Placebo response to manual therapy:
something out of nothing?
Joel E Bialosky1,2, Mark D Bishop1,2, Steven Z George1,2, Michael E
1Department of Physical Therapy,2Center for Pain Research and Behavioral Health, and3Department of Clinical
and Health Psychology, University of Florida, Gainesville, FL, USA
The mechanisms through which manual therapy inhibits musculoskeletal pain are likely multifaceted and
related to the interaction between the intervention, the patient, the practitioner, and the environment.
Placebo is traditionally considered an inert intervention; however, the pain research literature suggests that
placebo is an active hypoalgesic agent. Placebo response likely plays a role in all interventions for pain and
we suggest that the same is true for the treatment effects associated with manual therapy. The magnitude
of a placebo response may be influenced by negative mood, expectation, and conditioning. We suggest
that manual therapists conceptualize placebo not only as a comparative intervention, but also as a potential
active mechanism to partially account for treatment effects associated with manual therapy. We are not
suggesting manual therapists include known sham or ineffective interventions in their clinical practice, but
take steps to maximize placebo responses to reduce pain.
Keywords: Placebo, Pain, Manual therapy
Manual therapy is an effective intervention for
some individuals experiencing musculoskeletal pain
conditions.1,2Despite the clinical effectiveness, the
mechanisms through which manual therapy influ-
ences clinical outcomes are unknown. Common
clinical practices, including evaluative procedures,
are intended to identify hypo-mobile or mal-aligned
structures of interest and are followed by the
application of specific techniques meant to ‘correct’
the observed dysfunction, suggesting a biomechanical
mechanism. Manual therapists continue to follow
this model of clinical practice3,4despite literature
unreliable5and their findings do not affect clinical
outcomes.6Neurophysiological responses accompany
manual therapy interventions and are suggested as
pertinent to the mechanisms.7,8Currently, neurophy-
siological responses to manual therapy have been
studied primarily as an immediate within session
response,9–12and the relevance of these findings to
clinical outcomes is
Consequently, the effectiveness of manual therapy
may result from both biomechanical and neurophy-
Rehabilitation interventions such as manual ther-
apy are a ‘structured experience’13rather than applied
in isolation. Accordingly, the context of the treatment
including the technique, the provider, the participant,
the environment, and the interaction between these
Therefore, the effects of manual therapy are likely
related to multiple mechanisms. Placebo has a
hypothesized role in all pain-related clinical outcomes
including those associated with manual therapy14,15
and has received less attention than other potential
mechanisms. Interestingly, many of the neurophysio-
logical responses associated with manual therapy and
considered pertinent in the clinical outcomes are also
observed in placebo studies unrelated to manual
account for some of the changes in clinical outcomes
observed in response to manual therapy.
The traditional view of placebo is as an annoyance
capable of confounding study results.16,17In fact, one
of the highest levels of evidence, the randomized
controlled trial, frequently bases the success of a
studied intervention on the observed efficacy in
comparison to placebo. The implication being not
better than placebo is indicative of an ineffective
intervention. Additionally, placebo is often defined as
inert and a lack of a treatment effect has been
suggested as a requirement for a valid placebo for
manual therapy.18,19In contrast, recent literature
Correspondence to: J E Bialosky, Department of Physical Therapy,
University of Florida, PO Box 100154, Gainesville, FL 32610-0154, USA.
? W. S. Maney & Son Ltd 2011
Journal of Manual and Manipulative Therapy
suggests placebo is a psychologically and physiologi-
cally active process associated with a robust hypoal-
The current placebo literature
suggests, ‘The focus has shifted from the ‘‘inert’’
content of the placebo agent (e.g. starch capsules) to
the concept of a simulation of an active therapy
within a psychosocial context.’21Terms such as
placebo effects,22–24placebo response,22and meaning
refer to the context of the placebo
experience as related to the patient, the clinician,
the clinical environment, and the interaction of these
factors.23For instance, the magnitude of a placebo
response may vary depending on the participant–
researcher interaction.25As a result, we will define
placebo in this manuscript not as an inert agent, but
as a mechanism likely accounting for some of the
treatment effects of all interventions for pain includ-
ing manual therapy. Additionally, placebo mechan-
isms of manual therapy will be operationally defined
to include factors related to the patient, the clinician,
and the clinical environment beyond the specific
mechanical parameters of the intervention through
which manual therapy may alter musculoskeletal
The purpose of this manuscript is to present a non-
systematic review of placebo-related hypoalgesia and
the potential role of placebo as one of the mechan-
isms through which manual therapy alters musculos-
keletal pain conditions. Functional improvements are
also associated with placebo;26,27however, the focus
of the current manuscript is on placebo as a
mechanism of pain relief for manual therapy inter-
ventions in the treatment of individuals presenting
with musculoskeletal pain conditions. First, we will
consider the effectiveness of placebo in inhibiting
pain from different clinical pain studies. Second, we
hypoalgesia. Third, we will focus on identifying
individual characteristics likely to influence
magnitude of a placebo response and ethical con-
siderations in the use of placebo. Fourth, we will
discuss factors which affect the magnitude of the
placebo effect and how manual therapists may use
this to their advantage. Finally, we will discuss
limitations in the current manual therapy placebo
literature for which manual therapists should be
aware when reading and interpreting studies incor-
porating placebo. We will cite work from the pain
research literature in order to accomplish these goals
with the intention of translating this literature to
manual therapy mechanisms and practice.
Effectiveness of the Placebo
Placebo is an active hypoalgesic agent; however, the
effect is variable and dependent upon the context in
which the placebo is administered. For example, a
systematic review28and subsequent follow-up29con-
cluded that placebo had a small, significant effect on
clinical pain (mean reduction: 6.5 and 6 mm on a
100 mm visual analog scale respectively, Cohen’s
d50.27 and 0.25 respectively). In contrast, Vase
et al.30conducted separate meta-analyses of studies
in which placebo was a comparative intervention and
studies specifically of the placebo effect. These study
designs differ in that participants in a placebo
controlled study are instructed that they will receive
either the studiedintervention
participants are provided with a placebo with an
instructional set intended to enhance expectation for
the effectiveness of the placebo (‘the agent you have
just received is known to powerfully reduce pain in
some patients’).31Vase et al.30noted a small effect
size (Cohen’s d50.15) in studies of placebo as a
comparative intervention; however, a large effect size
(Cohen’s d50.95) in studies designed to specifically
investigate placebo mechanisms.30Vase et al. further
noted similar findings in a more recent follow-up to
Factors other than the study design (placebo as a
control versus placebo as a mechanism) may also
influence the magnitude of placebo hypoalgesia. The
magnitude of placebo hypoalgesia may increase over
time in a visceral pain model in participants present-
ing with irritable bowel syndrome,31increase with
repeated exposure in healthy participants exposed to
experimental pain,32and last up to a week following
the initial application in healthy participants exposed
to experimental pain.33However, the duration of the
placebo effect is not established in studies of
Subsequently, the literature suggests a consistent
hypoalgesic effect of placebo, although the related
hypoalgesia is variable in magnitude and dependent
upon the study design (placebo control versus
placebo as a mechanism), and appears time and dose
of placebo mechanisms,
Mechanisms of Placebo-related Hypoalgesia
Placebo hypoalgesia may result from a number of
potential mechanisms. Nonetheless, expectation and
conditioning are two of the primary mechanisms and
will be the focus of this manuscript.
Expectation as a mechanism of placebo-related
The magnitude of placebo-related hypoalgesia is
dependent upon expectation or what the individual
thinks will happen.20,30For example, Verne et al.
found lidocaine gel to provide a superior hypoalgesic
effect to placebo saline for visceral pain sensitivity in
individuals with irritable bowel syndrome in a
standard placebo controlled study.34Additionally,
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Bialosky et al. Placebo response to manual therapy
Journal of Manual and Manipulative Therapy