Mapping Stress and Pain Interactions (G072323N)

Official title

STRAIN (STRessinpAIN): a Comprehensive Mapping of Stress System Interactions with Pain and Their Contribution to Extent and Chronification of Musculoskeletal Pain

Overview

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.

Primary outcome measures

• Quantitative sensory testing - pressure pain threshold [Time frame: At baseline]
• Quantitative sensory testing - heat pain suprathreshold [Time frame: At baseline]
• Quantitative sensory testing - conditioned pain modulation [Time frame: At baseline]
• Quantitative sensory testing - temporal summation of pain [Time frame: At baseline]
• Task-based functional MRI - experimental pain induction task [Time frame: At baseline]
• Salivary cortisol concentration [Time frame: At baseline]
• Salivary alpha-amylase concentration [Time frame: At baseline]
• Salivary oxytocin concentration [Time frame: At baseline]
• Heart rate [Time frame: At baseline]
• Heart rate variability [Time frame: At baseline]

Secondary outcome measures (12)

• Visual Analogue Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Pain Disability Index - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Pain Catastrophizing Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Pain Vigilance and Awareness Questionnaire - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• General Perceived Recovery - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Pain Anxiety Symptoms Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Positive and Negative Affect Schedule - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Brief Resilience Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Intolerance of Uncertainty Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Stress Mindset Measure - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Perceived Stress Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]
• Hospital Anxiety and Depression Scale - Self-reported [Time frame: At baseline and at the 6-month follow-up]

Eligibility criteria

Inclusion criteria

• Participants aged 18 to 45 years with a BMI between 18.5 and 35 kg/m², who are proficient in the Dutch language and do not meet the exclusion criteria listed below

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Other

Study locations

Belgium · 1 center

• Ghent University, Department of Rehabilitation Sciences — Ghent

Publications

• 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

Identifiers

NCT: NCT06892977 · ONZ-2024-0391

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗