Pain Physician. 2019 (Mar); 22 (2): E55–E70 ~ FULL TEXT
Ian D. Coulter, PhD, Cindy Crawford, BA, Howard Vernon, DC, PhD, Eric L. Hurwitz, DC, PhD,
Raheleh Khorsan, PhD, Marika Suttorp Booth, MS,
and Patricia M. Herman, ND, PhD
Santa Monica, CA
BACKGROUND: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies.
OBJECTIVES: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain.
STUDY DESIGN: A systematic literature review and meta-analysis.
METHODS: We identified studies published between January 2000 and September 2017, by searching multiple electronic databases, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham, no treatment, each other, and other active therapies, or when combined as multimodal therapeutic approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria. When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation was applied to determine the confidence in effect estimates. This project was funded by the National Center for Complementary and Integrative Health under award number U19AT007912 and ultimately used to inform an appropriateness panel.
RESULTS: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred.
LIMITATIONS: The current evidence is heterogeneous, and sample sizes are generally small.
CONCLUSIONS: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain.
KEY WORDS: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic review, meta-analysis, appropriateness.
From the FULL TEXT Article:
An estimated 66% of the population will
suffer from neck pain at some point during
their lifetime.  In 2007, neck pain was
the second most common reason cited by patients for
using complementary and integrative medicine (CIM),
preceded only by low back pain.  The vast majority
of neck pain is not due to organic pathology, and
thus, has been termed “nonspecific” or “mechanical.”
Nonspecific neck pain is responsible for a significant
proportion of direct health care costs, visits to health
care providers, sick leave, and the related loss of
productivity. [3–5] Most nonspecific neck pain is not
associated with major disease or with neurologic signs
of nerve compression. For some patients, nonspecific
neck pain rarely, if at all, interferes with daily activities;
for others, nonspecific neck pain constitutes a major
hindrance to daily functioning.  More than one-third
of people affected still have low grade symptoms or
recurrences more than one year after treatment, often
leading to chronic pain). 
Many interventions are available for managing
nonspecific chronic neck pain, including analgesics as
prescribed by medical practitioners, physiotherapy,
educational modalities, exercise, and manual therapy. [4, 6, 8–10] Self-care management and educational modalities are usually the initial forms of treatment
for nonspecific chronic neck pain. There is some evidence
that educational videos are useful for patients
with whiplash-related neck pain.  There is little
evidence that these types of modalities are more effective
compared to other conservative therapies. [6, 12]
Physiotherapy, exercise, and manual therapies such as
massage, chiropractic, occupational, and osteopathic
therapies, including spinal manipulation and mobilization,
are used in isolation and in conjunction with other
therapies to treat nonspecific neck pain.
There are several systematic reviews of manual
therapies, such as spinal manipulation and mobilization,
for the treatment of neck pain. [5, 8, 13, 14] Some
reviews have found that there is no evidence or insufficient
evidence that spinal manipulative therapy is
superior to other standard treatments for patients with
chronic neck pain.  However, more recent systematic
reviews on chronic neck pain, as well as chronic low
back pain, suggest spinal manipulation and mobilization
are “viable” options for treating pain and reducing
disability.  The Bone and Joint Decade 2000–2010
Task Force  found that mobilization or exercise
sessions alone, or in combination with medications, are
the most beneficial treatment for short term neck pain. Others have concluded that interventions commonly
used by manual therapy practitioners, such as chiropractic
care, improve outcomes for the treatment of chronic
neck pain. [16, 17] The greatest increase in benefits has
been suggested for multimodal approaches, in which
multiple approaches are used together to treat chronic
neck pain. 
The long-term benefit of manual therapy is not
well established in the literature. A systematic review
of selected CIM therapies for neck and low back pain by
Furlan et al , comparing CIM therapies to other active
treatments (e.g., other CIM therapy, physiotherapy,
pain medication, usual care) found that, “manipulation
and mobilization effectiveness is variable depending
on symptom duration, outcome, comparator, whether
there is exercise or general practitioner care, and followup
period. Although this variability can be considered
inconsistent findings, the overall evidence suggests that
manipulation and mobilization are an effective treatment
modality compared to other therapies”.  The
findings of this systematic review regarding the effects
of manipulation on neck pain appear to be consistent
with both older and newer reviews. [8, 14]
The purpose of this systematic review was to evaluate
the randomized controlled trials (RCTs) published
from January 2000 through September 2017 on chronic
nonspecific neck pain, comparing the effects of manipulation
and/or mobilization as therapies to those of
other active therapies (such as acupuncture, massage
therapy, exercise, etc.) to sham or no treatment, and
when combined with other therapies such as exercise
or advice commonly seen in practice. The decision to
begin with January 2000 was based on the fact that
previous systematic reviews (SRs) existed up until that
date and this represented a more rational use of our resources.
The goal was to not only update the evidence
base since these previous reviews reported earlier, but
to better understand the effectiveness of the various
types of manipulation and/or mobilization for treating
chronic nonspecific neck pain, and the potential impact
on patient-reported outcomes associated with pain,
disability, and health-related quality of life (HRQoL).
When there were subsets of data the authors felt were
similar enough to pool, meta-analyses were attempted.
This review was in support of a larger project investigating
the appropriateness of manipulation/mobilization
for the treatment of chronic low back pain and
neck pain, funded by the National Center for Complementary
and Integrative Health under award number
The systematic review was done to present to a panel of experts who were making judgments
about the appropriateness of using manipulation and/
or mobilization for the treatment of nonspecific chronic
neck pain under different clinical scenarios. This grant
was a cooperative agreement and National Institutes of
Health (NIH) also appointed an external advisory committee
(EAC), who had the authority both to vote go/
no go with regard to the planned systematic review and
again to vote go/no go after reviewing the systematic
review itself. The systematic review was then presented
to an expert panel to use in their rating of the appropriateness
of manipulation and/or mobilization for
nonspecific chronic neck pain.
This systematic review and meta-analysis report
adhere to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines.
Search Strategy and Data Sources
This systematic review builds on previous systematic
reviews (up through 2000) that reported the evidence
base for manipulation and mobilization for neck pain. [8, 15, 19, 20] We searched PubMed/MEDLINE, Cochrane,
Embase, Cinahl, PsycInfo, and Index to Chiropractic
Literature (ICL) for studies published between January
2000 and September 2017. In addition, we searched reference
lists and consulted with subject matter experts.
The search strategy was intentionally designed to be
broad in nature without predefining the specific population
(i.e., not using the words ‘chronic’ or ‘nonspecific’)
or intervention (i.e., spanning multiple professions). In
addition, there were no limitations placed on control/
comparators, specific outcomes, or study designs, so
that the breadth and variations across the research
could be discovered, and the literature could inform
the appropriate definitions and subgroups to consider
for analysis. Because the NIH-funded project focused on
both chronic nonspecific neck pain and chronic low back
pain, we conducted the search to meet both needs. (Fig.
1 and Table 1)
A scoping review of the literature informed the definitions
and categorization of studies for systematic review.
We categorized studies accordingly to the specific
populations, interventions, control/comparators, patient
reported outcomes, and study designs discovered in the
literature base. We excluded studies clearly not related
to neck pain or to an intervention involving mobilization
and/or manipulation. We presented findings to an internal
steering committee (ISC) as well as an EAC. With the
help of these committees, evidence-informed definitions
and specific eligibility criteria were devised based on the
evidence base to be used in carrying out the systematic
review and attempted meta-analysis (Table 1).
Six reviewers used study eligibility criteria to independently
screen the literature in duplicate (Table 1).
Disagreements about inclusion were resolved through
discussion and consensus, or ultimately by the ISC.
Eligibility criteria included:
1) a population experiencing chronic [21, 22] and nonspecific  neck pain;
2) an intervention, with the involvement of a therapist, consisting of either
(i) manipulation (labeled as thrust),
(ii) mobilization (labeled as nonthrust), or
(iii) a multimodal integrative practice including manipulation
and/or mobilization components as part of the approach, labeled as a “program” if the observed effect
could not be attributed directly to the unimodal thrust
or nonthrust intervention (e.g., a study of chiropractic
plus acupuncture vs. usual care would be multimodal
and labeled as a “program” because chiropractic would
serve as an adjunctive therapy to acupuncture, separate
from chiropractic plus exercise vs. exercise in which the
observed effect could be attributed to the addition of
3) compared to sham, no treatment or any
other active therapies, such as exercise, physiotherapy,
or physical therapy; and
4) at least one outcome measuring
a reduction in pain intensity/severity. Although
all study designs were captured for the scoping of the
literature, only RCTs involving adult human subjects
(aged ≥ 18 years) were considered for this systematic
review and meta-analysis (Table 1).
For simplicity and because eligible studies included
many types and styles of therapies, the authors chose
to refer to the manipulation therapies as “thrust” and
mobilization therapies as “nonthrust.” The studies describing
programs and in which the effects could not
be attributed to thrust or nonthrust alone (multimodal
studies) were separated from those studies in which
the effect could be attributed to thrust or nonthrust
(unimodal studies) for the remainder of the systematic
review methods and to describe the quality of the evidence
for included studies.
Quality Assessment and Data Extraction
Risk of bias was assessed independently by 6 reviewers
in duplicate using the Scottish Intercollegiate
Guidelines Network (SIGN 50) checklist for RCTs (24).
We assessed external and model validity using the
External Validity Assessment Tool (EVAT) (25), which
measures the generalizability of research to other
individuals (external validity) and settings (model
validity) outside a study’s confines. We extracted data
to describe each included study, including the population,
intervention, control/comparators, and outcomes
at specific timepoints and across various prescribed
doses of treatment.
Data Synthesis and Analysis
Studies were grouped and labeled according to:
1) duration of chronic pain (i.e., at least 3 months, 6 months,
and 12 months); and
2) studies considered unimodal
with intervention arms consisting of thrust or nonthrust
compared to a sham, no treatment, another active intervention,
or a head-to head comparison, or separately,
when combined as a multimodal approach. This grouping
exercise allowed for the comparison of interventions.
It was also an attempt to reduce heterogeneity.
We extracted data from studies when available for
sample size, and mean and standard deviation for each
treatment group in pain intensity, disability, and HRQoL
outcomes at each timepoint: closest to one month, 3
months, and 6 months. We computed an unbiased
estimate using the Hedges’ effect size  and 95%
lower and upper limits, regardless of whether a study
was eligible for meta-analysis for all studies categorized
as unimodal (Appendix Table 1). A negative effect size
indicated a reduction in pain intensity or disability, and
favored manipulation or mobilization. For HRQoL, a
positive effect size indicated an increase in HRQoL with
treatment at those timepoints and favored manipulation
A minimum of 3 studies with sufficient homogeneity
was considered for meta-analysis. Single treatment
studies (one dose over one day), as well as multimodal
interventions in which the effects of manipulation/
mobilization could not be distinguished from the total
program, were excluded from any attempted pooling
for meta-analysis. For subsets in which authors felt studies
were similar enough to pool and data were available,
standardized mean differences (SMD) were computed
using Comprehensive Meta-Analysis software, Version
3.3.070 (CMA; Biostat, Englewood, NJ). Meta-analyses
of SMD were performed with the generic inverse model
of REVMAN (The Nordic Cochrane Centre for The Cochrane
Collaboration, Copenhagen, Denmark). We used
random effects models; statistical heterogeneity was
examined by I2 with low, moderate, and high I2 values
of 25%, 50%, and 75%, respectively.
We assessed publication
bias using the Begg adjusted rank correlation
test  and the Egger regression asymmetry test. 
Pooled effect sizes for pain and disability outcomes were
translated into the visual analog scale (VAS, 0–100) using
a standard deviation of 25 points, and the neck disability
index (NDI, 0–50) using a standard deviation of 12.5
points, respectively for clinical interpretation. [29, 30] For
constructing forest plots, a negative effect size indicated
a reduction in pain intensity or disability and favored
manipulation or mobilization; therefore, the thrust is
on the left side (–) column and active on the right. For
HRQoL, a positive effect size indicated an increase in
HRQoL with treatment at those timepoints and favored
manipulation or mobilization. Therefore, the effect is on
the right side for this outcome (+).
Regardless of whether studies were included in the
meta-analysis or not, we followed the Grading of Recommendations, Assessment, Development, and Evaluation
approach, to determine our confidence in the effects
reported and overall quality of the literature. 
Our search of multiple databases for studies of
both low back and neck pain yielded 7,460 records (Fig.
2). The systematic review for chronic low back pain has
already been published.  We report here only on the
47 unique randomized trials (53 publications total) eligible
for evaluation related to chronic nonspecific neck
pain. Of these, 37 unique trials (42 publications) [33–74]
were identified as unimodal in which the effect of manipulation
and/or mobilization could be distinguished
from that of the comparator. Ten trials (11 publications) [75–85] were multimodal studies that were designed more as “programs.” All the studies were included in
the qualitative analysis.
Characteristics of included studies are detailed in
Appendix Tables 1 and 2. The 47 included trials examining
either a uni- or multimodal intervention of thrust
and/or nonthrust for patients with chronic nonspecific
neck pain were published between January 2000 and
September 2015. No studies meeting the eligibility criteria
were found between January 2016 and September
2017. The total number of patients across the 47 trials
was 4,460, ranging from 16 in the smallest to 409
in the largest study. The average age of the patients
was approximately 40 years, ranging from ages 19–65
years. The studies included more men than women. For
unimodal and multimodal studies separately, average
duration of chronic pain ranged from 3 months or more
in 63% and 40% studies, > 6 months in 5% and 20%,
and greater than one year in 32% and 40% of included
Of the 37 unimodal studies, 46% were identified
as thrust interventions, 31% as nonthrust interventions,
19% included both thrust and nonthrust intervention
arms, and 4% used a combination of both thrust and
nonthrust as the intervention. The multimodal studies
included combination therapies, such as chiropractic
care, manual and physical therapy combined with
commonly prescribed exercises, massage, ultrasound,
education, or advice in which the effect of the thrust
or nonthrust could not be distinguished from that of
the program. The treatment period of studies was not
consistent and ranged from one day to across 4 months
with as few as a single treatment to up to 20 treatments
over 12 weeks (Appendix Tables 1 and 2).
Studies reported outcomes related to pain intensity/
severity, disability, and HRQoL. The most common
outcome measures used were the pain intensity VAS,
the NDI, and the Short Form-36 (SF-36) (Appendix
Tables 1 and 2).
According to the SIGN 50 criteria used to assess the
risk of bias, 18 of the 37 unimodal studies were judged
to be of high quality (++), 16 of acceptable quality
(+), and 3 of low quality (0) (Appendix Table 1). The
number of studies that were judged either well covered
or adequately addressed for SIGN 50 criteria included
baseline similarities between groups (36/37) at the start
of the trial, relevant outcomes measured using valid
and reliable methods (35/37), dropout rates (35/37),
intention-to-treat analysis (30/37), an appropriate and
clearly focused question (37/37), randomization process
(34/37), allocation concealment (27/37), blinding
(31/37), and group differences (33/37). When treatment
was conducted at multiple sites, 4 out of the 5 multisite
studies did not mention if results were comparable
across sites (Table 2). The 10 unique studies evaluating
multimodal approaches for chronic neck pain were all
rated for risk of bias as acceptable quality (+) according
to SIGN 50 RCT criteria [75–80, 82–85] (Appendix Table 2).
Categories that were poorly addressed include multisite
similarities (6/10) and group differences (6/10) (Table 2).
In general, we judged that all EVAT categories were
adequately addressed in terms of the recruitment and
participation of those intended for study. However, the
staff, places, and facilities in which the treatment was
being delivered were not always clearly described to
the reader (16/37 unimodal studies and 3/10 multimodal
studies). Several types of practitioners delivered the
treatment including physical therapists, chiropractors,
and massage therapy students, and in some studies,
multiple therapists delivered the interventions. Treatments
were commonly conducted at multiple locations,
as one would often see in real-life practice, including
private clinics, hospitals, and universities (Table 2).
Of the 37 unimodal RCTs, 12 reported that no
adverse events occurred during the study; 10 reported
minor adverse events, typically transient increases in
pain in the area of treatment or overall soreness. The
remaining 15 studies did not provide any information
on adverse events. Of the 10 multimodal studies, 2
reported minor adverse events such as muscle soreness
or increased pain or tiredness; one study reported that
no adverse events had occurred during the study. The
remaining 7 did not describe any adverse events or
mention whether they occurred during the study (Appendix
Tables 1 and 2).
We did not attempt meta-analysis for the multimodal
studies given the heterogeneity and varying
combinations of interventions being used for each program.
Overall, regardless of intervention types, half (n =
5/10) of the studies [76, 78, 79, 81–83] reported a positive
effect on pain outcomes; studies with nonthrust interventions trended toward greater pain reductions than
did interventions with thrust. Of the 8 studies measuring
disability as an outcome, 7 reported improved
function using a multimodal approach; only one study
assessed HRQoL as an outcome (Appendix Table 2).
The unimodal studies published since January 2000
comparing thrust to either sham (n = 5) or no treatment
(n = 3) included treatment of one dose/one day
(n = 5/8 studies) or varied in duration or types of interventions/
comparators, which prevented pooling. These
studies have small samples and show mixed results for
a reduction in pain; only one study measured disability
and 2 studied HRQoL. The studies comparing nonthrust
to either sham or no treatment (n = 4) were all of one
dose/one day treatment; 3 of the 4 studies did not
show any immediate reduction in pain; only one study
assessed disability as an outcome. The studies comparing
nonthrust to active comparators were also either
one dose/one day treatment or compared interventions
too different to pool (n = 4). There were also studies
comparing different styles or doses of thrust and/or
nonthrust (Appendix Table 1).
There were 6 studies the authors believed could
be combined and compared thrust interventions that
included an exercise regimen to exercise alone at
timepoints closest to 1, 3, and 6 months follow-up. The
authors believed meta-analysis could be attempted for
the outcomes of pain, disability, and HRQoL (Figs. 3–5).
The pooled SMD across 5 studies (535 patients) closest
to one month showed a nonstatistically significant reduction
in pain in favor of thrust plus exercise versus
exercise regimen alone (SMD = –0.37; 95% confidence
interval [CI], –0.77 to 0.03; P = 0.07; I2 = 81%).
into the VAS, this equates to a 9.25–point change on a
0–100 scale. A similar effect is noted (SMD = –0.27; 95%
CI, –0.60 to 0.06; P = 0.10; I2 = 64%) at 3 months across 5
studies (481 patients); at 6 months even less of an effect
is observed across 4 trials (473 patients) (SMD = –0.20;
95% CI, –0.54 to 0.14; P = 0.25; I2 = 70%) (Fig. 3). Across
these same studies, meta-analysis produced similar results
for a reduction in disability. At the timepoint nearest
one month, a nonstatistically significant reduction
in disability favored thrust plus exercise compared to
exercise alone (SMD = –0.35; 95% CI, –0.76 to 0.06; P =
0.09; I2 = 81%). Translated into the NDI, this equates to
a 4.4–point change on a 0–50 scale. SMD for a reduction
in disability at 3 months (SMD = –0.35; 95% CI, –0.70 to
0.00; P = 0.05; I2 = 68%), and at 6 months across 3 trials
(473 patients) (SMD = –0.12; 95% CI, –0.33 to 0.08; P =
0.23; I2 = 18%) (Fig. 4). HRQoL was pooled across 3 studies
closest to 1, 3, and 6 months (405 patients); at one
month (SMD = 0.19; 95% CI, –0.28 to 0.66; P = 0.43; I2 =
82%); at 3 months (SMD = 0.25; 95% CI, –0.30 to 0.80; P
= 0.38; I2 = 87%), and at 6 months (SMD = 0.07; 95% CI,
–0.46 to 0.59; P = 0.80; I2 = 86%) (Fig. 5).
Confidence in the Effect Estimates
Overall, risk of bias was not of serious concern
across all studies evaluated for systematic review. Methodological
quality of studies since 2000 is adequate.
However, heterogeneity was of serious concern for
this systematic review, and results are not consistent
across included studies. Clinical heterogeneity hindered
our ability to pool attempted subsets or categories of
studies and comparators as well as varying intervention
approaches, treatment doses, and duration of
studies reported in the literature. There were only 6
studies for which the authors judged meta-analysis to
be feasible. The studies looked at the effect of thrust
plus exercise versus exercise alone at timepoints of 1, 3,
and 6 months. As expected, we detected a statistically
significant degree of heterogeneity in these pooled
studies’ analyses except for closest to 6 months for
disability when the studies similarly report small or no
effect favoring either approach. Outcomes measures,
however, appear consistent, and report the VAS, NDI,
and SF-36 tools at varying timepoints. Sample sizes remained
small across studies. Although the studies were
directly related to our research question, inconsistency
and small sample size contributed to overall imprecision.
We did not detect any publication bias according
to either the Begg or Egger tests according to groupings
(data not shown). Considering these factors, our
confidence in the effect estimates are limited, and we
graded the overall literature pool as low to moderate
quality evidence. Our evaluation and Appendix Tables
1 and 2 display these different approaches preventing
There is low to moderate quality evidence that
various types of manipulation and/or mobilization will
reduce pain and improve function for chronic nonspecific
neck pain compared to other interventions. Many
of the previous reviews of chronic nonspecific neck pain
report evidence in favor of manipulation and mobilization
for patients with chronic neck pain. However, most
of these studies also report that methodological flaws
render the evidence insufficient or inconclusive, making
it inappropriate to conclude that manipulation and/
or mobilization are more effective compared to usual
care or other CIM therapies.
We relied on the evidence from previous reviews [8, 15, 19, 20] as a starting point for this review. The
Shekelle and Coulter  review found that there is
greater evidence for manipulation and mobilization
of chronic low back pain compared to chronic neck
pain. Both the Bronfort et al  systematic review
and the Shekelle and Coulter  systematic review
emphasized the need for future trials to examine welldefined
subgroups of patients, and to further assess
the value of manipulation and mobilization to establish
the optimal number of treatment visits. In 2010,
Gross et al  published a Cochrane Review on manipulation
and mobilization of neck pain. The Gross
et al  review reported conclusions similar to those
in our review and in the Bronfort et al  systematic
review (i.e., moderate evidence that thrust/nonthrust
is equal to or superior to general practitioner management
for short-term pain reduction for chronic neck
Other systematic reviews [12, 86] have also found
that therapies involving manual therapy (thrust/nonthrust)
and exercise are more effective than other noninvasive
alternative strategies for patients with chronic
neck pain. Vernon et al [87, 88] published 2 systematic
reviews on neck pain. They indicated moderate to
high quality evidence in support of spinal manipulation
or mobilization for chronic nonspecific neck pain. [8, 15, 19, 20, 87]
Strengths and Limitations
Although this review builds on previous efforts,
it adds to the literature base by including both manipulation
and mobilization interventions not only in
chiropractic settings, but in other noninvasive therapy
settings such as osteopathy, manual therapy, and physical
therapy. We attempted to sort the literature in the
most homogeneous fashion, predefining eligibility
criteria and specifying precise definitions with subject
matter experts. Still, few studies could be pooled for
meta-analysis. The methodological quality of studies
published since 2000 appears to be adequate overall;
few studies suffered from methodological flaws that
would risk biasing the reported results. However, the
studies remain heterogeneous in terms of dose, styles of
interventions, controls/comparators being used across
studies, and chronicity of patients is not always consistently
defined across studies included. We attempted
to create homogeneous subsets of data through the
current analysis. Doing so may have reduced the power
of calculations when only a small number of studies
could be pooled. Further research is likely to have an
important impact on the evidence.
Most systematic reviews that evaluate treatment
efficacy for musculoskeletal disorders such as chronic
neck pain give preference to including unimodal rather
than multimodal approaches. As noted previously,
studies with unimodal approaches can better isolate
(statistically) the individual effects of mobilization
and manipulation. In contrast, assessing the effect of
multimodal programs can be problematic, especially
when meta-analysis is desired. However, multimodal
programs may better represent “real-world” clinical
practice and may translate to clearer clinical knowledge
The approaches used in the multimodal intervention
studies are heterogeneous between, and in some
cases within, individual studies. Some studies evaluate a
specific standard program; some evaluate classificationbased
approaches in which patients are assigned therapies
based on an assessment of the etiology of their
pain; and some are pragmatic trials that allow practitioners
to choose specific treatments for each patient.
Because the study of multimodal programs is more difficult
than that for unimodal interventions, largely owing
to their heterogeneity, it is difficult to interpret the
evidence. However, these types of approaches are more
likely what one would see in practice.  As groups
such as chiropractors are accepted more widely in such
treatment settings and hospitals, the norm is likely to be
multimodal care. The majority of nonthrust multimodal
studies trended toward showing significant pain reduction
results compared to that of the thrust multimodal
studies. However, additional treatment modalities (e.g.,
prescribed exercises, stretches, massage, ultrasound,
education, or advice) were used in conjunction with
manual manipulation and mobilization treatments, so
the causal link between treatment and clinical effect
cannot be substantiated. This trend is also in contrast to
the unimodal studies, in which thrust interventions may
appear to be more effective than nonthrust in reducing
The research to support manipulation and mobilization
as a treatment for chronic nonspecific neck pain
is complicated and trying to dissect it to draw specific
conclusions proved challenging. Stakeholders, including
physicians and their patients, should have an active
voice at the table when identifying what will be most
impactful to them and building future research agendas.
This review can serve as a guide to the categories
of studies with strength areas for treating chronic neck
pain with manipulation and mobilization, and the settings
in which multimodal approaches were incorporated
in which there may be an increased benefit to
Although the focus of this review was on randomized
trials, it is important to note that available research
on manipulation and mobilization for the treatment of
chronic nonspecific neck pain encompasses study designs
other than the randomized controlled trial (e.g.,
cohort studies [both perspective and retrospective], observational
studies, and others). The use of observational
studies is important for building the evidence base in
which randomized trials are lacking or are insufficient
for the task (e.g., assessing adverse effects, identifying
best practices, and understanding disparities in access
to and delivery of health care services).
There is low to moderate quality evidence that
various types of manipulation and/or mobilization will
reduce pain and improve function for chronic nonspecific
neck pain compared to other interventions. The
methodological quality of the reported trials from 2000
to 2017 is adequate to evaluate. The studies remain heterogeneous
in terms of dosing, duration of treatment,
interventions, and comparators. For these reasons, it
remains a challenge to draw conclusions and have confidence
in any estimated effect that could be confirmed
as a benefit of mobilization and manipulation alone for
chronic neck pain beyond other therapies. Based only
on the trial literature to date, these therapies do appear
to be safe. However, large longitudinal studies are
needed to establish safety.
The authors would like to acknowledge the following
individuals for their technical and administrative
support throughout the project: Cindy Lentino, Viviane
Enslein, Chris Baur, John Bingham, Holly Chittum, Laurie
Davidson, and Judy Bearer.
Author contributions: Dr. Ian Coulter had full access
to all the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analyses. Drs. Coulter, Vernon, Hurwitz, and Herman—
with the support of Ms. Crawford and Dr. Khorsan—
designed the study protocol. Ms. Crawford, Ms. Booth,
and Dr. Khorsan managed the literature searches and
summaries of previous related work and wrote the first
draft of the manuscript. Drs. Coulter, Vernon, Hurwitz,
and Herman provided revision for intellectual content
and final approval of the manuscript.
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