Chronic Widespread Pain
Conditions
Keywords
Chronic Widespread Pain, Epigenetics, Autonomic Nervous System, Stress Intolerance
Brief summary
Patients with chronic widespread pain (CWP) frequently experience stress intolerance - an exacerbation of symptoms in response to stress. Although it severely affects their quality of life, stress intolerance remains a mystery. Hence, unravelling the mechanisms underlying stress intolerance is crucial to understand CWP pathophysiology and to develop novel treatments. Epigenetic mechanisms hold the potential to provide an answer as they have been found to be altered in patients with CWP at baseline, and in response to stress. However, research on epigenetic mechanisms in CWP is very scarce. Hence, this study aims to address this knowledge gap by assessing stress-induced epigenetic changes in patients with CWP and healthy controls aiming to unravel whether epigenetic mechanisms can help explain stress intolerance. The regulatory role of epigenetic mechanisms will be researched in relation to the activity of enzymes affected by the epigenetic mechanisms, neurophysiological measures, and stress-induced symptom changes in patients with CWP.
Detailed description
The objectives of this project will be tackled by a randomized cross-over study including 44 patients with CWP and 44 healthy controls. Participants are expected to come to the hospital twice and fill in questionnaires at several defined timepoints. Two days before their first visit, participants will complete baseline questionnaires at home via REDCap, which will take approximately one hour. Next, participants will be randomised into Group 1 (undergoing the mental stress test at their first visit and then relaxation breathing) or Group 2 (undergoing relaxation breathing at their first visit and then the mental stress test). During each hospital visit, the participants will be assessed before, during and after the intervention. The Pre-test assessment consists of a blood withdrawal, five short questionnaires, examination of pain thresholds, and neurophysiological measurements. The latter will continue during the intervention, which consists of a mental stress test or relaxation breathing. The Post-test assessment consists of a blood withdrawal, one short questionnaire, examination of pain thresholds, and neurophysiological measurements. Then there are again 2 home-based assessments via REDCap 24h and 7 days after the intervention during which the participants will in 1 or 5 short questionnaires, respectively.
Interventions
A mental stress test that induces stress via a series of arithmetic tasks participants need to solve in a few seconds.
OTHERRelaxation breathing
3 short sessions (4 minutes) of relaxation breathing
Sponsors
Research Foundation Flanders
KU Leuven
Vrije Universiteit Brussel
Study design
Observational model
CASE_CROSSOVER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* female * age between 18 and 70 years old * body mass index (BMI) below 30 * inactive lifestyle * for patients only: received the diagnosis of fibromyalgia
Exclusion criteria
* other neurological, endocrine, cardiac, or systemic syndromes * history of cancer or heart failure * women that are pregnant or within one year after pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA methylation of catecholamine-degrading enzymes | At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing | DNA methylation status of catechol-O-methyltransferase (COMT), monoamine oxidase (MAO)-A and MAO-B |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic variations in catecholamine-degrading enzymes | At baseline | COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680; MAO-A: rs6323; MAOA-uVNTR; MAO-B: rs1799836 |
| Catecholamine levels | At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing | Levels of adrenaline, noradrenaline and dopamine in plasma |
| Heart rate variability | Continuously starting 10 minutes before until 10 minutes after the mental stress test and relaxation breathing | Heart rate variability measured continuously using the Polar H10 |
| Activity of catecholamine-degrading enzymes | At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing | Activity of the enzymes will be defined in plasma or PBMCs |
| Symptom severity | At baseline (i.e. before the mental stress test or relaxation breathing), and 10 minutes, 24 hours and 7 days after the mental stress test and relaxation breathing | Symptom severity which is assessed through the Chronic Fatigue Syndrome Symptom List |
| Blood pressure | At baseline (i.e. before the mental stress test or relaxation breathing), during (3 times with 4 minutes in between) and 10 minutes after the mental stress test and relaxation breathing | Blood pressure, both systolic and diastolic, measured at specified moments using a digital device |
Other
| Measure | Time frame | Description |
|---|---|---|
| Temperature and pressure pain thresholds | At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing | Pain thresholds for warmth and cold measured with the TSA-II, and pressure measured with a digital algometer on the hand and leg. Pain intensity is reported through a numeric rating scale ranging from 0 (no pain) to 10 (worst pain). |
| Level of stress | At baseline (i.e. before the mental stress test or relaxation breathing), during (3 times with 4 minutes in between) and 10 minutes, 24 hours and 7 days after the mental stress test and relaxation breathing | Numeric rating scale ranging from 0 (no stress) to 10 (worst stress) indicating the level of stress |
Countries
Belgium
Outcome results
None listed