Effects of expectations on pain perception and learning in fibromyalgia patients

Chronic pain is one of the most burdensome health conditions worldwide,
affecting approximately 20% of the world population 1. Unlike acute pain,
chronic pain serves no biological purpose, has long-lasting disabling effects,
and is associated with an array of psychological, social and economic costs
2-5. Many cases of chronic pain remain medically unexplained as they lack a
clear peripheral pathology. Interestingly, recent neuroimaging studies have
revealed altered brain structure and function in chronic-pain patients 6-8.
This suggests that alterations at the brain level, and of related *top-down*
psychological/cognitive processes*including fear, avoidance, expectations,
memory and learning*may play an important role in the development and
maintenance of chronic pain 9-11. However, empirical studies examining
(aberrant) cognitive processes in chronic pain patients are rare; hence the
contribution of psychological influences to the pathology of chronic pain is
still largely unknown.

Studies in healthy participants, on the other hand, have provided ample
evidence that pain perception can be strongly modulated by psychological
processes, such as expectations and attention 12,13. In the proposed research,
we will focus on the effects of expectations. Multiple studies have shown that
expectations about pain*induced by previous experiences and/or instructions*
result in the adjustment of pain responses toward the expected pain level
14-16. Moreover, the effects of prior expectations on pain often persist, or
even grow over time, even when these expectations are not, or no longer, valid
16-19. That is, expectations about pain can become *self-fulfilling prophecies*
that are resistant to extinction. We recently demonstrated two, not mutually
exclusive, mechanisms promoting such self-reinforcing expectancy effects on
pain in healthy participants 20. First, we found that participants* pain
perception was biased toward their expected pain levels, creating a positive
feedback loop between expectations and pain perception. Second, participants
showed a *confirmation bias* in learning, such that expectation updating was
stronger (i.e., learning rate was higher) when new pain experiences confirmed,
than when they disconfirmed, prior expectations. Both of these effects varied
substantially across healthy individuals 20.

Self-reinforcing expectancy effects on pain perception may promote the
development and maintenance of a chronic pain syndrome. Indeed, the inability
to extinguish pain memories has been proposed as a defining aspect of chronic
pain 21,22. Furthermore, a few studies have demonstrated impaired cue-pain
contingency learning in chronic pain patients, with a particular impairment in
safety learning 9,11, which may reflect a confirmation bias. However, these
studies focused on the acquisition of pain expectations and did not examine the
(resistance to) extinction. Chronic pain has also been related to aberrant
perceptual processing 23, but the specific roles of perceptual and learning
processes in the development and maintenance of chronic pain remain to be
clarified 24. In the proposed research, we will address these issues, by
examining the effects of prior cue-based expectations on both pain perception
and extinction learning in chronic pain patients compared to healthy control
participants. We will focus on fibromyalgia, one of the most common types of
chronic pain conditions that is characterized by widespread musculoskeletal
pain, often without a clear medical explanation.

In addition to assessing expectancy effects of pain perception and pain-related
learning, we will also examine potential differences between fibromyalgia
patients and healthy participants in sensitivity to non-painful sensory
(visual) stimulation. In addition to greater pain sensitivity, reduced
tolerance to innocuous auditory, visual, olfactory, and tactile stimuli has
been reported in fibromyalgia patients 25-30. These observations have mostly
been obtained from self-report questionnaires about daily life sensations. In
agreement with the self-report data, significant brain-related abnormalities
have been observed in response to visual and auditory stimuli in fibromyalgia
patients 23,25,31,32. These multisensory processing abnormalities may reflect
an important pathophysiological mechanism underlying pain in fibromyalgia
patients. However, specific measures about the magnitude and reliability of
such alterations, obtained in a controlled experimental setting, are currently
lacking.

1. To assess whether the extinction of pain expectations differs between
fibromyalgia patients and healthy participants
* If so, to assess whether this is due to stronger expectancy-based modulation
of pain perception and/or a stronger confirmation bias in expectation updating
2. To assess whether fibromyalgia patients and healthy participants differ in
their sensitivity to visual stimulation and/or in the ability to discriminate
different intensities of visual stimulation

The proposed study will use a case-control design, comparing a group of 30
fibromyalgia patients to a group of 30 healthy control participants matched on
age, gender, and educational level. We will collect behavioral and
physiological (skin conductance) data from all participants, during a number of
experimental tasks (see section 5.2). All tasks will be administered in the
LUMC, and this will take approximately 2 hours in total (including a short
break). In addition, all participants will complete several questionnaires (see
section 5.2) at home via Qualtrics, prior to the test day, which will take
20-30 minutes.

There are no serious risks associated with participation in this study. We have
ample experience with thermal stimulation, it is without major side effects.
The used equipment is limited to avoid thermal burns to the skin. A red
discoloration of the skin can occur after testing, which usually resolves
within several hours.
Participants will receive monetary compensation for their time, but there is no
other direct benefit to the participants from this proposed research. However,
the potential knowledge gained from this study has greater benefits to society:
Although several types of chronic pain disorders are believed to arise, at
least partly, from dysfunctional neurocognitive processes, there has been a
paucity of empirical studies investigating this idea. The detection and
characterization of potential learning and perception biases in fibromyalgia
patients in the proposed study can help understand the mechanisms underlying
the development and maintenance of this chronic-pain disorder, which may
eventually contribute to the development of new treatment protocols.