Mapping Stress and Pain Interactions (G072323N)

NCT06892977 | Enrolling By Invitation

• 1 other identifier: ONZ-2024-0391
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The over-arching goal of this observational (case-control, with a cross-sectional and longitudinal arm) study is to comprehensively map stress system (dys)function (including reactivity and recovery) in people with primary musculoskeletal (MSK) pain and a pain-free control group.

• The primary objective is to characterize stress systems functioning and their relation to pain in individuals with subacute versus chronic, and localized versus widespread MSK pain, and compare to pain-free controls.
• The secondary objective is to define the contribution of stress system functioning to trajectories of MSK pain, including pain chronification or recovery from pain. Researchers will compare primary musculoskeletal pain groups with pain-free controls. Participants will:
• Fill out online questionnaires.
• Provide a sample of hair and saliva to assess chronic and acute stress hormone levels, respectively. Saliva samples will be collected both in the lab and at home.
• Be subject to psychophysiological monitoring.
• Partake in quantitative sensory testing measuring pain thresholds, tolerances and pain modulation of pressure and heat. These tests will be repeated twice: before and after an acute-stress induction task.
• Partake in a series of stress-inducting tasks.
• Be subject to MRI-scans of the brain, including structural and functional MR acquisitions (e.g., during rest and during pain inductions). Participants will be invited for a second session of the same assessments six months later to observe possible connection between pain trajectory and stress system (dys)function.

Conditions

Fibromyalgia; Chronic Low Back Pain; Subacute Low Back Pain

Keywords

Stress system; Musculoskeletal pain; Pain chronification; Pain processing; Neural correlates of pain; Stress reactivity; Stress recovery; Autonomic nervous system (ANS); Hypothalamus-pituitary-adrenal axis (HPA axis); Chronic widespread pain; Chronic localized pain; Oxytocin; Low back pain; Fibromyalgia

Outcome Measures

Primary Outcomes (14)

• Quantitative sensory testing - pressure pain threshold

  Determination of mechanical pain sensitivity with a digital pressure algometer, recorded in kg.

  At baseline

• Quantitative sensory testing - heat pain suprathreshold

  Determination of the mean of heat pain threshold and heat pain tolerance with TSA-2, recorded in °C.

  At baseline

• Quantitative sensory testing - conditioned pain modulation

  Determination of conditioned pain modulation with a parallel protocol, with test stimulus and conditioning stimulus equal to the heat pain suprathreshold temperature. Pain will be scored on a verbal rating scale 0-100.

  At baseline

• Quantitative sensory testing - temporal summation of pain

  Determination of temporal summation of pain with a tonic protocol. Heat stimuli will be applied for two minutes, with the temperature equal to the heat pain suprathreshold. Pain will be scored on a verbal rating scale 0-100.

  At baseline

• Task-based functional MRI - experimental pain induction task

  This type of functional MRI-scanning will allow to capture acute brain responses to (painful) heat stimuli and processes of pain modulation.

  At baseline

• Salivary cortisol concentration

  Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse cortisol concentration; providing information about the hypothalamus-pituitary-adrenal-axis functioning.

  At baseline

• Salivary alpha-amylase concentration

  Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse alpha-amylase concentrations; which gives information about the autonomic nervous system functioning.

  At baseline

• Salivary oxytocin concentration

  Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse oxytocin concentrations; providing information about the oxytocinergic system.

  At baseline

• Heart rate

  Heart rate, the number of times the heart beat within a certain period, will be measured continuously using ECG (electrocardiogram), providing information on the autonomic nervous system.

  At baseline

• Heart rate variability

  Heart rate variability (HRV), the fluctuations in time between heart beats, will be measured continuously using ECG. Both time domain and frequency domain of HRV will be examined; providing information on the autonomic nervous system.

  At baseline

• Skin conductance

  Skin conductance reflects sweat gland activity and will be measured continuously; providing information on the autonomic nervous system.

  At baseline

• Skin temperature

  Skin temperature, the measurement of the temperature at the skin's surface will be measured continuously; providing information on the autonomic nervous system.

  At baseline

• Respiration rate

  Respiration rate, the number of breaths taken per minute will be measured continuously; providing information on the autonomic nervous system.

  At baseline

• Blood pressure

  Blood pressure, the force exerted by circulating blood on the walls of blood vessels, will be measured using non-continuously; providing information on the autonomic nervous system.

  At baseline

Secondary Outcomes (33)

• Visual Analogue Scale - Self-reported

  At baseline and at the 6-month follow-up

• Pain Disability Index - Self-reported

  At baseline and at the 6-month follow-up

• Pain Catastrophizing Scale - Self-reported

  At baseline and at the 6-month follow-up

• Pain Vigilance and Awareness Questionnaire - Self-reported

  At baseline and at the 6-month follow-up

• General Perceived Recovery - Self-reported

  At baseline and at the 6-month follow-up

Study Arms (4)

fibromyalgia

Proof of a primary fibromyalgia diagnosis with chronic widespread pain by a specialist-doctor, with an average pain intensity of ≥2/10 on a Visual Analogue Scale, and with pain-related disability indicated by a score of ≥14/70 on the Pain Disability Index.

chronic low back pain

Chronic primary (non-specific) low back pain with primary onset ≥6 months ago, with an average pain intensity of ≥2/10 on a Visual Analogue Scale, and with pain-related disability indicated by a score of ≥14/70 on the Pain Disability Index.

subacute low back pain

Non-specific low back pain with primary onset \<3 months ago, with an average pain intensity of ≥2/10 on a Visual Analogue Scale, and with pain-related disability indicated by a score of ≥14/70 on the Pain Disability Index.

pain-free/healthy control

Exclusion criteria include current pain (\>0 on a Visual Analogue Scale); a pain condition in the last 6 months for which treatment was sought; history of a chronic pain syndrome.

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Study population is a community sample.

You may not qualify if:

• Body weight \>150 kg (maximum weight for the MRI scanner).
• Postmenopausal individuals.
• Use of hormone replacement therapy.
• Current or history of severe psychiatric, neurological (related to the brain, spinal cord, or nerves), endocrine (related to the hormonal system), or cardiovascular (related to the heart and blood vessels) conditions (e.g., cancer, cardiovascular disease, epilepsy, diabetes, etc.).
• History of spinal surgery, spinal trauma, severe spinal deformities, or neurogenic back pain.
• Having a severe communicative or cognitive disorder.
• Use of medication that is not stable for at least 1 month prior to the test session.
• Regular drug use (≥1 time per week).
• Contraindications for MRI (such as claustrophobia, implanted electronic devices like a pacemaker, metal splinters in the body, etc.).
• Currently pregnant or have been pregnant in the past year.
• Breastfeeding.

Sponsors & Collaborators

• University Ghent: lead
• Vrije Universiteit Brussel: collaborator
• Tilburg University: collaborator

Study Sites (1)

Ghent University, Department of Rehabilitation Sciences

Ghent, 9000, Belgium

Location

Related Publications (1)

• Moerkerke M, Vyverman J, De Baere R, Clement P, Smeets T, Coppieters I, Timmers I, Van Oosterwijck J. A comprehensive mapping of stress system interactions with pain and their contribution to chronification of musculoskeletal pain: Protocol of the STRAIN study. PLoS One. 2025 Jun 24;20(6):e0324089. doi: 10.1371/journal.pone.0324089. eCollection 2025.

  PMID: 40554512 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Saliva to examine current alpha-amylase, cortisol and oxytocin levels. Hair to examine cortisol levels over the last 3 months.

MeSH Terms

Conditions

Fibromyalgia; Musculoskeletal Pain; Chronic Pain; Low Back Pain

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Back Pain

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: March 25, 2025
• Study Start: February 8, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

BE (1)