Fear reduction in patients with chronic pain: a learning theory perspective.

Abstract

Acute pain informs the individual that there is an imminent threat of body damage, and is associated with the urge to escape and avoid. Fear learning takes place when neutral stimuli receive the propensity to predict the occurrence of pain, and when defensive responses are initiated in anticipation of potential threats to the integrity of the body. Fear-avoidance models have been put forward featuring the role of individual differences in catastrophic interpretations of pain in the modulation of learning and avoidance. Based on extensive literature on fear reduction in anxiety disorders; cognitive-behavioral treatments have been developed and applied to patients with chronic pain reporting substantial pain-related fear. In this article, we discuss mechanisms underlying the acquisition, the assessment and extinction of pain-related fear through the cognitive-behavioral treatment of pain-related fear. Finally, we provide a number of critical notes and directions for future research in the field of chronic pain and pain-related fear.

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Fear & avoidance in chronic pain
Chronic pain is defined as “pain that extends
beyond the expected period of healing” [1]. In a
large pan-European survey, 19% of the popula-
tion was found to suffer from chronic pain of
moderate-to-severe intensity, with serious effects
on the quality of their social and working lives.
The reported pain was mainly of musculoskel-
etal origin, but headaches were also included [2].
Chronic pain patients are at increased risk for
the development of psychiatric conditions;
12.5–16.6% of the population in developed and
developing countries meet the Diagnostic and
Statistical Manual of Mental Disorders (DSM)
criteria for anxiety disorders and depression
[3], and an even larger proportion reports com-
plaints in the anxiety and depression spectrum
[4]. Besides the individual burden, chronic pain
accounts for high socioeconomic costs [5] due to
healthcare utilization [6], sick leave from work [7]
and reduced work effectiveness [8]. Due to both
human suffering and high economic costs, it has
been acknowledged that there is “a worldwide
chronic pain crisis” [9].
An important feature of chronic pain is that
biomedical models mostly cannot adequately
explain the experience of pain and disability,
since they presume a direct relationship with
structural and biomedical abnormalities, which
can not be found in many patients with chronic
pain [10–12]. The mechanisms by which pain
patients might be ‘trapped’ in a downward spiral
of increasing avoidance, disability and pain are
captured in several fear-avoidance models [13,14].
These models assume that individuals who
(mis-)interpret pain in terms of its worst possible,
most extreme negative consequences, called pain
catastrophizing [15], are likely to develop fear of
pain for events and situations they associate with
pain. This fear initiates avoidance and escape
behaviors that can have pain-reducing effects in
the short term. Nevertheless, a long-term conse-
quence of sustained avoidance of activities is the
risk for increased disability, which may in turn
reinforce further pain experiences and negative
thoughts, completing a downward spiral [16,17].
Fear avoidance beliefs might lead to the devel-
opment and maintenance of chronic pain [18].
Cross-sectional studies demonstrated that pain-
related fear predicts self-reported disability and
physical performance in acute [19] and chronic
pain [20,21]. The same relationship was found in
some prospective studies [22,23]. However, not all
evidence supports the role between pain related
Marlies den
Hollander†1,2,
Jeroen R de Jong1,2,
Stéphanie Volders3,
Mariëlle EJB Goossens2,
Rob JEM Smeets1,2,4
and Johan WS
Vlaeyen2,3
1University Medical Centre Maastricht,
Maastricht, The Netherlands
2Maastricht University, Maastricht,
The Netherlands
3University of Leuven, Leuven, Belgium
4Centre of Expertise in Rehabilitation,
Hoensbroek, The Netherlands
†Author for correspondence:
Department of Clinical Psychological
Science, Maastricht University,
PO Box 616, 6200 MD Maastricht,
The Netherlands
Tel.: +31 433 881 582
Fax: + 31 433 884 155
marlies.denhollander@
maastrichtuniversity.nl
Acute pain informs the individual that there is an imminent threat of body damage, and is
associated with the urge to escape and avoid. Fear learning takes place when neutral stimuli
receive the propensity to predict the occurrence of pain, and when defensive responses are
initiated in anticipation of potential threats to the integrity of the body. Fear-avoidance models
have been put forward featuring the role of individual differences in catastrophic interpretations
of pain in the modulation of learning and avoidance. Based on extensive literature on fear
reduction in anxiety disorders; cognitive–behavioral treatments have been developed and
applied to patients with chronic pain reporting substantial pain-related fear. In this article, we
discuss mechanisms underlying the acquisition, the assessment and extinction of pain-related
fear through the cognitive–behavioral treatment of pain-related fear. Finally, we provide a
number of critical notes and directions for future research in the field of chronic pain and
pain-related fear.
Keywords: chronic pain • conditioning • extinction • learning • pain-related fear
Fear reduction in patients
with chronic pain: a learning
theory perspective
Expert Rev. Neurother. 10(11), 1733–1745 (2010)
THeMed ArTICLe y Pain
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fear and chronicity. A review of nine studies measuring fear of
pain at baseline concluded that a causal link between fear avoid-
ance and poor long-term outcomes is weak [24]. Some evidence
was found that the role of fear is more prominent in a chronic
pain state [24]. Lakke et al. reviewed risk and prognostic factors
for nonspecific musculoskeletal pain in nine cohort studies and
concluded that fear avoidance beliefs are not a prognostic factor
for low back pain [25]. This conclusion is in line with the findings
from a recent prospective cohort study evaluating 20 possible
factors to influence disability at 6 months [26]. Catastrophizing
and fear avoidance were not significantly related to outcome at
6 months, neither was depression. Factors that were found to be
related to disability in primary care were perception of personal
control, acute-chronic timeline, illness identification and pain
self-efficacy [26]. However, this study may suffer from a problem
of semantic proximity among items of the self-efficacy and dis-
ability measures used. By contrast, a recent path analysis solved
some methodological weaknesses from earlier studies and found
supporting evidence for the different factors of the fear avoidance
model [27].
In summary, chronic pain is a problem that needs scientific
and clinical attention. Fear-avoidance models describe possible
mechanisms for the development and maintenance of chronic
pain, but since evidence is not conclusive, more research is needed.
A learning perspective on pain-related fear
By virtue of its biological significance, pain is an important moti-
vator in learning. Indeed, pain informs the individual that there
is the imminent or actual threat of body damage. Therefore, pain
is an unconditioned stimulus (US) that activates an immediate
defensive response. Here, we first address the adaptive value of
fear in acute versus chronic pain, and vulnerability factors to
acquire pain-related fear. Next, learning mechanisms by which
pain-related fear can be acquired and the different forms of defen-
sive behaviors in acute and chronic pain will be described.
Both pain and fear are important for an organism’s survival.
From this point of view, pain is adaptive in evoking fear, since it
elicits a response aimed at protecting the integrity of the body. In
acute pain, this is an adaptive response to prevent further blood
loss or damage. In chronic pain, the complexity of pain increases
and the role of physical damage often becomes questionable
[10–12]. A response driven by pain-related fear, such as avoidance
and hypervigilance, might not serve the hard-wired function
to recover anymore, but paradoxically may lead to detrimental
effects, as described in the fear-avoidance models. An initial injury
can occur without pain, especially when escape from a threat
source is urged first [28]. When in a relatively safe context, both
humans and animals need to express behavior aimed at healing.
In the article by Wall, it is concluded that pain is initiating this
behavior, instead of signaling tissue damage. Anxiety is described
as being part of the acute pain experience, aimed at providing a
safe environment for recovery. In the period that follows, inac-
tivity promotes the recovery of tissue damage. Wall mentioned
previously that this state might be prolonged beyond the necessary
time for healing. He concludes that the presence and intensity
of pain are too poorly related to the degree of damage for it to
be considered as a signal of tissue damage, an idea that has been
extensively proved to be right [10,12,29,30].
Despite the salience of pain experiences, there is individual
variation in the extent to which pain is experienced as aversive.
According to personal characteristics, the threat value of pain
(US) may vary between individuals. Pain catastrophizing [31]
and anxiety sensitivity [32] have been suggested to account for
these individual differences. Pain catastrophizing is defined as
an exaggerated negative interpretation of actual and anticipated
pain experience [31,33]. For example, people with high levels of
catastrophizing are convinced that pain means that their body is
vulnerable and needs careful protection to prevent further harm.
Anxiety sensitivity is a cognitive style by which the individual
tends to interpret anxiety-related symptoms in a way that gives
rise to a fearful reaction [34]. Pain catastrophizing and anxiety
sensitivity make people more responsive to painful stimuli and
more vulnerable to learn to anticipate the potential occurrence of
threatening pain [31,32,35,36]. For example, people with high levels
of anxiety sensitivity who experience increased muscle tension are
more likely to attend to these internal bodily sensations, and may
believe that they are at risk for a new pain episode [37].
In direct response to the presence of threat and the activation
of fear, defensive behaviors arise that may have cognitive, moti-
vational and physiological features [38]. Cognitive shifts occur to
detect threat and narrow attention to potential threat cues (known
as hypervigilance) [39,40]. Pain captures attention to orientate the
individual to the source of threat and engage in behaviors that,
in acute pain, promote healing, such as escape and avoidance
behavior [21]. Physiological arousal may be associated with muscle
contractions around the injured area; it is suggested that in acute
pain these muscle contractions and associated immobilization
may have the function to protect the body from further injury
[41]. Safety-seeking behavior is defined as a behavior intended to
prevent or minimize a feared catastrophe [42,43]. Safety-seeking
behavior in chronic pain includes not only avoidance (e.g., ‘‘I
won’t lift anything heavy because that would damage my back’’)
and escape behaviors (e.g., ‘‘I’ll stop sweeping the floor at the
first sign of pain because pain means that I damage my back’’),
but also subtle behaviors that are performed to prevent the feared
catastrophe while remaining in the feared situation (e.g., ‘‘I’ll
make sure that I don’t lean forward when I’m holding something
heavy because that might break my spine’’) [44].
Regardless of the threat value, people have the urge to reduce
the impact of any aversive US. This innate mechanism drives
learning, since people search for stimuli that predict or signal
the possible threat of the occurrence of the biologically relevant
US in order to be able to properly adjust their behavior. Learning
about the associations between stimuli is based on classical (or
respondent) conditioning, learning what is adequate behavior
regarding this new association is based on instrumental (or oper-
ant) conditioning. For example, a tennis player who experiences a
shooting pain in the back during a game (classical conditioning)
may start avoiding tennis (instrumental conditioning). By asso-
ciative learning a former neutral stimulus becomes a conditioned
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stimulus (CS), acquiring a new ‘predictive’ meaning by being
causally or functionally associated with a US [45]. This can be
understood from the classical conditioning paradigm; an associa-
tion between playing tennis (CS) and the shooting pain (US) is
made. CSs not only elicit the memory of the US (“during that
tennis game, I had a shooting pain in my back”), but create the
expectancy of the US as well (“if I will play tennis, then I will
experience this pain again”). The relationship of the CS and the
US is both associative (evaluative learning) and predictive (expec-
tancy learning) in nature [46]. Because of the CS–US association,
the thought of playing tennis elicits an avoidance response (con-
ditioned response [CR]). The maintenance of this new behavioral
response can be understood from an instrumental paradigm, since
avoiding tennis is reinforced by avoidance of the negative pain
experience, as well as avoidance of the negative experience of being
fearful of a situation leading to pain. However, there is evidence
that avoidance responses paradoxically increase the threat value
of the US, rather than diminishing it [47].
In summary, the anticipation of pain engages similar defen-
sive responses to those that occur following actual exposure to
a painful stimulus. In chronic pain, defensive behaviors are the
result of the learning of propositional (if…, then…) knowledge
about the association between stimuli and the reinforcement of
avoidance/escape behavior, and they may be less adaptive since
they are likely to maintain fear levels.
Three ways to acquire pain-related fear
There are three ways in which propositional knowledge about the
relationship between stimuli and pain can be acquired, and by
which behavior is determined. The former example about the tennis
player is an example of learning by direct experience; the person
actually experiences the CS–US relation and his response (avoid-
ance of playing tennis) is reinforced by no longer experiencing pain
and fear.
Research findings suggest that fear learning in chronic pain
patients also occurs through verbal threat information. Besides
illness information that a person gathers from the social environ-
ment, media sources, such as the internet or television, can provide
threatening information. Healthcare providers can also uninten-
tionally be a source of threatening information in the diagnostic
phase and during treatment. Most chronic pain patients with
pain-related fear appear to base their conviction about vulner-
ability to (re-)injury on the results of diagnostic tests. Diagnostic
information might be interpreted as being more threatening than
intended by the medical specialist [48]. Patients contact several
healthcare providers in their continuing search for effective treat-
ment. The different beliefs and orientations of these providers can
play a role in the patient’s complaints [49,50]. Healthcare providers
often tell patients not to perform certain activities or movements.
For example, a patient with whiplash-associated disorder is told
not to work above shoulder-height. This process is referred to as
rule-governed learning; the verbal transmitted rule of the therapist
may govern the patient’s behavior, who did not actually experience
the negative consequences by himself. Healthcare providers’ advice
for chronic pain patients may vary substantially. A biomedically
orientated healthcare provider may suggest that all pain-inducing
activities should be avoided, thereby suggesting a strong CS–US
association between activities and damage [51]. On the contrary,
healthcare providers holding a more biopsychosocial orientation
may recommend high levels of activity despite continued pain,
suggesting no relationship between activities and harm [49,50]. In
a study by Bishop et al., the attitudes and beliefs of healthcare
providers were associated with their advice about return to work.
Nearly 30% of the respondents would advise a described patient to
stay off work, contrary to the UK guideline. This advice correlated
with a biomedical approach of the healthcare provider, opposed to
a more behavioral orientation [52].
Olsson and Phelps describe an experiment in which they found
evidence for observational learning or modeling of the associa-
tion between pain and fear. They directly compared three path-
ways to fear and found that CSs acquired their threat value (US)
through being paired with a painful shock (direct experience),
with observed fear expression in another person (observational
learning) or with the experimenter’s verbal instructions (learn-
ing by verbal threat information). Fear responses to the CS were
of comparable magnitude after the three kinds of learning [53].
Likewise, Helsen et al. showed that healthy subjects can acquire
pain-related fear (CR) by observing a human model performing
a cold pressor task, in which the color of the water (orange or
pink water serving as CS+ or CS-) indicated the US: the models
facial expression showing either pain (negative US) or relaxation
(positive US). When tested themselves, the subjects’ fear and
pain scores show that they learned the CS–US associations they
previously observed in the model, despite equal temperatures of
both orange and pink cold pressors.
In summary, pain-related fear in patients with chronic pain can
be a learned, conditioned response that can be acquired through
at least three pathways. One of the difficulties is that through
learning, individuals can remain engaged in defensive behaviors,
even when the source of threat has diminished. In the next section,
ways to assess pain-related fear will be summarized.
Assessment of pain-related fear
Different methods can be used to assess pain-related fear.
Questionnaires may help to specify the characteristics of the US;
for example, what is the content of the patient’s fear (e.g., harm,
[re-]injury, increasing pain, losing a job or losing independence)?
Pictorial stimuli of movements and activities can be used to assess
the different fear-eliciting stimuli (CSs) and the level of fear
that these stimuli elicit. The interview aims to gather informa-
tion about the whole chronic pain problem and the associations
between the different aspects.
Questionnaires
A frequently used questionnaire is the Fear Avoidance Beliefs
Questionnaire (FABQ) to assess beliefs about how work and physi-
cal activities affect low back pain [54]. The Pain Anxiety Symptom
Scale (PASS) measures cognitive anxiety symptoms, escape and
avoidance responses, fearful appraisals of pain and physiologic anxi-
ety symptoms related to pain [55]. To evaluate fear of (re-)injury due
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to movement, the Tampa Scale for Kinesiophobia (TSK) can be
used [56,57]. All three questionnaires have proven to be reliable and
valid (FABQ [54,58], PASS [59] and TSK [60,61]). For clinical purposes,
questionnaires seem to be appropriate as a first screening, but they
are not sufficient to tell the exact nature of the perceived threat.
Pictorial presentation of fear-evoking stimuli
A limitation of the aforementioned questionnaires is that these
questionnaires do not provide information about which specific
movements and activities (CSs) the patient fears or avoids [62]. For
the purpose of this, sets of pictures were designed, each showing a
person performing a specific movement or activity. The pictorial
sets can be used to determine the overall severity of fear of move-
ment, as well as to guide treatment by constructing a fear hierarchy.
To assess fear in patients with low back pain, the Photograph Series
of Daily Activities (PHODA) is appropriate. A short electronic
version is freely available [201]. The Pictorial Fear of Activity Scale-
Cervical (PFActS-C) is designed to assess fear in patients with cer-
vical pain [63]. In both sets, patients have to organize photographs
of various daily activities (PHODA) or movements (PFActS-C)
in ascending order, based on the extent to which they believe that
performing these activities would be harmful. By doing so, a per-
sonal hierarchy of fear-eliciting activities can be established, which
can also be used to guide exposure-based treatment. Both sets
have shown good test–retest reliability, stability over time, internal
consistency and construct validity [62,63].
Interview
A semi-structured interview can be used to obtain additional
information about the cognitive, behavioral and psychophysi-
ological aspects of the patient’s chronic pain, with the aim to
estimate the role of pain-related fear in the maintenance of the
problem. The interview may help to gather information about the
patient’s propositional knowledge and assumptions regarding the
relationship between physical activities, pain and (re-)injury. For
example, “if I worked for a whole day, I would be over-using my
back resulting in more pain and, finally, damage” [64].
In conclusion, different instruments can help to gather informa-
tion about pain-related fear. A point of weakness is that most of
them rely on self-report. A start has been made in the development
of implicit measures [65]. In the next paragraph, we will highlight
the research on extinction. This is important before treatments
of pain-related fear are discussed, since the treatment of fear has
its laboratory analog in extinction studies of conditioned fear [46].
Extinction of pain-related fear
Extinction is the reduction of conditioned fear responses as a
result of repeated exposure to the CS, in the absence of the US. In
pain-related fear, this implicates patients being exposed to move-
ments and activities without the feared consequences in terms of
pain, harm or (re-)injury. Knowledge of the circumstances that
facilitate or hamper extinction learning may help to sharpen treat-
ments for pain-related fear in such a way that treatment outcome
can be maximized in the short-term (therapy efficacy), as well as
in the long-term (relapse prevention) [45].
Generally, there is a marked asymmetry between the ease by
which acquisition of fear occurs, compared with the difficulty
by which extinction takes place. For example, learning that
bending the back results in a shooting pain, and experiencing
thoughts about being handicapped or being in a wheelchair, can
be established with only one experience/exposure to this CS–US
association. Extinction of this association has shown to be more
difficult. It is not so easy to understand what is learned during
exposure. Previously, extinction was conceived as unlearning or
forgetting the association between CS and US, due to presenting
the CS (movement or activity) without the US (the catastrophic
representation of pain), resulting in a decrease of fear responses
(the CR) upon the presentation of the CS. There is now a growing
consensus that extinction does not result in simple unlearning or
forgetting the association between CS and US [66]. Rather, there
is evidence demonstrating that a new form of learning occurs that
modifies the CS–US contingency in such a way that the CS no
longer signals an aversive event, and thereby inhibits the expres-
sion of the fear response. Exposure to the CS without US creates
an exception to the rule and competes with the previously learned
knowledge, namely that the US follows the CS [67]. With extinc-
tion, the CS becomes an ambiguous stimulus. Exposure results in
a form of acquired inhibition that suppresses a fear response [68].
Extinction can also be viewed as additional learning that
in a particular context the CS–US association does not exist.
Therefore, it is very difficult to generalize the extinction of fear
to other dissimilar contexts, making relapse likely to occur [69,70].
Phenomena such as spontaneous recovery, reinstatement, renewal
and rapid reacquisition show that the formerly learned association
is still a weak spot after successful extinction.
Interventions to reduce pain-related fear
Once the pain-related fear has been thoroughly assessed, treat-
ment aims to restore functional levels by lowering pain-related
fear. Since there are three ways to acquire pain-related fear, it can
be argued that reducing fear should address the same three ways.
Pain-related fear could be reduced by giving verbal information
(often referred to as education), by observational learning (model-
ing) and by direct experience with fear reduction (exposure) and
correcting catastrophic misinterpretations (exposure with behav-
ioral experiments). All interventions aim at facilitating inhibitory
learning; the previous assumption that activities are harmful and
dangerous is overruled by the new one that activities do not cause
damage (even though pain can occur).
Reducing fear by giving verbal information
Patients who are convinced that certain movements will harm
their body will be reluctant to immediately start falsifying their
basic assumptions about the sequence movement–pain–injury. By
giving verbal information about these relations, the threatening
value of the US is aimed to decrease.
In exposure-based protocols, an educational session is usually
included during which the therapist provides verbal information
about misconceptions regarding the association between move-
ment, pain and harm. The aim of this session is to make a patient
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view their pain as a common condition that can be self-managed,
rather than as a serious disease or a condition that needs protec-
tion. The difference between acute and chronic pain is explained
first. It is explained to the patient that the meaning of pain in
an acute situation can be body damage, but that the pain signal
becomes a ‘false alarm’ in chronic pain. Understanding that the
message is false can enhance the patient’s ability to be exposed to
painful behaviors during treatment. Each patient is given a care-
ful explanation of the fear-avoidance model, using the patient’s
individual complaints, beliefs and behaviors to illustrate how
vicious circles (pain > catastrophic thoughts > fear > avoidance >
disability > pain) maintain the pain problem [64,71,72]. This helps
the patient to understand that the consequences of pain are cata-
strophically overestimated. Education is the first step to enhance
the commitment of the patient to engage in feared activities dur-
ing the actual exposure in vivo. In a study using daily measures,
results demonstrated that education reduces pain-related fear
and catastrophizing, with ongoing improvement when expo-
sure in vivo started. Education alone was not enough to change
behavior: performance of relevant daily activities was not affected
by the educational session and improved significantly only with
exposure in vivo [73].
Another field of research has focused on preventing chronic-
ity of low back pain by giving adequate written information.
Burton et al. studied the impact of an educational booklet on
the beliefs and functional outcome of patients seeking primary
care for an acute or recurrent episode of low back pain. Patients
receiving this biopsychosocially oriented booklet showed signifi-
cantly more positive beliefs about activities and consequences of
low back pain. This positive effect was maintained over a 1-year
follow-up period. This group also showed a tendency to become
less disabled then the group who received information that was
biomedically oriented [74]. In another study, the experimental
group was enrolled in a self-care program. This program con-
sisted of two group sessions and an individual meeting with the
psychologist leading the program in which a plan was made to
enhance self-care and problem-solving related to back pain. One
follow-up phone call was made to evaluate the progress of this
plan. Additional information was given by videos and a book,
both emphasizing the importance of resuming daily life activi-
ties. Controls only received a book about usual back pain care.
The repeated verbal information in the experimental group led
to decreased pain-related fear, and to a lesser extent, to reduced
pain intensity and daily life interference, although a substantial
part remained to have back problems at 6 months follow-up [75].
This is in line with the abovementioned findings in a chronic
pain population [73], where a verbal intervention was found to be
effective in lowering pain-related fear, but actual experience was
needed to change patients’ behavior.
Reducing pain-related fear with observational
learning (modeling)
Congruent with the scarcity in research regarding observational
learning in acquiring pain-related fear, no studies have sys-
tematically evaluated the effect of modeling in order to reduce
pain-related fear. Protocols for graded exposure often suggest that
before the patient is invited to perform a feared activity, the thera-
pist ‘models’ it first [72]. A related study by Colloca and Benedetti
investigated whether placebo analgesia could be induced by social
observational learning. Individuals learned by observing the anal-
gesic experience of others, through a direct conditioning proce-
dure or by verbal information. Interestingly, the magnitudes of
the placebo effects of the social learning condition were similar
to the magnitudes in the group that learned by direct experience.
For learning by verbal information, smaller effects were found [76].
Reducing pain-related fear by experiencing the absence
of the expected threat
For fearful patients it is far more convincing to actually expe-
rience themselves behaving differently than any rational argu-
ments that could be given. The fear hierarchy established with
the PHODA [62] or PFActSv [63] has been used to gradually expose
patients to more threatening activities. This exposure is person-
ally tailored to the functional goals the patient has formulated.
Patients are encouraged to engage in the fearful activity as much
as possible until anxiety levels have decreased. If so, the patient
chooses the next activity from the fear hierarchy, and this is
repeated until even the most highly scored activities from the
hierarchy can be performed.
Additional behavioral experiments give patients an opportunity
to challenge the validity of their catastrophic assumptions. In a
behavioral experiment, the patient is challenged to systematically
test whether the anticipated threat during exposure to a CS is
overestimated or not. Subsequently, a feared activity or move-
ment (CS) is performed until disconfirmation of harm beliefs
for this specific activity or movement has occurred (no US), with
fear reduction as a consequence (lower CR). In clinical practice,
behavioral experiments are hard to separate from exposure, and
they can best be used simultaneously. By conducting hypotheses
about the expected harmful consequences (US) of movements
and activities (CS) the patient receives the opportunity to evalu-
ate catastrophic beliefs [68]. Hypotheses are assumptions taking
the form of “If…, then…” statements (e.g., “If I carry a bag with
groceries, then nerves in my wrist will get blocked and I will have
to let go of the bag”) and are empirically tested during a behavioral
experiment. Treatment is considered to be successful if the patient
no longer avoids activities, indicating that the CS (activity or
movement) no longer signals the US (catastrophes associated with
experiencing pain) and the CR (fear) is decreased. To enhance
generalization and maintain exposure effects over time, exposure
is provided to the full spectrum of contexts and natural settings
in which fear has been experienced. The stimuli are varied; for
example, walking can be done indoors and outdoors, on grass,
sand or on the street, uphill as well as downhill, quickly and
slowly, and so on [72].
Effectiveness of interventions aimed at reducing
pain-related fear
In a narrative review on fear-reducing techniques, Lohnberg
concludes that graded exposure in vivo (GEXP) appears to be
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the most effective treatment for chronic pain in individuals with
increased fear and avoidance, based on the early single case studies
[73,77–82]. A more recent review on treatments available to address
fear-avoidance beliefs in patients with chronic musculoskeletal
pain suggests that GEXP and acceptance and commitment ther-
apy (ACT) result in the best outcomes for treating fear-avoidance
beliefs [83]. A systematic review included four trials that compared
graded activity to GEXP and two trials that compared GEXP to
a waiting list or usual care [84]. The authors conclude that GEXP
is as effective as minimal treatment or graded activity in reduc-
ing pain and disability for persistent low back pain. Effects on
pain-related fear were not reported in this review, and the authors
estimate that the small number and quality of trials do not allow
a good comparison to be made [84].
So far, the published randomized controlled trials on the effec-
tiveness of GEXP in chronic low back pain found mixed results.
Woods and Asmundson randomly assigned 44 patients to GEXP,
graded activity or a waiting list condition. They found that, in
comparison with the graded activity condition, patients in the
GEXP condition demonstrated significantly larger improvements
on measures of fear of pain/movement, fear avoidance beliefs and
pain-related anxiety, but only trend differences for pain-related
disability and pain self-efficacy. When GEXP was compared
with the waiting list control group, GEXP showed significantly
greater improvements on measures of fear-avoidance beliefs, fear of
pain/movement, pain-related anxiety, pain catastrophizing, pain
experience, anxiety and depression. Over a 3-month follow-up,
the GEXP condition maintained improvements [85].
Linton et al. randomized 46 participants into a GEXP plus
usual treatment or waiting list control plus usual treatment group.
After the waiting period, the control group crossed over and
received GEXP. The exposure group scored better on function,
but not on fear or on pain, and the effect sizes were modest. When
the control group crossed over to treatment, significant treatment
effects were noted for fear and function. Compared to a group
receiving usual treatment and waiting for exposure, GEXP dem-
onstrated a significantly larger improvement on function. Overall,
GEXP had moderate effects on function, fear and pain intensity.
The authors conclude that GEXP may be important in treatment,
but that it is not recommended as a standalone intervention that
is added to usual care [86].
A multicenter trial included 85 patients in either a GEXP or
a graded activity program [87]. It was demonstrated that GEXP,
despite excelling in diminishing pain catastrophizing and per-
ceived harmfulness of activities, was equally effective as graded
activity in improving functional disability and main complaints,
although the group difference almost reached statistical signifi-
cance favoring exposure. Treatment conditions did not differ in
changing pain intensity and daily activity levels, nor was GEXP
superior to graded activity in the subgroup of highly fearful
patients. Irrespective of treatment, approximately half of the
patients reported clinically relevant improvements in main com-
plaints and functional disability, although for the latter outcome
the group difference was almost significant favoring GEXP. This
study demonstrates that up to 6 months after treatment exposure
is an effective treatment, but not more effective than graded activ-
ity, in moderately to highly fearful patients, although its superi-
ority in altering pain catastrophizing and perceived harmfulness
of activities is clearly established [87]. An interesting additional
finding of this study is that the differential effects of both treat-
ments on disability are mediated by changes in the perceived
harmfulness of physical activities.
All the abovementioned studies have included patients with
chronic low back pain. Single case studies have demonstrated
that GEXP can also be successfully applied to other chronic
pain conditions, such as complex regional pain syndrome type I
(CRPS-I; [71]), post-traumatic neck pain [88] and vaginismus [89].
Expert commentary
Pain-related fear as a predictor of future disability
While it is well established that pain-related fear is a maintaining
factor once chronic pain has developed, more caution is needed
with regard to the role of pain-related fear in the transition of acute
pain to the chronic stage. Although it is suggested that pain-related
fear is a potential risk factor for the inception of chronic pain and
even a potential vulnerability factor for the inception of acute
pain in pain-free individuals [18], some studies raise doubt about
this (e.g., [18,22,90]) and call for more longitudinal investigation.
Given that aversive stimuli may activate a network of fear processes
simultaneously, and given the bidirectional relationship between
safety behaviors and threat appraisals, a different methodology,
such as path analytic analyses, is needed [27].
Working mechanisms of different treatments for
chronic pain
Other techniques that are not primarily aimed at reducing pain-
related fear have been shown to have a fear-reducing effect as well.
This has been the case for physical therapy (e.g., aerobic and mus-
cle strength training) [91], graded activity [84,87] and ACT [92–94].
It has been argued that the working mechanism behind these
techniques is also the reduction of perceived threat [95]. Different
cognitive techniques or strategies that could serve to enhance the
effects of exposure therapy have been proposed. For example,
acceptance strategies have received increasing attention and are
starting to establish a small evidence base. In a randomized con-
trolled trial, the effectiveness of exposure and acceptance strate-
gies was compared with a multidisciplinary treatment program to
improve functioning and quality of life in longstanding pediatric
pain [96]. Results were in favor of the ACT. These results are in line
with a previous study in which a group of 21 chronic pain patients
and patients with whiplash-associated disorders who received
treatment emphasizing exposure and acceptance strategies showed
more improvement than a waiting list group with regard to pain
disability, life satisfaction, fear of movements, depression and
psychological inflexibility [94]. Linton recently described a case
study in which dialectical behavioral therapy (DBT) is applied
to a patient with a complex persistent pain, depression and dis-
ability syndrome. DBT is a technique that relies on training of
emotional regulation, which supports acceptance of the patient
and their behavior without judgment, while at the same time
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working on the things that can change or improve [97]. The inter-
vention program lasted approximately 6 months and consisted
of 16 sessions in which different intervention techniques were
used: validation and education, interoceptive exposure (including
focusing on inner physiological feelings in a nonjudgmental way),
savoring, emotional regulation (including identifying thoughts
and feelings in a nonjudgmental manner), dialectical behavioral
experiments, activity monitoring and a maintenance program.
The patient made considerable progress, both on self-report mea-
sures and objective measures, and despite the presence of some
pain, sleeping problems and emotional discomfort, the patient
was able to function on a more satisfying level [97]. The effective
component in this case remains unsure, but Linton argues that
the emotional focus might have helped the patient to fully engage
in the exposure [97].
It would be worthwhile to compare these treatments to address
the question “what works for whom?” Although these treatments
differ in their treatment goals, in enabling the patient to live
a valued life (ACT) and reducing pain-related fear (GEXP)
respectively, the commonality is that both treatments encourage
patients to take part in daily life activities. The question remains
whether treatment necessarily has to work through fear reduction
or that, by acceptance of fear, the same improvements in enhanc-
ing daily functioning and quality of life can be established. As
long as this question is not answered, in our opinion it would
be a missed opportunity not to give clients a chance to modify
their dysfunctional beliefs. The effectiveness of GEXP on pain-
reduction might be explained by an increase in the acceptance
of pain. Exposure to previously avoided situations is considered
to be the core intervention, emphasizing acceptance of what can
not be directly changed (thoughts, emotions and bodily sensa-
tions) as a way of engaging in activities that are meaningful, but
possibly painful or fear provoking [94,98]. It would be interesting
in future GEXP studies to determine to what extent the results
are not mediated by a change in acceptance and commitment.
Related to discussion about acceptance is the issue of relatively
high drop-out rates in GEXP. In the review from Bailey et al.,
nine studies on GEXP included 246 participants, of whom 96
(39%) dropped out. In ACT, the drop-out rate was 28.5% and
in mixed cognitive–behavioral therapy protocols it was 15% [83].
A possible explanation of the high drop-out rate of GEXP can
be found in that exposure to feared activities similarly implies
exposure to painful activities, which might not be acceptable for
all patients. It would be interesting to study whether this subgroup
could benefit from additional acceptance strategies.
Extinction of pain-related fear by verbal instruction
& modeling
Existing treatments to reduce pain-related fear seem to rely domi-
nantly on learning by direct experience using exposure in vivo
techniques. Less is known about how pain-related fear can be
decreased using verbal information, and the existing research
is limited to using booklets in primary care settings. Likewise,
the observational learning on extinction of pain-related fear in
chronic pain patients has not yet been studied. Since both Olsson
and Phelps and Colloca and Benedetti demonstrated that the
learning curves for observational learning were of the same mag-
nitude as learning by direct experience, it might be worthwhile
to examine whether verbal instruction and observational learn-
ing could produce or enhance fear reduction during exposure
in vivo treatment [53,76,99]. Although current exposure protocols
advocate verbal instruction and the modeling role of the therapist,
their effects have not been systematically studied yet. This issue
also revives a discussion about whether exposure-based treatment
could be delivered as a group program [100]. Conceivably, seeing a
group member perform a feared activity is more valid than seeing
the therapist modeling the activity, despite the evident disadvan-
tage that it will be more difficult for the therapist to monitor
idiosyncratic safety-seeking behaviors in each individual patient.
A related issue that is raised by several authors [84,101] is who should
deliver exposure-based interventions? An important difference
from most anxiety problems is that pain-related fear is treated not
in mental health services, but in a multidisciplinary rehabilitation
center. This implies that they see other disciplines, such as physi-
cal or occupational therapists and nurses, delivering exposure-
based treatments. The question of whether a nonpsychologist can
deliver a psychological intervention for pain-related fear has not
been studied yet; however, this is warranted since it might have
a major effect on the success of treatment and cost–effectiveness.
Return of fear after successful extinction
Exposure in vivo therapy is widely and successfully applied to
reduce pain-related fear and pain-related disability, but patients
and therapists alike keep struggling with problems of relapse
and prematurely ending treatment. Extinction, the laboratory
analog of exposure, is viewed as a process that establishes new
inhibitory associations, rather than the type of ‘unlearning’ of
previously established associations [46]. Relapse after an extinction
procedure, such as exposure, could be explained by insufficient
generalization of what has been learned in therapy – that is, dis-
confirming beliefs, to other situations and contexts. Response
generalization is hindered by the competition of the original
meaning of the stimuli and the new meaning learned during
exposure [102]. Several studies have investigated generalization of
exposure to movements in a laboratory setting, and reveal that
repeated exposure to the same or different movements does not
necessarily generalize to a new movement, suggesting that the
corrective impact of exposure in vivo may be limited [67,103,104].
Only one study demonstrated successful generalization of pain
expectancy corrections across four reaching tasks of increasing
intensity in chronic low back pain patients reporting high levels
of pain-related fear [105]. In the aforementioned experimental stud-
ies, subjects are exposed to movements in an artificial environ-
ment, with little ecological validity, only several times in a short
timespan. To what extent this is comparable to GEXP treatment,
where a patient is repeatedly exposed to fearful daily life activities
over a longer period of time, remains open for future research.
Current treatment mainly takes place in the artificial context
of a hospital or rehabilitation center, it would be interesting to
study which entities (repetition, movement vs activity, timespan,
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context) enhance generalization to optimize treatment effect in
both results and costs. In the study by Linton et al., the authors
describe that patients were exposed to activities that were within
‘normal’ limits [86]. It would be interesting to study whether pain-
related fear can be diminished by exposing patients only to regular
daily life activities, or if patients would benefit in the long-term
from exposure to their most highly feared activities.
Safety-seeking behavior & safety signals: protection from
extinction?
Contradicting opinions exist regarding the use of safety-seeking
behavior during exposure. Some authors advocate a judicious use
to make the start of exposure less aversive [106]. Others advocate
that safety-seeking behaviors should be minimized during expo-
sure therapy because of their maintaining effect on anxiety-gen-
erating beliefs, and that patients should be given a clear cognitive
rationale for doing so [47,107]. Illustrative of safety-seeking behavior
is the research in claustrophobia that suggests it is not the actual
use of safety behavior that interferes with fear reduction, but that
the perception of their availability is disruptive [108]. This study
found that safety aids do not need to be actually used in order
to exert their detrimental effects, consistent with countless clini-
cal observations of patients carrying rescue pain medication or
other safety aids without actually using them. Safety signals are
stimuli that indicate that an aversive outcome is highly unlikely.
A patient may learn that bending over does not hurt their back,
but only in the presence of the safety signal, such as the therapist.
In the absence of the therapist, the previously learned rule that
movement can hurt the back can be activated again.
There is considerable evidence that a return of fear might be
due to the presence of concurrent safety signals or safety-seeking
behavior during the extinction procedure [45,109,110]. The most
commonly accepted theoretical explanation for this effect is pro-
tection from extinction, which posits that patients attribute the
absence of the feared outcome to the safety signal or to their safety
behavior, and thus fail to update their threat beliefs. Protection
from extinction has been demonstrated in a study during which
stimulus A is associated with the presence of a threatening US,
whereas stimulus B signals the absence of the US. The presence of
the inhibitory cue B during extinction of stimulus A cancels out
the expectancy of the US, causing no more discrepancy between
what is expected (nothing) and what actually happens (nothing),
thus leaving threat beliefs intact [47,111]. Protection from extinc-
tion has been demonstrated when an external stimulus was used
as a safety signal [111] and when avoidance was used as safety-
seeking behavior [47]. Consequently, clinicians using exposure
treatments should assist the patient in identifying threat-relevant
safety strategies and encourage them to not only discard their use
(safety-seeking behavior; e.g., not using a protective splint during
exposure), but also their availability (safety signal; e.g., carrying
the splint in one’s purse).
Fear reduction or optimizing inhibitory learning?
There is some evidence suggesting that exposure in patients who
catastrophize about pain is less successful compared with exposure
in low catastrophizers [112]. One possible mechanism is that high
pain catastrophizers have more difficulty in inhibiting their defen-
sive responses [113]. Indeed, Craske et al. conclude that fear reduc-
tion should not be the goal of exposure, but optimizing inhibitory
learning. Reductions in fear and physiological arousal are not
indicative of corrective learning. Since extinction is no longer seen
as unlearning, but as learning a new rule that co-exists with the
old rule, the context determines which rule is valid. Treatment
should be aimed at enhancing retrievability of the newly learned
associations in different contexts and at different times [114]. The
examination of this assumption in the reduction of pain-related
fear is warranted.
Five-year view
Recent developments in the field of acquisition and extinction
of fear and anxiety in general may inspire new research avenues
in the field of pain-related fear, in particular with regard to the
effectiveness and efficiency of current treatment strategies.
Exteroceptive versus interoceptive exposure
Graded exposure in pain-related fear has focused on the learned
association between activities and predicted pain and harm.
Recent ideas focus on the fact that not only movements, activities
and actions can serve as CSs. Internal sensations in the body can
have predictive value as well [De Peuter S, Van Diest I, Vansteenwegen D,
van den Bergh O, Vlaeyen JW. Pain-related fear and chronic pain: interocep-
tive fear conditioning as a novel approach. Manuscript submitted]. For
example, mild pain or a specific body position (CS) can become a
predictor for intense pain (US). Interoceptive conditioning is seen
as more resistant to extinction than extinction of exteroceptive
conditioning [115], providing new challenges in future research and
treatment. A recent study compared interoceptive exposure with
distraction/relaxation in six individuals with chronic back pain
with regard to the reduction of threat value of pain [116]. Results
demonstrated a general trend towards reduced pain-related dis-
tress, even after a 3-month follow-up period. Even though these
interventions only encompassed a single type of intervention, both
techniques were about equally effective in reducing pain-related
distress [116].
An affective–motivational approach
A number of authors have recently called for an expanded affec-
tive–motivational approach, with a prominent focus on behavior
in the context of multiple goals [117,118]. In their attempt to resume
daily life activities, pain patients engage in several goals, some of
which are directly related to dealing with pain, whereas others are
not pain-related. These multiple goals may facilitate each other,
or they can be conflicting. For example, the goal to satisfy others
by resuming work-related activities may conflict with the goal to
protect bodily integrity by staying home. Unfortunately, unre-
solved pain-related goal conflicts may fuel fear [119]. An emerging
and intriguing question is whether cognitive–behavioral therapies
aimed at the re-evaluation of major life goals and at the resolu-
tion of enduring goal conflicts help to counter fear-driven and
disabling avoidance behavior [117,118]. An illustration of such a
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motivational approach is provided by Christiansen and colleagues
who evaluated a brief goal-pursuit intervention to improve physi-
cal capacity through exercising in chronic back pain patients [120].
In order to facilitate the realization of intended goals, the follow-
ing strategies were utilized:
•? Mental contrasting to increase the patient’s expectations about
achieving the promoted goal;
•? Problem-solving techniques to help the patient to overcome
obstacles associated with exercising;
•? Implementation intentions to help the patient to prioritize the
intended goal in future conflict situations.
This intervention led to greater improvements in physical capacity
compared with the treatment as usual. It would be worthwhile
to examine whether the effects of fear-reduction treatments can
be enhanced by adding a motivational component focused at the
resolution of goal conflicts [121].
Financial & competing interests disclosure
The contribution of Mariëlle Goossens was supported by ZonMw, program
Rehabilitation Research, Grant No. 60-60500-98015. Participation of
Johan WS Vlaeyen was supported by the NWO Social Science Research
Council of the Netherlands, VICI Grant No. 453-04-003, and an Odysseus
Grant by the Fund for Scientific Research – Flanders, Belgium (FWO). The
authors have no other relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart from
the disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
• Fear avoidance models explain that pain perception can be catastrophically interpreted, resulting in a state of fear that makes a patient
hypervigilant for signs of threat and evokes avoidance behavior. Negative consequences of this behavior are disability and disuse, which
have detrimental long-term effects on the pain experience.
• Dysfunctional pain-related fear arises when neutral stimuli (movements and activities) become predictors for the occurrence of pain and
associated harm. The learning of this association can be based on direct experience, on observation and on receiving
threatening information.
• Questionnaires (Tampa Scale for Kinesiophobia, Fear Avoidance Beliefs Questionnaire, Pain Anxiety Symptom Scale), as well as pictorial
sets (Photograph Series of Daily Activities, Pictorial Fear of Activity Scale–Cervical), are available to specify the nature of pain-related
threat. A semi-structured interview may be considered to gain insight into additional aspects of the chronic pain problem.
• Extinction is the reduction of conditioned fear responses as a result of repeated exposure to the conditioned stimulus (CS) in absence of
the unconditioned stimulus (US). Inhibitory learning results in a changed CS–US relationship; the CS becomes an ambiguous stimulus
for which the context determines a positive or negative outcome.
• Treatments for pain-related fear have mainly focused on written or verbal information regarding the paradoxical effects of avoidance
and escape behaviors. Recently, exposure-based treatments have been developed during which patients engage in fearful activities to
disconfirm threat beliefs and reduce fear. The role of observational learning during treatment warrants further study.
• Protection from extinction is a phenomenon that explains how both context features and behavior can leave a CS–US relation intact
during exposure; patients attribute the absence of the feared outcome to safety signals or to their own safety behaviors, and fail to
correct catastrophic interpretations.
• Graded exposure in vivo seems the treatment of choice for reducing pain-related fear. Further evidence is needed regarding the change
in pain and disability and the exact working mechanism of exposure treatment.
• Future directions in the field of pain-related fear will study how internal cues can serve as CSs, and how this will affect treatment.
Studies that examine whether the effects of exposure can be magnified when adding a motivational component, during which patients
are coached in managing their goal-conflicts.
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Fear reduction in patients with chronic pain: a learning theory perspective