Contextual factors, placebo and nocebo effects in physical therapy: clinical relevance and impact on research
Creators: name: ROSSETTINI, GIACOMO
Publisher: name: Universit� degli studi di Genova
Year: 2018

description: A brief overview on placebo and nocebo effects
Placebo and nocebo effects represent one of the most fascinating topics in the
healthcare field. They represent complex and distinct psychoneurobiological
phenomena where behavioural and neurophysiological changes occur during an
interaction between the patient and the healthcare context (1). Placebo effects (Latin ?I
shall please?) are produced by a psychosocial context that is capable of positively
affecting the patient's brain and therapeutic outcomes (2-4). On the contrary, nocebo
effects (Latin ?I shall harm?) are consequences of the negative perception of the ritual
and therapeutic act on the patient's mind and body, so much so that it generates
unwanted effects and side effects (5-7).
Throughout the history of medicine, placebo and nocebo have been traditionally
viewed as bothersome variables to check for in a clinical trial. In the last four decades,
in light of some significant clinical and laboratory findings, they have become a source
of research interest. Indeed, placebo and nocebo have been adopted as a conceptual
model to examine the body-mind interaction and the human body systems, exploring
their connection with different systems, mechanisms, diseases and therapeutic
interventions (8, 9). In particular, placebo and nocebo effects have been studied in mood
(10), cardiovascular, respiratory (11), gastrointestinal (12, 13), motor (14), immune and
endocrine (15), and pain systems (16-18).
Clinically, not all improvement or aggravation of patients? symptoms is due to
placebo and nocebo effects. It is necessary to rule out the patients? modifications
created by placebo and nocebo effects from the changes of outcomes related to other
confounding elements. The elements which could create misinterpretations of the
patients? clinical picture are: the spontaneous remission of the disease and symptom
fluctuation (also called the natural history), the regression to the mean (a statistical
phenomenon caused by selection biases), the patient?s and clinician?s biases during the
reports of clinical conditions, and unidentified effects of concomitant co-interventions
(8, 9).
Different psychoneurobiological findings allowed the scientific community to
begin to understand the underlying mechanisms of placebo and nocebo effects. From a
theoretical perspective, two main psychological subjective constructs have been
suggested to explain how placebo or nocebo effects act: the expectation and the
conditioning. The social learning, reward, anxiety reduction, desire, motivation,
memory, somatic focus, genetic and personality traits also represent alternative theories
(19-25). ?Alternative? however does not mean that these psychological mechanisms are
mutually exclusive: they can interact simultaneously (26).
Regarding the actual findings, placebo and nocebo interact with the brain
modulatory systems at a neurochemical level, through the release of specific
neurotransmitters. For instance, considering pain outcome as a model, the endogenous
opioids, dopamine, cannabinoids, oxytocin and vasopressin are involved in placebo
analgesia, while cholecystokinin, dopamine, opioid deactivation and cyclooxygenaseprostaglandins
activation are implicated in nocebo hyperalgesia (27-29).
Furthermore, recent advances in neuroimaging techniques, such as functional
magnetic resonance imaging (fMRI) and positron emission tomography (PET), suggest
an involvement of specific neural correlates during placebo and nocebo effects, mainly
the pain one. In fact, placebo and nocebo are able to activate or deactivate the four key
brain regions commonly associated with the descending pain processing pathway: the
dorsolateral prefrontal cortex, the rostral anterior cingulate cortex, the periaqueductal
gray and the dorsal horn of spine (16). Nevertheless, they represent only a part of brain
areas showing a change in their activity during placebo or nocebo (30-32).
Therefore, the previously described evidence suggests that placebo and nocebo
effects are concrete and genuine phenomena, triggered by different contexts, and
capable of impacting the patients? brain. It is necessary to define what the context is,
and why its parts are important from a clinical perspective (33).
The healthcare context as a trigger of placebo and nocebo effects
In 1955 Balint described the context as the ?whole atmosphere around the
therapy? (34). The context is not a vacuum, but it embodies a healing space composed
by internal, external and relational elements capable of interacting with the patient?s
disease (35). The internal elements consist of memories, emotions, expectations and
psychological characteristics of the patient. The external elements include the physical
aspects of therapy, such as the kind of treatment (pharmacological or manual) and the
place in which the treatment is delivered. Relational elements are represented by all the
social cues that characterize the patient-clinician relationship, such as the verbal
information that the clinicians give to the patient, the communication style or the body
language (36).
In 2001, Di Blasi et al. defined these elements as ?contextual factors?. These
factors have been grouped, from a clinical practice point of view, in five categories: a)
clinician features, b) patient features, c) patient-clinician relationship, d) intervention
features, and e) healthcare setting features (37). As a whole, contextual factors
constitute the therapeutic ritual and healing symbols surrounding the patient-clinician
encounter, capable of producing changes in the patient at perceptual, neurophysiological
and cognitive levels (38). Indeed, contextual factors convey a hidden meaning, actively
detected and analysed by the patient, which is essential for the perception of care and
the interpretation of the therapeutic intervention (39, 40). When these contextual stimuli
and cues are filtered by the patient?s perspective and mind-set (41), they are translated
into a complex cascade of psycho-neuroimmunoendocrine events, thus triggering
placebo and nocebo effects and influencing the course of illness (42, 43).
From a clinical perspective, the contextual factors pervade every healthcare action
(history taking, physical examination, therapy and prognosis) and directly affect the
quality of the health-related outcome (44-46). A positive context, that is characterized
by the presence of positive contextual factors, can improve therapeutic outcome by
producing placebo effects, while a negative context, characterized by the presence of
negative contextual factors, can aggravate therapeutic outcome by creating nocebo
effects(47, 48). For example, during the same treatment delivery (e.g. painkillers), the
use of positive verbal suggestion (e.g. ?This therapy will help you and it will decrease
pain?) can improve musculoskeletal pain, while the adoption of verbal suggestion of
uncertainty (e.g. ?This therapy could help you and sometimes it decrease pain?) can
aggravate patient?s pain (49).
The presented studies offer a starting point for reflection about the role of the
contextual factors surrounding the administration of a healthcare treatment: they can be
a source of improvement of the efficacy of the therapy or implicated in the
manifestation of adverse effects. The logical consequence is to wonder whether context,
placebo and nocebo effects have been taken into consideration in a specific healthcare
field, such as physical therapy.
The link between placebo, nocebo effects and physical therapy
Throughout the history of physical therapy and rehabilitation, placebo and nocebo
effects have been considered as problematic phenomena for two main reasons. From a
research point of view, they have represented confounding factors capable of limiting
the internal validity of the study design and reducing the external validity of the
findings (50). From a clinical point of view, they have embodied troublesome and nonspecific
variables able to attenuate the therapeutic role of specific therapies such as
massage, joint mobilization and therapeutic exercise (51, 52). As a consequence, for
many years the role of placebo and nocebo effects was debated worldwide by clinicians
and researchers (53-55).
At the end of the first decade of the twenty-first century the scientific community
began to investigate the mechanisms of action of joint, soft tissue and neural therapeutic
intervention, consequently revaluing the role of placebo and nocebo effects in
physiotherapy (56). Recent studies have suggested a mechanical and neurophysiological
mechanism (peripheral, spinal and supraspinal) linked to the therapeutic strategies
adopted by physical therapists (57). Among the supraspinal mechanisms, the placebo
and nocebo effects have assumed an important top-down role in inducing changes in
patient?s symptoms (58), thus becoming elements that clinicians should adopt in clinical
practice (59).
Recently, also the context in which interventions are delivered has been suggested
as a moderator of clinical effects (60). A new line of research has indicated the context
as responsible for a larger non-specific component of treatment efficacy in physical
therapy (61). Despite these promising advances, the following issues remain
unexplored:
1) What are the contextual factors?
2) How can the contextual factors trigger placebo and nocebo effects?
3) Which therapeutic outcomes can be influenced by the contextual factors?
4) Are the physical therapists aware of the use of contextual factors in clinical
practice?
5) What is the role of contextual factors in research?
General organization of the research project
The main goal of this PhD research project is to investigate the relevance of the
contextual factors as triggers of placebo/nocebo effects and their impact on therapeutic
outcomes in physiotherapy. Different studies were conducted during the 3-year period
of PhD training (2015-2018). The results, relative discussions and implications are
reported in the chapters of the present dissertation as follows:
? Chapter I: a conceptual model regarding the role of the contextual factors as
triggers of placebo, nocebo responses and influencers of physical therapy outcomes;
? Chapter II: the model of contextual factors regarding musculoskeletal pain, which
is a common outcome encountered by physical therapists;
? Chapter III: the link between the determinants of patient satisfaction in outpatient
musculoskeletal physiotherapy clinics and the contextual factors;
? Chapter IV: the knowledge, attitude and behaviour of Italian physiotherapists
specialized in manual therapy towards contextual factors;
? Chapter V: the translational value of contextual factors and their relevance for
physical therapy research.