Clinical Rehabilitation 2016 (Feb); 30 (2): 145-155 ~ FULL TEXT
Liguo Zhu, Xu Wei and Shangquan Wang
Department of Spine,
Beijing, People's Republic of China.
OBJECTIVE: To access the effectiveness and safety of cervical spine manipulation for cervical radiculopathy.
DATA SOURCES: PubMed, the Cochrane Central Registry of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang data, the website of Chinese clinical trial registry and international clinical trial registry by US National Institutes of Health.
REVIEW METHODS: Randomized controlled trials that investigated the effects of cervical manipulation compared with no treatment, placebo or conventional therapies on pain measurement in patients with degenerative cervical radiculopathy were searched. Two authors independently evaluated the quality of the trials according to the risk of bias assessment provided by the PEDro (physiotherapy evidence database) scale. RevMan V.5.2.0 software was employed for data analysis. The GRADE approach was used to evaluate the overall quality of the evidence.
RESULTS: Three trials with 502 participants were included. Meta-analysis suggested that cervical spine manipulation (mean difference 1.28, 95% confidence interval 0.80 to 1.75; P < 0.00001; heterogeneity: Chi2 = 8.57, P = 0.01, I2 = 77%) improving visual analogue scale for pain showed superior immediate effects compared with cervical computer traction. The overall strength of evidence was judged to be moderate quality. One out of three trials reported the adverse events and none with a small sample size.
CONCLUSION: There was moderate level evidence to support the immediate effectiveness of cervical spine manipulation in treating people with cervical radiculopathy. The safety of cervical manipulation cannot be taken as an exact conclusion so far.
From the Full-Text Article:
Degenerative cervical radiculopathy is a frequent
impairment owing to compression of a cervical
nerve root, a term used to describe neck pain associated
with pain radiating into the arm (cervicobrachial
pain). [1, 2] As the best known type of
cervical spondylosis, cervical radiculopathy is
often induced by osteophytosis, cervical interverbral
disc herniation. In China, the prevalence of
cervical spondylosis was 17.3%, and a high percentage
of 60% to 70% of patients were occupied
by cervical radiculopathy. [3, 4]
Treatment of cervical radiculopathy is often
managed through conservative therapies, which
includes oral analgesics, oral steroids, cervical
computer traction, manual therapy, exercise, cervical
collar and various combinations of these. [5, 6] But
treatments are subject to some limitations owing to
the quality of evidence and adverse drug reaction.
In a comprehensive literature synthesis conducted
by Task Force on Neck Pain and its Associated
Disorders, the insufficient study evidence of noninvasive
interventions for patients with radicular
symptoms was available.  Oral non-steroidal antiinflammatory
drugs are generally used to alleviate
severe pain. On the other hand, long-term nonsteroidal
anti-inflammatory drugs use may increase
the risk and cause gastrointestinal ulcers, serious
cardiovascular events, hypertension, acute renal
failure and worsening of pre-existing heart failure. 
In the world, many patients with cervical radiculopathy
are increasingly turning to specific conservative
treatments, including cervical spine
manipulation, to relieve their symptoms and reduce
the side-effects of medications.
[9–11] The action
effects of cervical manipulative therapy have been
found or validated in some experiments, such as
separation of the facet joints, relaxation of paraspinal
muscles, increasing of blood flow and so on. 
As one of the complementary and alternative
therapies, cervical spine manipulation has been
used for several years in China. [13, 14] According to
the definition provided in the literatures, cervical
manipulation is described as the use of hands
applied to the patients, thereafter a rapid highvelocity,
low-amplitude thrust directed at the cervical
joints, often accompanied by an audible
crack. [15, 16] Additionally, light soft-tissue massage,
which is used to facilitate treatment, is permitted
before manipulation.  Cavitation should not be
considered as an absolute indicator for successful
thrust manipulation. [18, 19]
Recently, recommendation was made for the
treatment of non-specific neck pain with spinal
manipulation in a new evidence-based guideline. 
However, there is relatively little evidence
into the effectiveness and safety of cervical spine
manipulation for specific neck pain, including
cervical radiculopathy. The following questions
(1) the effectiveness of standalone
intervention, cervical manipulation for neck
pain with radiculopathy;
(2) the adverse effect of
To date, although a number
of systematic reviews included cervical spine
manipulation for cervical radiculopathy, the
reviews did not report results for cervical radiculopathy
[21–27] Therefore, the purpose of
this systematic review is to evaluate the literature
regarding the effectiveness and safety of using
cervical spine manipulation in the treatment of
Inclusion criteria and exclusion criteria
All the parallel randomized controlled trials that
compared cervical manipulation to no treatment
or conventional therapy in patients with cervical
radiculopathy were included. According to the
definition of the North American Spine Society,
cervical radiculopathy was defined as neck pain
in a radicular pattern in one or both upper extremities
related to compression and/or irritation of
one or more cervical nerve roots.  Cervical spine
manipulation referred to a “manual therapy technique
comprising a continuum of skilled passive
movements to the cervical joints and/or related
soft tissues that are applied at varying speeds and
amplitudes, including a small-amplitude/highvelocity
therapeutic movement”.  In addition,
randomized controlled trials that compared cervical
manipulative therapy and existing conventional
therapies with conventional therapies for
cervical radiculopathy were included as well. The
outcome measurement was validated with the visual
analogue scale, numerical rating scales,
McGill pain questionnaire on pain relief or analogous
There were no restrictions on population characteristics
and publication type. Languages of published
or unpublished literatures were restricted in
English and Chinese. Quasi-randomized controlled
trials were not enrolled. Duplicated publications
reporting the same groups of populations were
excluded. Abstract for which full reports were not
available and letters to the editor were also excluded.
Database and search strategies
The following literature sources were searched up to
December 2014: PubMed (1966–2014), the
Cochrane Central Registry of Controlled Trials
(CENTRAL) in the Cochrane Library (Issue 12
of 12, December 2014), EMBASE (1980–2014),
Chinese Biomedical Literature Database (CBM)
(1978–2014), Chinese National Knowledge Infrastructure
(CNKI) (1989–2014), Chinese Scientific
Journal Database (VIP) (1989–2014) and Wanfang
data (1989–2014). All searches were completed on
25 December 2014. Registered clinical trials were
conducted in the website of Chinese clinical trial
registry (http://www.chictr.org) and international
clinical trial registry by US National Institutes of
Health (http://clinicaltrials.gov). The search terms
and their combination were used: “radiculopathy”,
“cervical radiculopathy”, “cervicobrachial pain”,
“cervical spondylotic radiculopathy”, “cervical disc
herniation”, “conservative treatment”, “conservative
therapy”, “manual therapy”, “cervical spine
manipulation”, “manipulati*”, “random”, “review”.
Eligible studies were selected and checked independently
by two authors (XW and SW).
Data extraction and methodological
Two authors (XW and SW) conducted data extraction
independently according to predefined criteria.
The extracted data included the author names, year
of publication, sample size, mean age and symptom
duration, diagnosis criteria, type of manipulation,
treatment process, details of the intervention and
control, duration of the treatment and follow-up,
outcome measurement and adverse effects for each
study. Disagreement was resolved by discussion
and reached consensus through a third party (LZ). If
additional data was needed, we contacted the study
authors in time.
The methodological quality of included randomized
controlled trials was assessed independently
using criteria from the PEDro (physiotherapy
evidence database) scale (XW and SW).  The 11
items were evaluated in the PEDro scale. Each
item was answered either “no” or “yes”. If a criterion
was satisfied, a point would be awarded for
that criterion, a zero otherwise. Owing to the eligibility
criterion item not being included in the total
score, the maximum value of the PEDro scale was
10. To determine an accepted cut-off point for this
review, two systematic reviews by Maher  and
Boyles et al.  were consulted. The PEDro scale
total score of 5 was considered to be acceptable as
the cut-off point, which indicated a low risk of
Dichotomous data were expressed as relative risk
(RR) and continuous outcomes as mean difference
(MD), both with 95% confidence interval (CI). The
mean difference value between the end of the final
intervention and the baseline was used to assess the
difference between the groups. Heterogeneity was
assessed using both the Chi-squared test and the I2
statistic with an I2 value greater than 50% indicative
of substantial heterogeneity. We used Revman
5.2.0 software provided by Cochrane Collaboration
for data analysis. 
Strength of evidence
We applied the GRADE (Grades of Recommendation,
Assessment, Development, and Evaluation)
approach to evaluate the overall quality of the evidence. 
Five basic factors could decrease the quality
(1) Limitations in study design and/or execution;
(2) inconsistency of results;
(3) indirectness of evidence;
(4) imprecision of results;
(5) publication bias.
There were also three factors for
upgrading.  Two independent reviewers (XW and
SW) assessed the quality of evidence. The quality of
the evidence was downgraded by one level when
one of the factors described above was met. The following
grading of quality of evidence and definitions
High quality: Further research is very unlikely
to change our confidence in the estimate of
Moderate quality: Further research is likely to
have an important impact on our confidence in
the estimate of effect and may change the
Low quality: Further research is very likely to
have an important impact on our confidence in
the estimate of effect and is likely to change
Very low quality: Any estimate of effect is
Description of included trials
A flowchart depicted the literature search process
and clinical study selection (Figure 1 gives details
of the included and excluded studies). A total of
2518 articles were identified by the initial search.
After 1,502 duplicates were removed, 1,016 articles
were screened. After reading the titles and abstracts,
968 articles of them were excluded. Full texts of 48
articles were retrieved, and finally three randomized
controlled trials were included.
[35–37] All the
studies were published in Chinese.
PRISMA 2009 flow diagram.
The characteristics of the included trials are
summarized in Table 1. The number of patients with
degenerative cervical radiculopathy was 502. There
was a wide variation in the average age of each
group (45–53.6years). Two different diagnostic criteria
of cervical radiculopathy were used in the
included studies: Two trials adopted the Summary
of diagnostic criteria in the second special forum of
cervical spondylosis organized by the Chinese
Medical Association in 1993. [35, 36, 38] Another trial
reported Diagnostic and therapeutic effect criteria
for diseases and syndromes in traditional Chinese
medicine issued by State Administration of traditional
Chinese medicine in 1994. [37, 39] Two diagnostic
criteria were almost the same for the main
symptoms and signs, imaging examination.
All of the trials had two arms. The interventions
included three types of manipulation in the fields,
and the controls only comprised cervical traction.
(The different manipulative therapies are presented
later in Table 3.) The treatment duration ranged
from two to four weeks. Only one trial related to
one month follow-up.  One trial described an
adverse event.  All the visual analogue scale
(VAS) scores were on neck and aim pain; the most
severe pain intensity was recorded.
Methodological quality of included trials
As shown in Table 2, methodological quality scores
of the included studies ranged from 5 to 6 points
according to the PEDro scale. The PEDro scale
predetermined score cut-off 5 was met or exceeded
by all the studies included, but two in three trials
just reached the limit of the cut-off score. Items 2,
4, 8, 10, 11 (random allocation, similar at baseline,
less than 15% drop-out, between-group statistical
comparisons, point measures and measures of variability)
all counted a point on each article. However,
items 5–7, 9 (subjects, therapists, assessors blinded,
intention-to-treat analysis) scored a zero for all the
studies. In the clinical studies of spine manipulation,
blindness implementation was difficult for
patients and therapists, even impossible to design. 
As for the assessors being blinded, no details were
found in all three articles. In addition, only one trial
mentioned the allocation concealment. 
Characteristics of RCTs of cervical spine manipulation in the treatment of cervical radiculopathy.
PEDro scale of quality for included randomized controlled trials.
Effect of the interventions
Only one meta-analysis was conducted with a forest
plot as shown in Figure 2. All the control groups
of included trials used cervical computer traction.
Three trials compared cervical spine manipulation
alone with cervical computer traction. Of these, all
trials compared cervical rotational manipulation
vs. cervical computer traction (20 minutes daily),
cervical rotation–traction manipulation vs. cervical
computer traction (30 minutes daily), cervical fixpoint
traction manipulation vs. cervical computer
traction (30 minutes daily), respectively. A significant
difference was found in the VAS in all three
trials (Table 3).
[34–36] This meta-analysis was made
on the VAS-change scores.
Forest plot of comparison: Cervical spine manipulation vs. cervical computer traction.
CI: confidence interval
IV: inverse variance.
Summary of the included studies in the review.
Our research used a random effect model. The
result indicated a high heterogeneity among the
studies (Chi2=8.57, P=0.01, I2=77%; three trials).
Meta-analysis suggested that cervical spine manipulation
showed superior immediate effects compared
with cervical computer traction in improving
VAS for pain (n=502; MD: 1.28, 95% CI: 0.80 to
The overall level of evidence was judged to be
moderate quality. The main reasons for downgrading
were limitations in inconsistency
of results (downgraded when there was statistical
heterogeneity (I2 > 50%)). No studies were
Only one trial reported the adverse events and
none were observed in the trial with a small sample
size.  The other two trials did not mention
whether adverse events have occurred in the intervention
or control group. Because of the limited
number of trials (less than 10), additional analysis
of sensitivity, subgroup and publication bias could
not be conducted.
Summary of the evidence
Cervical spine manipulation has played an important
role in the development of traditional Chinese
medicine over the last decade in China.  At the
same time cervical manipulation has been accepted
and favored by clinicians, chiropractors and physiotherapists
around the world. Neck pain is the most
common symptom of cervical radiculopathy, having
an impact on cervical vertebra range of motion
and function. In our systematic review, moderatelevel
evidence from three trials suggested that cervical
spine manipulation appears to be beneficial,
providing immediate effect on pain relief in patients
with degenerative cervical radiculopathy. Cervical
computer traction is the single active control therapy
in the included studies.
Comparison with the literature
So far, eight intervention systematic reviews about
the non-invasive treatment for cervical radiculopathy
could be retrieved in the seven electric databases.
However, each systematic review
included a variety of conservative intervention or
complex intervention. Few studies related to the
sole cervical rotational manipulation, thus making
it difficult to isolate the therapeutic effect of cervical
manipulation as a stand-alone intervention.
Besides that, two systematic reviews were qualitative
analysis and Chinese randomized controlled
trials were not contained in all articles.
Another previous systematic review by Lin
et al.  was about Chinese manipulation on mechanic
neck pain. The authors included different types
of cervical spondylosis, whereas we only paid
attention to cervical radiculopathy. On the other
hand, in our review, outcome measurement tools
had been validated and used by many other studies.
But in the study by Lin et al., the outcome assessment
system for cervical spondylosis radiculopathy
(OASCSR) had not been peer-reviewed by
experts outside China.
Strengths and limitations
Up to present, there was no systematic review of
randomized controlled trials on treatment by cervical
manipulation and measurement with the pain
scores in the field of cervical radiculopathy. This is
the first systematic review on the effectiveness and
safety of cervical spine manipulation aimed at
patients with cervical radiculopathy. Nonetheless,
there are still some limitations in the review.
First of all, the methodological quality of primary
studies played an important role in each of reviews.
The PEDro scale, often used to evaluate physiotherapy
evidence, was applied to assess the quality of
included randomized controlled trials in this review. 
All the trials described randomization procedures,
but two out of three trials reported the specific methods
including central randomization and computer
[36–37] Only one trial has not stated the random
allocation with detailed information.  At the
same time, strict implementation of random sequence
must be secured through allocation concealment. In
the review, two trials failed to mention the concealed
allocation in details. [35, 37] All articles clearly pointed
out withdraw or drop-out, but three articles did not
use intention-to-treat analysis. In these articles, the
authors did not report drop-out cases in the final analysis.
None of trials had a pretrial estimation of sample
size. The treatment duration of included trials
was short, varying from two to four weeks, and only
one trial designed a one-month follow-up.  There
was no comparison between manipulation and no
treatment, placebo or other therapies (except cervical
traction) in the eligible studies.
Moreover, there was lack of adverse event
reports for the included studies. One out of three
trials mentioned the safety of cervical manipulation
and none was observed in the study.  In other studies,
there was simply no mention of adverse events
whatsoever. Owing to the limited information, we
could not arrive at the conclusion on the safety of
cervical spine manipulation. Therefore, the record
of adverse events should be added in study design
and reported according to the Consolidated
Standards of Reporting Trials (CONSORT) statement
extension on harms reporting guidelines in the
future studies of manipulative therapy. Yet despite
all that, a causal relationship between treatment and
the potential serious adverse event and such relation
was really difficult to establish. The limited high
quality research that, to our best knowledge, is
available on adverse events in relation to manipulation
did not suggest a causal pathway.
Last but not the least, all of the studies screened
after completing the searches were published in
Chinese. Regrettably, all randomized controlled
trials have not yet completed registration through
there international clinical trials registry platform.
There was still a risk that we missed relevant studies
by not including other search terms, such as
underlying pathogeneses resulting in cervical
radiculopathy. Retrieval languages of literatures
were restricted in English and Chinese. Some other
languages published literatures could not be completely
searched. Therefore, it is not clear whether
potential publication bias could be eliminated fully.
Above all, cervical spine manipulation showed
significant immediate effects in improving pain
scores compared with cervical computer traction.
Long-term effects of cervical rotational manipulation
were not observed. The safety of cervical rotational
manipulation for degenerative cervical
radiculopathy cannot be taken as an exact conclusion.
Overall, there was moderate-level evidence
of cervical rotational manipulation for cervical
radiculopathy. More strict clinical controlled trials
are needed to generate a high level of evidence.
There was evidence from three trials of moderate quality that supported
spine manipulation in treating people
The adverse event of cervical spine
manipulation in treating degenerative
radiculopathy was not clear.
Conflict of interest
All authors declare that they have no conflict of
This work was partially supported by the National Science
and Technology Program of China [no. 2006BAI04A09
and no. 2014BAI08B06] and the Science and Technology
Program of China Academy of Chinese Medical Sciences
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