
Test for overall eect: Z = 2.74 (P = 0.006)
Heteroge neity: 2= 0.19;2= 11.96,＞＠ = 3 (P = 0.008 );I2=75%
Test for overall eect: Z = 2.84 (P = 0.005 )
Heteroge neity: 2= 0.15;2= 21.70,＞＠ = 7 (P = 0.003); I2= 68%
Test for overall eect: Z = 4.17 (P < 0.0001 )
Test for subgroup dierences: 2= 0.02,＞＠ = 1 (P = 0.89), I2=0%
−1 0 1 2−2
Favors sham acupuncture
F : Subgroup analysis with the type of sham (nonpenetrating versus penetrating) for sham-controlled trials (excluding study by Zhang
et al. []). % CI, condence interval; Std., standardized.
bias. erefore, a careful interpretation is warranted before
arriving at a positive conclusion.
Compared with the assessment of the cumulative eects
of acupuncture, the determination of the immediate eects
could be relatively easy; that is, it is not necessary to consider
the treatment endpoint or follow-up duration. Acupuncture
alsohasaverylowdrop-outrate.Forthesystematicreview
and meta-analysis of the ecacy of acupuncture, various
factors could aect the outcomes in the evaluation of the
cumulative eects of acupuncture, including the total number
of treatment sessions, treatment period, and variation in the
end points, such as those of pain and function measurements
at dierent times. Because of the exclusion or minimization of
thesevariablefactors,theevaluationoftheimmediateeect
may closely reect the actual analgesic eects of acupuncture
stimulation.
Primary analgesic agents, such as morphine, can be used
for the management of both acute and chronic pain. e peak
eect of morphine is at around min when administered
intravenously and at min when administered orally, while
the duration of its eect is between and h [, ]. e
results of our systematic review and meta-analysis indicate
that acupuncture shows an immediate analgesic eect as the
treatment of chronic pain. In general, the duration of onset of
theeectofacupunctureis–min[,].edurationof
the analgesic eect following a single session of acupuncture
is about days, although this duration is not consistent [].
erefore, the immediate eect of acupuncture may have
Evidence-Based Complementary and Alternative Medicine
2.1.1 Acute pain
Su et al. 2010 (low back pain) −18.53 10.3 30 −6.7 9.3 30 13.3% −1.19 [−1.74, −0.64]
Yang et al. 2012 (sore throat) −3.1 1.73 36 −1.35 1.74 38 14.4% −1.00 [−1.48, −0.51]
Subtotal (95% CI) 66 68 27.7% −1.08 [−1.45, −0.72]
2.1.2 Chronic pain
Inoue et al. 2006 (low back pain) −15 9 15 −5 9 16 10.1% −1.08 [−1.84, −0.32]
Liu et al. 2014 (dysmenorrhea) −26.8 16.72 167 −22.4 17.85 167 18.9% −0.25 [−0.47, −0.04]
Lu et al. 2010 (knee osteoarthritis) −1.1 0.53 10 −0.565 0.4 10 7.8% −1.09 [−2.05, −0.14]
Maeda et al. 2013 (carpal tunnel syndrome) −1.2 1.82 40 −0.5 1.4 19 13.3% −0.41 [−0.96, 0.14]
Nabeta and Kawakita 2002 (neck and shoulder pain) −11 24.74 17 −7.3 26.02 17 11.3% −0.14 [−0.82, 0.53]
Stival et al. 2014 (bromyalgia) −4.36 3.23 21 −1.7 1.55 15 10.9% −0.97 [−1.68, −0.27]
Subtotal (95% CI) 270 244 72.3% −0.54 [−0.88, −0.21]
Total (95% CI) 336 312 100.0% −0.72 [−1.06, −0.38]
Std. mean dierence Std. mean dierenceVerum acupuncture Sham acupuncture
Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% CI IV, random, 95% CI
Favors sham acupuncture
Heteroge neity: 2= 0.00;2= 0.26,＞＠ = 1 (P = 0.61); I2=0%
Test for overall eect: Z = 5.82 (P < 0.00001 )
Heteroge neity: 2= 0.08;2= 9.95,＞＠ = 5 (P = 0.08); I2=50%
Test for overall eect: Z = 3.22 (P = 0.001 )
Heteroge neity: 2= 0.15;2= 21.70,＞＠ = 7 (P = 0.003); I2=68%
Test for overall eect: Z = 4.17 (P < 0.0001 )
Test for subgroup dierences: 2= 4.57,＞＠ = 1 (P = 0.03), I2= 78.1%
−1 0 1 2−2
Favors verum acupuncture
F : Subgroup analysis with the duration of pain (acute versus chronic) for sham-controlled trials (excluding study by Zhang et al. []).
% CI, condence interval; Std., standardized.
clinical signicance as an alternation for analgesic medication
or as a reasonable method for pain treatment. Moreover, the
success of acupuncture as a treatment of pain is oen gauged
by the number of clients retained in pain management or
treatment facilities. e apparent benets of the immediate
analgesic eect of acupuncture may entice patients to receive
long-term acupuncture treatment willingly or open to other
forms of acupuncture options. erefore, the immediate suc-
cess of acupuncture treatment should not be overestimated.
In present study, we did not nd a greater immediate pain
relief eect of acupuncture for acute pain compared with the
sham acupuncture (𝑃 = 0.46). However, our sensitivity anal-
ysis showed that real acupuncture was more eective than
the sham acupuncture in reducing acute pain immediately,
if excluding the study by Zhang et al. []. is might be
explained by some variable factors, such as the types of sham
acupuncture, control procedures, and outcome measures.
Further rigorous studies with standardized methodologies
are required to test the ecacy of acupuncture for the
treatment of acute pain.
e design of a control group is a continuing challenge for
clinical trials of acupuncture. Many clinical trials were unable
to detect statistically signicant dierences in the treatment
ecacies between their acupuncture treatment and control
groups in terms of any of the outcome measurements [–
]; the authors of these trials concluded that acupuncture
was no more eective than any sham interventions, for exam-
ple, skin-touch sham (nonpenetrating) and skin-penetration
sham in reducing pain. Based on the results of this systemic
review and meta-analysis study, we found real acupuncture
treatment has statistically signicantly greater immediate
pain relief than nonpenetrating sham acupuncture (SMD,
−.; % CI, −. to −.;RCTs),butnottheseof
penetrating sham acupuncture (SMD, −.; % CI, −.
to .; RCTs). Interestingly, when we excluded the study
by Zhang et al. [], we found real acupuncture was more
eective than the sham acupuncture in relieving pain imme-
diately aer acupuncture treatment, which indicates some
sham acupuncture treatment is not inactive.
Our systematic review and meta-analysis study focuses
on the immediate analgesic eect of acupuncture. is raises
some interesting questions. e rst question is whether the
immediately analgesic eect following the rst acupuncture
treatment can be used as a predictor for the success of sub-
sequent or long-term acupuncture treatment. Most clinical
trials focused on analgesic eects aer multiple acupuncture
treatment. Few studies assessed analgesic eects aer both
immediate posttreatment and multiple acupuncture treat-
ments. erefore, further studies must be performed to clar-
ify this issue. e second question is whether the immediate
acupuncture analgesic eect and cumulative analgesic eects
following repeated acupuncture treatments share common
mechanisms. us far, there is no clear documentation in
regard to the underlying mechanisms of these two analgesic
eects. Based on the available data published, needle inser-
tion of the local acupuncture points triggers the release of
adenosine and changes of broblast organization at the loose
connective tissue layer [–]. e cumulative analgesic
eects following repeated acupuncture treatments on the
brain dier from the immediate analgesic eect aer one acu-
puncture treatment. e immediate analgesic eect of acu-
puncture was a result of an extensive brain activation at
selective pain-related regions []. However, the cumulative
analgesic eects of acupuncture indicated bimodal habitua-
tion—a positive brain response appeared at the beginning of
acupuncture stimulation, which then declined and became
negative towards the nal stages []. From neurohormonal
prospective, a single acupuncture treatment can facilitate
the release of opioid peptides []. Repeated administration
of electroacupuncture leads to the development of opioid
Evidence-Based Complementary and Alternative Medicine
tolerance [, ]. erefore, although acupuncture has
both immediate and cumulative analgesic eects following
repeated treatments, underlying mechanisms may be dier-
ent.
Our systematic review and meta-analysis study has sev-
eral limitations. Only English and Chinese literatures were
reviewed in present study and potential data from studies
published in other languages might exist and were ignored,
which decreased the credibility of the results in present study
to some extent. We included RCTs evaluating various types
of pain, including chronic neck pain, LBP, and knee pain.
In fact, accumulated work has shown that acupuncture is
benecial in treatment of various pain syndromes. e eects
of acupuncture on nonspecic pain may share the similar
underlying mechanisms. In traditional Chinese medicine,
disease-related pain results from stagnation of energy “Qi”
owwithinmeridians.Painistreatedlocallyordistally
via acupuncture points further along the meridian, drawing
energy away from the pain. Recently, the neurophysiology of
acupuncture has been investigated extensively. Local anesthe-
sia at the needle-insertion sites completely blocks the imme-
diate analgesic eect of acupuncture, indicating that these
eects are dependent on intact neural conduction. e imme-
diate analgesic eect on various types of pain may be involved
in the nociceptive pathway, including descending noradren-
ergic and serotonergic pathways []. In our meta-analysis, a
high level of heterogeneity may be resulted from the baseline
values, the acupuncture manipulation, acupuncture points
selected, and the duration and frequency of treatment. Our
review has a number of strengths. First, our search for
relevant studies was extensive. Key Chinese databases were
explored in addition to the English databases. Second, we
assessed the dierences in the immediate analgesic eect of
acupuncture between real acupuncture and dierent types of
controls. ird, the review only evaluated RCTs, which have
study designs appropriate for the determination of the eects
of intervention.
In conclusion, this review facilitates a better understand-
ing of acupuncture stimulation and its immediate analgesic
eect for disease-related pain. e results of our systematic
review and meta-analysis suggest that evidence of the imme-
diate analgesic eect of acupuncture is encouraging, but not
convincing. Nevertheless, our review has yielded interesting
andinnovativendingsandprovidedimpetustofurther
investigations. Further rigorous, high-quality, randomized
controlled trials comparing acupuncture with nontreatment
and sham acupuncture without skin penetration are required
to evaluate the immediate analgesic eect of acupuncture.
Conflicts of Interest
eauthorshavenoconictsofinteresttodeclare.
Authors’ Contributions
AnfengXiangandKeChengcontributedequallytothiswork.
Acknowledgments
e authors thank Dr. Lixing Lao at the School of Chinese
Medicine,UniversityofHongKong,Dr.BingZhuatChina
Academy of Chinese Medical Sciences, and Dr. Yih-Ing Hser
at the University of California, Los Angeles, for helpful
comments on the manuscript. is work was funded by the
National Basic Research Program of China ( Program:
CB) and the National Natural Science Foundation
of China (NSFC: ).
References
[] RelievingPaininAmerica:ABlueprintforTransformingPre-
vention, Care, Education, and Research, National Academies
Press, Washington, D.C., USA, , Institute of Medicine (US)
Committee on Advancing Pain Research, Care, and Education,
Institute of Medicine.
[]H.Breivik,B.Collett,V.Ventafridda,R.Cohen,andD.Gal-
lacher, “Survey of chronic pain in Europe: prevalence, impact
on daily life, and treatment,” EuropeanJournalofPain,vol.,
no. , pp. –, .
[] Q.Shi,G.Langer,J.Cohen,andC.S.Cleeland,“PeopleinPain:
How Do ey Seek Relief?” Journal of Pain,vol.,no.,pp.
–, .
[] A. Narayana, N. Katz, A. C. Shillington et al., “National
Breakthrough Pain Study: Prevalence, characteristics, and asso-
ciations withhealth outcomes,” Pain,vol.,no.,pp.–,
.
[]B.Sivertsen,T.Lallukka,K.J.Petrie,O.A.Steingrimsdottir,
A. Stubhaug, and C. S. Nielsen, “Sleep and pain sensitivity in
adults,” Pain,vol.,no.,pp.–,.
[] L. Jones, M. Othman, T. Dowswell et al., “Pain management for
women in labour: an overview of systematic reviews,” Cochrane
Database of Systematic Reviews, no. , Article ID CD,
.
[] H. Lee, J.-H. Lee, T.-Y. Choi, M. S. Lee, and B.-C. Shin, “Acu-
puncture for acute low back pain: a systematic review,” Clinical
Journal of Pain,vol.,no.,pp.–,.
[] C. A. Smith, X. Zhu, and L. He, “Acupuncture for primary dys-
menorrhea,” e Cochrane Database of Systematic Review,vol.
, no. , Article ID D, p. CD, .
[] A. J. Vickers, A. M. Cronin, A. C. Maschino et al., “Acupunc-
ture for chronic pain: individual patient data meta-analysis,”
Archives of Internal Medicine,vol.,no.,pp.–,
.
[] L. Casimiro, L. Barnsley, L. Brosseau et al., “Acupuncture and
electroacupuncture for the treatment of rheumatoid arthritis,”
e Cochrane Database of Systematic Review,vol.,no.,p.
CD, .
[] Y. D. Kwon, M. H. Pittler, and E. Ernst, “Acupuncture for peri-
pheral joint osteoarthritis: a systematic review and meta-
analysis,” Rheumatology,vol.,no.,pp.–,.
[] E. Manheimer, A. White, B. Berman, K. Forys, and E. Ernst,
“Meta-analysis: acupuncture for low back pain,” Annals of
Internal Medicine,vol.,no.,pp.–,.
[] H. Y. Chiu, Y. J. Hsieh, and P. S. Tsai, “Systematic review and
meta-analysis of acupuncture to reduce cancer-related pain,”
European Journal of Cancer Care,vol.,no.,ArticleID
e, .
[] C. H. Y. Lau, X. Wu, and V. C. H. Chung, “Acupuncture
and Related erapies for Symptom Management in Palliative
Cancer Care: systematic Review and Meta-Analysis,” Medicine
(Baltimore),vol.,no.,ArticleIDee,p.e,.
Evidence-Based Complementary and Alternative Medicine
[]Z.Lu,H.Dong,Q.Wang,andL.Xiong,“Perioperativeacu-
puncture modulation: More than anaesthesia,” British Journal
of Anaesthesia,vol.,no.,pp.–,.
[] M. H. Pittler and E. Ernst, “Complementary therapies for
neuropathic and neuralgic pain: Systematic review,” Clinical
Journal of Pain,vol.,no.,pp.–,.
[] J. Langhorst, P. Klose, F. Musial, D. Irnich, and W. H¨
auser,
“Ecacy of acupuncture in bromyalgia syndrome: a system-
atic review with a meta-analysis of controlled clinical trials,”
Rheumatology,vol.,no.,pp.–,.
[] E. Ernst, M. S. Lee, and T.-Y. Choi, “Acupuncture: does it
alleviate pain and are there serious risks? A review of reviews,”
Pain,vol.,no.,pp.–,.
[] J. S. Han, “Acupuncture: neuropeptide release produced by
electrical stimulation of dierent frequencies,” Tre nds in Neu-
rosciences,vol.,no.,pp.–,.
[] F. Beissner and C. Henke, “Methodological problems in fMRI
studies on acupuncture: a critical review with special emphasis
on visual and auditory cortex activations,” Evidence-Based
Complementary and Alternative Medicine, vol. , Article ID
, pages, .
[] S. Liu, W. Zhou, X. Ruan et al., “Activation of the hypothalamus
characterizes the response to acupuncture stimulation in heroin
addicts,” Neuroscience Letters,vol.,no.,pp.–,.
[] A. Margolin, S. K. Avants, and H. D. Kleber, “Investigating
alternative medicine therapies in randomized controlled trials,”
Journal of the American Medical Association, vol. , no. , pp.
–, .
[] K. J. Sherman, D. C. Cherkin, D. M. Eisenberg, J. Erro, A. Hrbek,
and R. A. Deyo, “e practice of acupuncture: Who are the
providers and what do they do?” Annals of Family Medicine,vol.
, no. , pp. –, .
[] H. MacPherson and R. Hammerschlag, “Acupuncture and the
Emerging Evidence Base: Contrived Controversy and Rational
Debate,” JAMS Journal of Acupuncture and Meridian Studies,
vol.,no.,pp.–,.
[] S.A.P.Calamita,D.A.Biasotto-Gonzalez,N.C.DeMeloetal.,
“Evaluation of the immediate eect of acupuncture on pain,
cervical range of motion and electromyographic activity of the
upper trapezius muscle in patients with nonspecic neck pain:
Study protocol for a randomized controlled trial,” Tr i als ,vol.,
no.,articleno.,.
[]A.O.Freire,G.C.M.Sugai,S.M.Togeiro,L.E.Mello,
and S. Tuk, “Immediate eect of acupuncture on the sleep
pattern of patients with obstructive sleep apnoea,” Acupuncture
in Medicine,vol.,no.,pp.–,.
[] S. Shukla, A. Torossian, J.-R. Duann, and A. Leung, “e anal-
gesic eect of electroac upuncture on acute thermal p ain percep-
tion—a central neural correlate study with fMRI,” Molecular
Pain,vol.,article,.
[] C. Li, J. Yang, K. Park et al., “Prolonged repeated acupuncture
stimulation induces habituation eects in pain-related brain
areas: an fMRI study,” PLoS ONE,vol.,no.,ArticleIDe,
.
[] C. Lefebvre, E. Manheimer, and J. Glanville, “Chapter : Search-
ing for studies,” in Cochrane Handbook for Systematic Reviews of
Interventions,J.P.T.HigginsandS.Green,Eds.,eCochrane
Collaboration, .
[] M. Chen and S. Li, “Clinical observation of the ecacy on renal
colic treated with electroacupuncture at the Xi-cle points of
kidney and bladder meridians as well as the relevant Front-mu
points,” World Journal of Acupuncture—Moxibustion,vol.,
no.,pp.–,.
[] M. Inoue, H. Kitakoji, N. Ishizaki et al., “Relief of low back
pain immediately aer acupuncture treatment: a randomised,
placebo controlled trial,” Acupuncture in Medicine,vol.,no.
, pp. –, .
[] M. Inoue, T. Hojo, M. Nakajima, H. Kitakoji, and M. Itoi, “Com-
parison of the eectiveness of acupuncture treatment and
local anaesthetic injection for low back pain: A randomised
controlled clinical trial,” Acupuncture in Medicine,vol.,no.
, pp. –, .
[] C.-Z. Liu, J.-P. Xie, L.-P. Wang et al., “A randomized controlled
trial of single point acupuncture in primary dysmenorrhea,”
Pain Medicine (United States),vol.,no.,pp.–,.
[] T.W.Lu,I.P.Wei,Y.H.Liuetal.,“Immediateeectsofacu-
puncture on gait patterns in patients with knee osteoarthritis,”
Chinese Medical Journal,vol.,no.,pp.–,.
[] M. J. Mejuto-V´
azquez, J. Salom-Moreno, R. Ortega-Santiago, S.
Truyols-Dom´
ınguez, and C. Fern´
andez-De-Las-pe˜
nas, “Short-
Term changes in neck pain, widespread pressure pain sensitiv-
ity, and cervical range of motion aer the application of trigger
point dry needling in patients with acute mechanical neck pain:
a randomized clinical trial,” JournalofOrthopaedicandSports
Physical erapy,vol.,no.,pp.–,.
[] Y. Maeda, N. Kettner, J. Lee et al., “Acupuncture-evoked res-
ponse in somatosensory and prefrontal cortices predicts imme-
diate pain reduction in carpal tunnel syndrome,” Evidence-
Based Complementary and Alternative Medicine,vol.,
Article ID , pages, .
[] T. Nabeta and K. Kawakita, “Relief of chronic neck and
shoulder pain by manual acupuncture to tender points - A
sham-controlled randomized trial,” Complementary erapies
in Medicine,vol.,no.,pp.–,.
[] J.-S. Shin, I.-H. Ha, J. Lee et al., “Eects of motion style acupunc-
ture treatment in acute low back pain patients with severe
disability: a multicenter, randomized, controlled, comparative
eectiveness trial,” Pain,vol.,no.,pp.–,.
[] R. S. M. Stival, P. R. Cavalheiro, C. E. S. Stasiak, D. T. Galdino,
B. E. Hoekstra, and M. D. Schafranski, “Acupuncture in bro-
myalgia: a randomized, controlled study addressing the imme-
diate pain response,” Revista Brasileira de Reumatologia,vol.,
no. , pp. –, .
[]J.-T.Su,Q.-H.Zhou,R.Li,J.Zhang,W.-H.Li,andQ.Wang,
“Immediate analgesic eect of wrist-ankle acupuncture for
acute lumbago: a randomized controlled trial,” Chinese Acu-
puncture & Moxibustion,vol.,no.,pp.–,.
[] S.-H. Yang, P.-C. Xie, and X.-L. Qin, “An instant pain-relief
eect of balance acupuncture for relieving sore throat in acute
pharyngitis patients,” Acupuncture Research,vol.,no.,pp.
–, .
[]H.Zhang,Y.Hu,J.Wu,andH.Zheng,“Timelinesslawon
the immediate analgesia on acute migraine treated with elec-
troacupuncture at shaoyang meridian points,” Chinese acupunc-
ture & moxibustion,vol.,no.,pp.–,.
[] J. P. T. Higgi ns, J. J. Deeks, and D. G. Altman, “Chapter :
Special topics in statistics,” in Cochrane Handbook for Systematic
Reviews of Inter ventions,J.P.T.HigginsandS.Green,Eds.,e
Cochrane Collaboration, , Version ...
[] J. P. T. Higgins and J. J. Deeks, “Chapter : Selecting stud-
ies and collecting data,” in Cochrane Handbook for System-
atic Reviews of Interventions,J.P.T.HigginsandS.Green,
Evidence-Based Complementary and Alternative Medicine
Eds., e Cochrane Collaboration, , Version .., http://
handbook--.cochrane.org/.
[] J. P. T. Higgins, D. G. Altman, and J. A. C. Sterne, “Chapter
: Assessing risk of bias in included studies,” in Cochrane
HandbookforSystematicReviewsofInterventions,J.P.T.Higgins
and S. Green, Eds., e Cochrane Collaboration, , Version
...
[] K. Streitberger and J. Kleinhenz, “Introducing a placebo needle
into acupuncture research,” e Lancet,vol.,no.,pp.
-, .
[] E. Manheimer, L. S. Wieland, K. Cheng et al., “Acupuncture for
irritable bowel syndrome: systematic review and meta-analysis,”
American Journal of Gastroenterology,vol.,no.,pp.–
, .
[] Review Manager, “e Nordic Cochrane Centre,” computer
program, Version ., e Cochrane Collaboration, Copen-
hagen, Denmark, .
[] J. P. T. Higgins, S. G. ompson, J. J. Deeks, and D. G. Altman,
“Measuring inconsistency in meta-analyses,” British Medical
Journal,vol.,no.,pp.–,.
[] J. J. Deeks, J. P. T. Higgins, and D. G. Altman, “Chapter :
Analysing data and undertaking meta-analyses,” in Cochrane
HandbookforSystematicReviewsofInterventions,J.P.T.Higgins
and S. Green, Eds., e Cochrane Collaboration, , Version
...
[] H. J. Sch¨
unemann, A. D. Oxman, and G. E. Vist, “Chapter
: Interpreting results and drawing conclusions,” in Cochrane
HandbookforSystematicReviewsofInterventions,J.P.T.Higgins
and S. Green, Eds., e Cochrane Collaboration, , Version
...
[] T. Jonsson, C. B. Christensen, H. Jordening, and C. Frølund,
“e bioavailability of rectally administered morphine Pharma-
cology and Toxicology,” Pharmacology & Toxicology,vol.,no.
, pp. –, .
[] M. J. Brennan, “e eect of opioid therapy on endocrine
function,” American Journal of Medicine, vol. , no. , pp. S–
S, .
[] Beijing College of Traditional Chinese Medicine, Shanghai Col-
lege of Traditional Chinese Medicine, Nanjing College of Tradi-
tional Chinese Medicine, and e Acupuncture Institute of
the Academy of Traditional Chinese Medicine, “Essentials of
Chinese aBeijing,” , Beijing, People’s Republic of China,
Foreign Language Press; Beijing, People’s Republic of China,
.
[] L. Liu, Q.-M. Huang, Q.-G. Liu et al., “Eectiveness of dry
needling for myofascial trigger points associated with neck and
shoulderpain:asystematicreviewandmeta-analysis,”Archives
of Physical Medicine and Rehabilitation,vol.,no.,pp.–
, .
[] D. C. Cherkin, K. J. Sherman, A. L. Avins et al., “A randomized
trial comparing acupuncture, simulated acupuncture, and usual
care for chronic low back pain,” Archives of Internal Medicine,
vol. , no. , pp. –, .
[] M.V.Madsen,P.C.Gøtzsche,andA.Hr
´
objartsson, “Acupunc-
ture treatment for pain: systematic review of randomised
clinical trials with acupuncture, placebo acupuncture, and no
acupuncture groups,” British Medical Journal,vol.,no.,
pp. –, .
[] M. E. Suarez-Almazor, C. Looney, and Y. Liu, “A randomized
controlled trial of acupuncture for asteoarthritis of the knee:
eects of patient-provider communication,” Arthritis Care and
Res (Hoboken),vol.,no.,pp.–,.
[] H. M. Langevin, “Evidence of connective tissue involvement
in acupuncture,” e FASEB Journal: Ocial Journal of the
Federation of American Societies for Experimental Biology,vol.
, no. , pp. –, .
[] N. Goldman, M. Chen, T. Fujita et al., “Adenosine A receptors
mediate local anti-nociceptive eects of acupuncture,” Nature
Neuroscience, vol. , no. , pp. –, .
[] M.Sandberg,T.Lundeberg,L.Lindberg,andB.Gerdle,“Eects
of acupuncture on skin and muscle blood ow in healthy
subjects,” European Journal of Applied Physiology,vol.,no.
-,pp.–,.
[] R. P. Dhond, N. Kettner, and V. Napadow, “Neuroimaging
acupuncture eects in the human brain,” Journal of Alternative
and Complementary Medicine,v
ol.,no.,pp.–,.
[] H. Ji-Sheng, L. Si-Jia, and T. Jian, “Tolerance to electroacupunc-
ture and its cross tolerance to morphine,” Neuropharmacology,
vol. , no. , pp. –, .
[] P. Chandran and K. A. Sluka, “Development of opioid toler-
ance with repeated transcutaneous electrical nerve stimulation
administration,” Pain,vol.,no.-,pp.–,.
[] Z.-Q. Zhao, “Neural mechanism underlying acupuncture anal-
gesia,” Progress in Neurobiology, vol. , no. , pp. –, .
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