[ viewpoint ]

JOEL E. BIALOSKY, PT, PhD1,2 MARK D. BISHOP, PT, PhD1 CHARLES W. PENZA, DC, PhD1

Placebo Mechanisms of
ManualTherapy: A Sheep
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inWolfs Clothing?
J Orthop Sports Phys Ther 2017;47(5):301-304. doi:10.2519/jospt.2017.0604

W
Copyright 2017 Journal of Orthopaedic & Sports Physical Therapy. All rights reserved.

hen a physical therapist provides a manual therapy (MT) participants are aware from the consent
intervention for a patient presenting with pain and the process of the chance of receiving a pla-
patient experiences a positive clinical outcome, we cannot cebo treatment.27 Placebo analgesia is
much larger when the placebo treatment
answer as to why this occurs. Still, the Commission on
is provided with an instructional set en-
Accreditation in Physical Therapy Education mandates that MT be hancing expectation (eg, the agent you
taught in entry-level physical therapy programs and that practicing have just received is known to powerfully
clinicians seek continuing education and fellowship opportunities. reduce pain in some patients).28 Placebo
Would we continue to devote valuable tervention without a treatment effect. In analgesia is further augmented when
Journal of Orthopaedic & Sports Physical Therapy

time and financial resources to learning contrast, placebo treatments are associ- participants are conditioned to expect
and improving our skills in providing MT ated with marked analgesia.27 Further- analgesia through researchers surrepti-
interventions if the related clinical out- more, the placebo response is an active tiously lessening a painful stimulus after
comes were placebo responses? In this neurophysiological process associated the treatment21 or surreptitiously replac-
Viewpoint, we conceptualize placebo as with consistent responses in both the spi- ing a medication with a placebo.1 Fur-
an active and important mechanism of nal cord10 and supraspinal regions.9 Col- thermore, increased placebo analgesia
MT. We are not suggesting that placebo lectively, these findings support multiple is observed following a previous positive
is the only pathway through which MT endogenous pain modulatory processes response18 and after watching another
inhibits pain; however, we argue that pla- in response to the expectation of receiv- person experience pain relief in response
cebo mechanisms deserve consideration ing care. to a treatment.6 Subsequently, placebo
as an important component of the treat- analgesia is increased when participants
ment effect. For the sake of brevity, we The Placebo Treatment-Effect (1) believe they have received an effective
will focus on placebo as a mechanism of Mechanism analgesic agent, (2) are conditioned to
MT-related pain relief, and from here on Placebo effects result from the psycho- expect a placebo intervention to be effec-
will refer to pain relief corresponding to social context surrounding the clinical tive, (3) are conditioned with an effective
a placebo treatment as placebo analgesia. encounter and are reliably produced treatment and then given a placebo treat-
in laboratory settings by manipulating ment, and (4) have had prior successful
Not Your Fathers Placebo expectations and through conditioning experiences and/or when the environ-
Traditionally, placebo has had a nega- and learning. Placebo analgesia is small ment includes other persons benefiting
tive connotation, implying an inert in- in placebo-controlled studies, in which from the treatment.
1
Department of Physical Therapy, University of Florida, Gainesville, FL. 2Brooks RehabilitationCollege of Public Health and Health Professions (University of Florida) Research
Collaboration, University of Florida, Gainesville, FL. No funding support was received. Institutional Review Board approval was not required for this study. The authors certify that
they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article. Address
correspondence to Dr Joel E. Bialosky, Department of Physical Therapy, University of Florida, PO Box 100154, Gainesville, FL 32610. E-mail: bialosky@phhp.ufl.edu t Copyright
2017 Journal of Orthopaedic & Sports Physical Therapy

journal of orthopaedic & sports physical therapy|volume 47|number 5|may 2017|301

 [ viewpoint ]
Placebo Mechanism Considerations of MT Variability in Response to MT mannerisms and beliefs of the provider
In a famous scene from Raiders of the Attempts to identify individuals who are are likely to play a key role in the clinical
Lost Ark, Indiana Jones is confronted likely to respond positively to MT13 have effectiveness of MT.
by a skilled swordsman. The swords- been unsuccessful. The placebo response
man pulls out his weapon and undergoes is a complex, individualized experience Therapeutic Benefits From the Act of
elaborate swordplay as he prepares for influenced by multiple factors, and all Treatment
the battle. Indiana Jones calmly pulls individuals are likely placebo responders; Treatment response is dependent on
out a gun and shoots the swordsman. however, the magnitude of the placebo many factors, including those related to
The humor in this scene results from the response and conditions under which simply seeking and receiving care. Recent
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contrast between the theatrical, choreo- each person responds are highly vari- studies have observed analgesia exceed-
graphed approach of the swordsman and able.15 Placebo responses are mislabeled ing natural history of the disorder when
the apathetic approach of Indiana Jones. as nonspecific, implying a general effect individuals are aware of having received a
Manual therapy, at face value, resembles across interventions. Instead, placebo placebo (open-label placebo).16 Such find-
Indiana Jones, that is, an intervention responses are highly specific and depen- ings suggest that patients benefit from
without fanfare; however, in clinical dent on the individual intervention. For the act of receiving treatment, and part of
practice MT is accompanied by an elabo- example, placebo analgesia conditioned the treatment response to MT may be at-
rate ritual involving the evaluative and through opioid agents is abolished by tributed to the process of receiving care.
application process and more closely opioid antagonists, whereas placebo an-
resembles the swordsman. Though the algesia conditioned through nonsteroidal Next Steps for Research: Determining the
Copyright 2017 Journal of Orthopaedic & Sports Physical Therapy. All rights reserved.

choreographed dance of the swords- anti-inflammatory agents is not.1 Placebo Contribution of the Placebo Mechanisms
man does not serve him well, the ritual analgesia varies within individuals, sug- to MT
surrounding MT may play a major role gesting a state-dependent event rather Placebo-Controlled Trials of MT: Have
in the corresponding outcomes. In the than an individual characteristic,30 and We Been Comparing Good Apples to
following sections, we present findings analgesia to one form of placebo does not Bad Apples? A placebo comparator for
from the placebo literature with implica- predict analgesia to another form of pla- a medication is seemingly simple, as the
tions for interpreting patient responses cebo.20 Subsequently, placebo analgesia active ingredient and biological mecha-
to MT. is a specific and individualized response nism are generally well established. Man-
to the context of a provided intervention. ual therapies are complex interventions,
Journal of Orthopaedic & Sports Physical Therapy

MT Is an Experience Similarly, identifying MT responders and the active mechanisms behind their
Placebo analgesia is influenced by con- may be insensitive to the mean findings clinical effectiveness are not established.
textual factors. Physical placebo treat- of larger studies and dependent on indi- Consequently, a suitable placebo compar-
ments, such as placebo injections, vidual patient beliefs, experiences, and ator lacking the specific key ingredients
acupuncture, or surgery, result in greater relationship with the provider. of an MT intervention is elusive.
analgesic responses than oral placebos.2 Blinding of both the patient and pro-
Additionally, the magnitude of placebo The Manual Therapists Role in Contextual vider is an important consideration in
analgesia is dependent on the corre- Enhancement placebo-controlled trials. Blinding may
sponding meaning. For example, greater Placebo analgesia is enhanced by a posi- be compromised due to poorly designed
analgesia is observed when placebos are tive and empathetic provider.17 Similarly, placebos that are not believable. Further-
presented as more expensive,29 as well as the interaction between the provider and more, blinding may be lost due to sensa-
when they are labeled with a recognizable patient is influential in interventions for tions unique to the studied intervention22
brand name.4 Manual therapy is a physi- pain such as medication7 and electrical or side effects in the active arm.26 Similar
cal intervention provided by enthusiastic stimulation.11 In addition, provider ex- loss of blinding may occur in MT trials
practitioners who readily inform their pectations influence placebo analgesia.12 if the active arm is more elaborate (ie,
patients of its likely benefits. The physi- Specific to MT, provider expectations in- a skilled hands-on MT intervention) or
cal nature of MT along with the positive fluence the manner of interacting with prone to side effects such as transient
framing so often provided by practitio- the patient,24 and provider preferences soreness. Expectation is an important
ners may effectively alter or reinforce the are associated with clinical outcomes.8 consideration, as an MT placebo compar-
patients beliefs and perceptions of the Collectively, these findings suggest that ator may successfully blind participants;
intervention influencing the related out- the provider communication style, as well however, it may also be associated with
comes. Subsequently, the MT and provid- as beliefs, may influence placebo analge- low expectations for its effectiveness.
er brand should be considered for their sia and clinical outcomes in response to For example, a skillfully applied MT in-
role in clinical outcomes. interventions for pain. Subsequently, the tervention for which participants have

302|may 2017|volume 47|number 5|journal of orthopaedic & sports physical therapy

 high expectations may result in superior to be shot by Indiana Jones (active arm), in clinical care. Carefully designed stud-
outcomes to a light-touch comparator for while half are assigned to be impaled by ies are necessary to account for the true
which participants have lower expecta- the swordsman (placebo arm). We would magnitude of these factors on outcomes
tions. Furthermore, the same MT inter- likely conclude that Indiana Jones was and may provide a more valid indication
vention may lack efficacy when compared ineffective due to his inability to outper- both of the effectiveness of MT as well as
to a sham MT that is similar in context form the swordsman. Equivocal findings of the extent of placebo mechanisms in
to the studied MT and for which par- between Indiana Jones and the swords- the observed clinical outcomes.
ticipants have higher expectations. Sub- man (placebo) do not necessarily imply Is There an Additive Effect Between Pla-
sequently, the superiority, or failure to the ineffectiveness of Indiana Jones but, cebo and MT? Randomized controlled
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demonstrate superiority, of the studied instead, may suggest 2 equally effective trials assume an additive effect, implying
MT intervention to a placebo treatment interventions. A third, no-treatment arm that the treatment effect is the difference
may be related to the expectations attrib- would allow us to determine whether In- between the response to the studied in-
uted to each. diana Jones and the swordsman resulted tervention and the response to the pla-
Potentially, even more challenging in larger and more meaningful outcomes cebo treatment. The assumption of an
and problematic is blinding the provid- than natural history and could argue for additive effect is not established for MT,
er to whether he or she is providing the the effectiveness of both. Studies of the and placebo treatments may represent
real or the placebo intervention. Pro- mechanisms of MT should account for the separate but at times equally effective
vider blinding has implications for out- magnitude of placebo mechanisms, with interventions. Furthermore, the total
comes due to the known effect of provider additional mechanisms beyond placebo treatment effect of MT may represent
Copyright 2017 Journal of Orthopaedic & Sports Physical Therapy. All rights reserved.

preferences,8 as well as unconscious bias considered to account for the remaining interacting (MT and placebo) mecha-
in interacting with patients.24 treatment effect. nisms.19 For Indiana Jones, a gun without
Placebo may be a primary mechanism Placebo as a Mechanism of MT Rather fanfare was effective. In the case of MT,
through which MT interventions exert Than a Control for MT Participants in a however, the ritual may be the active in-
their effect on pain. As such, placebo-con- clinical trial may differ from those seek- gredient or may be necessary for the in-
trolled trials of MT may not be optimally ing care in terms of their expectations for tervention to maximally influence pain.
designed to determine clinical effective- treatment (patients do not enter treat- The strictly additive solution should not
ness, and carefully designed studies with ment expecting to receive a placebo) be assumed, and determining whether
appropriate placebo comparators and and preferences (individuals with strong the sword and the gun are separate but
Journal of Orthopaedic & Sports Physical Therapy

rigorous blinding may result in repeated preferences for MT may not participate equally effective interventions of differ-
null findings or clinically meaningless ef- in clinical trials knowing that they could ing underlying mechanisms, as well as
fect sizes. Manual therapy efficacy studies be assigned to a different treatment the degree to which the dance interacts
that include placebo comparators should arm). Participants in placebo-mecha- with the sword to enhance its effective-
account for blinding, as well as partici- nism studies receive a placebo treatment ness, is imperative to our understanding
pant and provider expectation, in each with instructions suggesting an effective of the mechanisms of MT.
study arm. intervention. This study design is more
Determining the Placebo Effect Size of consistent with clinical care, in which Reframing the Placebo Mechanism
MT A placebo treatment corresponds to interventions are provided by enthusias- Manual therapy is diverse, encapsulat-
a placebo response caused by the placebo tic practitioners instructing the patient ing differing approaches with markedly
mechanism, along with other factors, of the likely effectiveness. Placebo anal- different theoretical mechanisms. Head-
such as natural history of the disorder and gesia is greater in placebo-mechanism to-head comparisons consistently ob-
regression to the mean. The placebo effect studies than in placebo-control studies,27 serve that one type of MT is as effective
is the difference between the placebo re- and similar approaches may result in a as another for pain, despite the differing
sponse and changes occurring in response more accurate representation of the mag- theories and approaches, suggesting a
to no treatment (ie, the natural history of nitude of the placebo effect size of MT in common, shared mechanism. Manual
the disorder), within an experimental de- clinical practice. Furthermore, placebo- therapists, having invested large amounts
sign that can account for influences such controlled studies may underestimate the of time perfecting their craft, may be
as natural history of the disorder and re- effect size of MT as well.23 Collectively, troubled by the prospect of placebo as
gression to the mean.3 Imagine the scene these findings suggest that randomized a primary mechanism. Rather, placebo
from Raiders of the Lost Ark as a random- controlled trials underestimate both the mechanisms are active neurophysiologi-
ized controlled trial, with the swordsman, placebo and treatment effect sizes due cal effects generated and influenced by
in this example, considered as the pla- to differences in participant preferences the expectations and experience of receiv-
cebo. Half the participants are assigned and expectations from those observed ing skilled treatment from a rigorously

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 [ viewpoint ]
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