Functional brain imaging of the influence of interoceptive awareness and autonomic nervous system function in pain processing in fibromyalgia

Fibromyalgia is a common chronic pain disorder which mechanisms remain largely
unknown. Fibromyalgia predominantly affects women and is characterized by
symptoms of widespread musculoskeletal pain and discomfort on palpation of
specific sites known as tender points. Fibromyalgia results in long-term
sickness, inability to work, and repeated visits to medical practice. An
important feature of fibromyalgia is the heightened report of bodily sensations
compared to other disorders such as rheumatoid arthritis. Studies show that
fibromyalgia patients have elevated basal sympathetic nervous system activity
levels. Further, imaging studies show that brain regions implicated in pain
processing largely overlap those involved in autonomic control, e.g.,
prefrontal, anterior cingulate and insular regions. Importantly, fibromyalgia
patients show altered brain activity within these particular cortical areas.

This study will investigate the relationship between autonomic nervous system
function and pain in fibromyalgia, with a specific emphasis on awareness of
bodily sensations, also refered to as interoceptive awareness, as a potential
modulator of pain augmentation. The first objective of this study will be to
examine the resting state of the brain in relation to autonomic nervous system
function. Connectivity of the ventromedial prefrontal cortex will be examined
in fibromyalgia patients compared to healthy subjects. The second objective
will be to identify autonomic nervous system mechanisms underlying augmented
cortical processing of pain. Sympathetic activation levels will be measured and
correlated with brain activation patterns during rest and during painful
stimulation. In addition, the healthy volunteers will be split into two groups
based on their interoceptive awareness score as assessed by a heartbeat
perception task to determine if increased interoceptive awareness induces brain
activation changes. The third objective will be to assess the effect of
increased attentional focus to bodily sensations, also referred to as
hypervigilance. The fourth objective will be to assess whether physical fitness
levels are predictive of altered pain sensitivity levels in patients with
fibromyalgia.

This study requires one or two visits of 2.5-3 hours per visit. On the first
visit, subjects will be screened for study participation. Inclusion- and
exclusion criteria will be verified and informed consent will be signed. At
this visit, autonomic nervous system functioning will be assessed with measures
of heart beat, cardiac output, blood pressure, skin temperature, oxygenation of
blood, and skin conductance. Also, pain intensity scores will be determined on
a 0-100 visual analog scale using a conventional pressure algometer. In a
selected sample, the effects of attentional focus on internal or external
applied stimuli on pain threshold and pain tolerance measures will be tested by
using a cold pressor test (CPT). On the second visit, a select group of
subjects will undergo MRI scanning while autonomic nervous system measures are
continuously monitored. During MRI scanning, non-painful and painful pressure
stimuli will be applied to the thumbnail with the pressure stimulation device.
Also, attentional focus to interoceptive (heart beat) or exteroceptive signals
(weak electrical stimuli) will be manipulated. Another select group of patients
will be asked to participate in a more detailed examination on the relationship
between pain, as assessed by quantitative sensory testing (QST), and physical
fitness which will be assessed by two fitness tests (VO2max cycle test and a
6-minute walking test). Subjects will be asked to fill out some questionnaires.
Travel expenses will be reimbursed and in addition participants will be paid 7
euros for each hour participating in this study.

Risks associated with participation in this study are minimal. The equipment
used to test pain and acquire physiological data is commonly used in clinical
practices. Risks associated with scanning procedures are minimal. An
unforeseeable risk releated to participation in this study is the possible
discovery of claustrophobia when entering the small MRI scanning space which
may be unknown to the subject. Sport physicians will supervise the physical
fitness tests, and necessary cardiovascular screening will take place before
the maximal physical effort tests. Subjects will be able to terminate study
participation at any time in case this happens or for any other reason.