Topical Review
Uncertainty in a context of pain: disliked but also
more painful?
Jonas Zamana,*, Lukas Van Oudenhoveb,c, Johan W.S. Vlaeyena,d
1. Introduction
Pain is part of a motivational system that urges the individual to take
action when the integrity of the body is challenged.37 Although
regularly updated information available from the internal and external
environment is used to estimate the risk for such bodily threat, this
process is fraught with uncertainties. Indeed, patients may dwell on
the cause of their pain, its meaning, their future, when the next pain
episode will occur, the intensity of their pain, or how to control it.8
Uncertainty denotes “a lack of sureness about someone or something
and may range from a falling short of certainty to an almost complete
lack of conviction or knowledge, especially about an outcome or
result” (Merriam-Webster.com Dictionary, s.v. “uncertainty,” accessed
July 15, 2020, https://www.merriam-webster.com/dictionary/uncer-
tainty). Many different situations may give rise to uncertainty, of which
unpredictability and uncontrollability are the most pertinent.23 When
living with pain, uncertainty can emerge at different levels and through
different origins that can affect the experience and impact of chronic
pain.23 For instance, patients with pain might experience high levels of
uncertainty because of the ambiguity of their pain (eg, is it a sign of a
life-threatening condition or not?), because of an inability to explain its
origin (ie, lack of knowledge), or because of conflicting treatment
information (ie, inconsistency, rest vs keep on moving). In clinical
studies, uncertainty has been related to various negative behavioral
outcomes.18–20,28,35 It is often suggested that uncertainty also
aggravates pain perception, yet endeavors to investigate the relation-
ship between uncertainty and pain perception in experimental settings
have yielded mixed findings. This article aims to summarize research
on this matter in an attempt to identify potential methodological and
conceptual challenges to inspire future research.
2. Unpredictability
Uncertainty is a broad concept that transcends a single source of
origin. Nevertheless, endeavors to investigate its effect on pain
Sponsorships or competing interests that may be relevant to content are disclosed
at the end of this article.
a
Health Psychology, Faculty of Psychology and Educational Sciences, KU Leuven,
Leuven, Belgium, b Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational
Research Centre for Gastrointestinal Disorders (TARGID), Department of Chronic
Diseases, Metabolism, and Ageing, KU Leuven, Leuven, Belgium, c Consultation-
Liaison Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium,
d
Department of Clinical Psychological Science, Maastricht University, Maastricht,
the Netherlands
*Corresponding author. Address: Health Psychology, Faculty of Psychology and
Educational Sciences, KU Leuven, Tiensestraat 102, 3080 Leuven, Belgium. Tel.:
132 16 37 31 97; fax: 132 16 3 26144. E-mail address: jonas.zaman@kuleuven.be
(J. Zaman).
PAIN 162 (2021) 995–998
© 2020 International Association for the Study of Pain
http://dx.doi.org/10.1097/j.pain.0000000000002106
April 2021
· Volume 162
· Number 4
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
perception have often reduced it to the issue of unpredictability. It
is well known that both humans and animals have a strong
preference for situations that enable them to predict aversive
events,3,25 and that the inability to do so can have an extensive
impact on an emotional, behavioral, and motivational
level.1,10,22,25,27 Unpredictable pain can result in increased
stress, a general state of arousal, and sustained levels of
anxiety.15,34 In an attempt to refine the concept of anxiety, Imada
and Nageishi17 proposed 9 different manipulations to alter
uncertainty (Table 1), some of which can be grouped into 2
classes as proposed by Miller: those that foster prediction
accuracy about the exact moment of occurrence (called onset
predictability) and those that manipulate information about the
characteristics of the aversive stimulus, such as its location,
duration, or intensity (termed event predictability).25
3. Uncertainty in a Bayesian framework
Efforts to investigate the effects of uncertainty on pain perception
predominantly used a dichotomous approach comparing pain
ratings between predictable and unpredictable conditions. The
assumption in those studies is that the compared conditions differ
only in terms of uncertainty levels. However, as we will argue, this is
often not the case, especially for studies that relied on manipulations
of event predictability. Before elaborating hereupon, we first
introduce the concept of perception as a Bayesian process.16,30
Here, perception is considered the active inference of sensory input
based on prior beliefs (Fig. 1). Specific sensory inputs are more likely
than others for a given physical stimulus, resulting in a probability
distribution called the likelihood. Here, the issue of uncertainty is
implemented by assigning different probabilities to a set of possible
stimuli. This probability distribution captures that different stimuli
could have caused the sensory input and that this is more likely for
some stimuli than others. Furthermore, expectations about which
stimuli are more likely are represented by another probability
distribution called the prior. It is the combination of sensory input
(likelihood) with prior information (prior) that drives perception (ie, the
posterior). For example, a high-intensity pain cue will shift the prior to
the expected sensation. When the expectation corresponds with the
sensory input (ie, the prior strongly overlaps with the likelihood), the
perception will become more certain (ie, the posterior becomes
narrower). However, when the expectation does not match the
sensory input, the perception will shift in the direction of the prior
(Fig. 1).
4. The role of expectancies
Prior beliefs do not remain naive and stable because they
incorporate the experience gained across subsequent events,
where the posterior becomes the prior for the next pain episode.
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Table 1 intensity (stimulus A), whereas the unpredictable cue is followed

Taxonomy of manipulations to make a situation uncertain. by stimuli of different pain intensities (stimulus A or B). Depending
on the intensity of stimulus B in the unpredictable condition,
Taxonomy by Imada and Nageishi17 Taxonomy by Miller25
the mean of the prior for the unpredictable cue will be
Signaled vs unsignaled aversive stimuli Onset positioned at a higher (or lower) location compared with the prior
Fixed vs variable temporal intervals Onset for the predictable cue, reflecting differences in acquired
Fixed vs variable stimulus number — expectations (Fig. 1). Next, if a test stimulus is presented that is
below the mean of the prior in the uncertain context, it will be
Fixed vs variable stimulus duration Event
perceived as more intense compared with the certain condition
Fixed vs variable stimulus intensity Event (where the prior and likelihood overlap). The opposite can be
Fixed vs variable cue stimulus interval Onset expected when the test stimulus is located above the prior in the
uncertain context. Hence, depending on which stimulus in-
Fixed vs variable cue intensity —
tensities are used and which stimuli are compared between
Fixed vs variable stimulus quality, pattern, and Event conditions, inferences can be opposite with the apparent
locus conclusion that uncertainty is related to more or less pain or no
Fixed vs variable cue quality, pattern, and locus — difference at all (Fig. 1).
Thus, the contrasted conditions not only differ regarding
uncertainty levels but, more importantly, can also differ on the
acquired expectations. As a consequence of this methodological
Because of this generative updating process, humans do not intertwining of 2 processes, it is impossible to disentangle the
remain naive in most experimental, unpredictable conditions but effects attributed to uncertainty vs those due to differences in
acquire expectations about upcoming pain. That is, the prior will expectations. In other words, the effects of uncertainty on pain
evolve towards a wide distribution reflecting some degree of perception are confounded by expectancies. For instance,
uncertainty with a peak that centers around the mean pain Brown et al.4 included 3 stimulation intensities that were
intensity resulting in a regression-to-the-mean effect.16,30 In preceded by either a cue that correctly signaled the intensity or
several experimental studies, a custom method is to compare a cue that signaled a 33% probability of receiving a low-, a
pain ratings between predictable and unpredictable pain using moderate-, or a high-intensity stimulus. From a Bayesian
cues. The predictable cue reliably signals the same stimulus perspective, the prior of the unpredictable cue is expected to

Figure 1. Perception as a Bayesian inference process: Expectations (the prior) and sensory input (the likelihood) are precision averaged into a percept (the
posterior). Depending on which 2 conditions are compared, conclusions about the role of uncertainty differ. In this theoretical example, the uncertain cue had an
equal probability of being followed by either a low- or a high-noxious stimulus (NSL [upper row] or NSH [lower row]). As a consequence, more pain is expected in the
uncertain condition when a low-noxious stimulus is presented, and less pain is expected when a high-noxious stimulus is presented compared with when both
stimuli are correctly cued. When another stimulus is presented than those used during training (ie, medium-noxious stimulus), again differential effects are
expected depending on whether the uncertain condition is compared with cued low or high pain. Note that in these scenarios, the effects originate because of a
shift in the posterior in both cued (predictable) conditions.

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 April 2021
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be centered around the moderate-intensity stimulus, reflecting
the average of all possible stimuli intensities. The priors for each
predictable cue are expected to be located at the corresponding
stimulus intensities. As a consequence, the expected average
pain level (the mean of the prior) will be (1) higher in the
unpredictable cue compared with the low-intensity cue, (2) similar
to the expected pain level for the moderate-intensity cue, and (3)
lower compared with the high-intensity cue. They found (1) higher
ratings for the non-noxious stimulus when preceded by the 33%
cue compared with the low-intensity cue, (2) equal pain ratings for
the moderate-intensity noxious stimulus between both cues, and
(3) lower pain ratings for the high-intensity noxious stimulus when
preceded by the unpredictable cue.4 Attributing the differential
effects to an aggravating pain effect of uncertainty is difficult,
whereas they can be easily understood from a Bayesian
perspective. In a conditioning experiment by Lin et al., one of 2
cues was always followed by a low-intensity noxious stimulus.
The other cue was followed by either the same stimulus or a high-
intensity noxious stimulus (ratio 50%-50%), which should result in
a prior with a higher mean pain expectancy. They found that the
low-intensity noxious stimulus was perceived as more painful
when uncertainty was high.21 In yet another study, participants
received innocuous and noxious stimuli in a predictable and
unpredictable manner. Higher ratings were found for the noxious
and lower ratings for the innocuous stimulus when their intensity
was predictable.42 Given the precise prior expectations, these
results are in line with the proposed framework. However, other
studies found overall higher pain ratings when stimuli were
presented in blocks of variable compared with fixed intensi-
ties.29,32 In this context, model extensions such as the recent 2-
process model of Press et al. may be especially interesting. Here,
a Bayesian account is combined with a learning process where
prediction errors (determined by the overlap between the prior
and posterior) influence the perception of certain events depend-
ing on its size.31
Within the Bayesian framework, uncertainty regarding future
outcomes is reflected by the width of the prior. The more uncertain
we are about a future event, the wider the prior, and the lower its
influence on the posterior will be. That is, following the principles of
Bayes’ rule, information is combined optimally. Both sensory input
and expectations are precision weighted such that information with
the lowest uncertainty will have the most substantial influence on the
posterior. In the most extreme scenario, a uniform prior exists such
that all events have an equal probability. As a consequence,
perception (the posterior) will be solely determined by the sensory
input (the likelihood). Only a few studies have tried to investigate the
effects of uncertainty by only affecting the width (and not the mean of
the distribution) of the prior. Yoshida et al. attempted to investigate
the effects of uncertainty while ensuring similar average expectations
between conditions using a vicarious learning paradigm in a small
sample (N 5 13).40 Before the stimulus presentation, participants
saw 8 fictitious pain ratings of previous participants as a cover story.
The authors found that high levels of uncertainty (ie, fictitious ratings
with large variation) led to higher pain ratings regardless of in
which direction the vicarious information was manipulated.40
However, a recent study failed to replicate their finding in a larger
sample (N 5 40).41
Another way to induce uncertainty, where differences in
expected pain levels between conditions are less likely to occur,
is to manipulate onset predictability. In those paradigms,
participants have information about the stimulus intensity, but
their ability to predict its onset varies between conditions. The
bulk of onset predictability studies did not found any effect of
unpredictability on pain perception,2,6,7,11–15,33,39 with a few
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
www.painjournalonline.com 997
exceptions.5,9,24 However, in one of those studies, pain ratings
were only obtained in between blocks instead of after each
stimulus presentation, which may have affected intensity
ratings.38 Also, these studies did not control for differences in
anticipation duration, which seems to be an important factor, as
effects of onset predictability disappeared when ensuring similar
periods of pain anticipation between conditions.6 Collectively,
and contrary to the common idea that uncertainty amplifies the
perception of pain, there is currently little experimental evidence
for a direct influence of uncertainty on self-reported pain ratings.
5. Uncertainty is more than unpredictability
Furthermore, as already mentioned, uncertainty cannot be
reduced to unpredictability and encompasses several other
components. For example, patients with chronic pain can differ
not only in the extent to which they perceive pain as unpredictable
but also in how they conceive the origin of their pain. For instance,
a patient with low back pain might have learned that the execution
of a certain movement will trigger pain onset but may lead him to
worry about his future (eg, ability to continue hobbies and
maintenance of job). In other patients, the uncertainty originates
from the absence of clear cues signaling pain increases or the
inability to predict the course and the duration of a pain episode.
However, systematic research on these different aspects is
currently lacking. Furthermore, a conceptual challenge that may
limit the generalizability of experimental work on uncertainty to
real life is the issue of controllability. Persons do not volunteer to
develop a chronic pain state, with little control over their pain or
the ability to escape the situation. Participants in experiments, on
the contrary, volunteer to experience pain, knowing that they can
escape from the situation at any time point (for a review on the
effects of controllability, see Ref. 26). Besides, experimentally
induced pain differs in many more aspects that affect uncertainty
levels compared with the pain in real life. For instance, pain in an
experimental context does not lead to ambiguity over its meaning,
its origin, or its implications. Furthermore, participants receive
explicit information (for ethical reasons) that their pain will be
within the threshold of tolerance and safety, which is not the case
outside of experimental situations.
At this point, it seems that pain uncertainty in experimental
settings does not directly affect pain perception, although there is
evidence that uncertainty aggravates the overall impact of chronic
pain on patients’ lives. Furthermore, researchers should be aware
that certain manipulations of uncertainty can simultaneously
affect expectations that also influence the reported pain in-
tensities. In addition, not only have few studies considered pain
expectancies on whether and how uncertainty impacts pain
reports, the research so far has neglected the influence of
expected vs unexpected uncertainty itself. Based on prior
information, individuals may expect the course of pain to be
uncertain, which may have different consequences as compared
to unexpected uncertainty. The research on such meta-
uncertainty is an emerging field that still has to be explored in
pain science.36 Finally, the relationship between pain uncertainty
(both overall levels and different types) and pain reports, as well as
focus on other outcomes (eg, disability levels and quality of life) in
daily contexts requires further scientific attention, to better
understand how individuals protect themselves against bodily
threat in an uncertain environment.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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J. Zaman et al. 162 (2021) 995–998
Acknowledgments
J. Zaman is a postdoctoral research fellow of the Research
Foundation Flanders (FWO, 12P8619N) and received funding
from the Efic-Grunenthal grant (EGG ID 358254826). The
research was sponsored by the “Asthenes” long-term structural
funding (METH/15/011)—Methusalem grant by the Flemish
Government to J.W.S. Vlaeyen. L. Van Oudenhove is an
associate professor of the KU Leuven Special Research Fund.
The authors thank Prof Andreas Von Leupoldt and Prof Diana
Torta for comments on an early version of the manuscript.
Article history:
Received 27 February 2020
Received in revised form 19 August 2020
Accepted 1 October 2020
Available online 5 October 2020
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