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.
Study Type
OBSERVATIONAL
Enrollment
140
Ghent University, Department of Rehabilitation Sciences
Ghent, Belgium
Quantitative sensory testing - pressure pain threshold
Determination of mechanical pain sensitivity with a digital pressure algometer, recorded in kg.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At baseline
Skin conductance
Skin conductance reflects sweat gland activity and will be measured continuously; providing information on the autonomic nervous system.
Time frame: 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.
Time frame: At baseline
Respiration rate
Respiration rate, the number of breaths taken per minute will be measured continuously; providing information on the autonomic nervous system.
Time frame: 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.
Time frame: At baseline
Visual Analogue Scale - Self-reported
Assessment of momentary pain, unpleasantness and stress on a VAS scale ranging from 0-100
Time frame: At baseline and at the 6-month follow-up
Pain Disability Index - Self-reported
Assessment of pain-related interference in daily activities, recorded on a 0-70 scale
Time frame: At baseline and at the 6-month follow-up
Pain Catastrophizing Scale - Self-reported
Measurement of catastrophic thinking related to pain, recorded on a scale of 0-52.
Time frame: At baseline and at the 6-month follow-up
Pain Vigilance and Awareness Questionnaire - Self-reported
Assessment of attention and awareness to pain, recorded on a 0-80 scale.
Time frame: At baseline and at the 6-month follow-up
General Perceived Recovery - Self-reported
11-point scale to rate perceived recovery from - 5 (vastly worse), through 0 (no change) to + 5 (greatly improved), to assess recovery or persistence of low back pain
Time frame: At baseline and at the 6-month follow-up
Pain Anxiety Symptoms Scale - Self-reported
Assessment of fear and anxiety associated with pain, recorded on a 0-100 scale.
Time frame: At baseline and at the 6-month follow-up
Positive and Negative Affect Schedule - Self-reported
Measurement of positive and negative affect levels. Total scores for positive and negative affect range for 10-50 separately.
Time frame: At baseline and at the 6-month follow-up
Brief Resilience Scale - Self-reported
Measurement of the ability to recover from stress, recorded on a 5-point Likert scale. This questionnaire contains 6 items.
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Time frame: At baseline and at the 6-month follow-up
Intolerance of Uncertainty Scale - Self-reported
Assessment of intolerance to uncertainty, recorded on a scale of 1-5 for each item, with 12 items in total.
Time frame: At baseline and at the 6-month follow-up
Stress Mindset Measure - Self-reported
Evaluation of beliefs about the nature of stress (enhancing vs. debilitating), recorded on a scale of 0-4 for each item, with 8 items in total.
Time frame: At baseline and at the 6-month follow-up
Perceived Stress Scale - Self-reported
Measurement of perceived stress over the past month, recorded on a scale of 0-40.
Time frame: At baseline and at the 6-month follow-up
Hospital Anxiety and Depression Scale - Self-reported
Assessment of anxiety and depression symptoms, recorded on a scale of 0-21 for anxiety and depression subscales separately.
Time frame: At baseline and at the 6-month follow-up
Childhood Trauma Questionnaire - Self-reported
Measurement of childhood trauma experiences. A shortened version will be used with scores ranging from 0-25. Emotional abuse, physical abuse, and neglect components will be assessed.
Time frame: At baseline and at the 6-month follow-up
Pittsburgh Sleep Quality Index - Self-reported
Measurement of sleep quality over the past month. A shortened version will be used with scores ranging from 0-12. Component 1-4 will be scored.
Time frame: At baseline and at the 6-month follow-up
Gender and Pain Questionnaire - Self-reported
Collection of scales of measures for gender conceptualization, gender identity and gendered pain beliefs
Time frame: At baseline and at the 6-month follow-up
T1 weighted anatomical MRI data
Through Magnetization Prepared-Rapid Gradient Echo, macro-structural properties of grey matter, such as surface area, cortical thickness or volume will be characterized.
Time frame: At baseline and at the 6-month follow-up
Resting state functional MRI
This type of MRI-scan will allow us to evaluate functional connectivity of the brain.
Time frame: At baseline and at the 6-month follow-up
Diffusion weighted MRI data
Diffusion weighted MR imaging will provide insights in microstructural properties of white matter (i.e., factional anisotropy, mean diffusivity, etc.).
Time frame: At baseline and at the 6-month follow-up
Pseudo-Continuous Arterial Spin Labeling - MRI
This type of MRI will provide information on brain blood perfusion parameters.
Time frame: At baseline and at the 6-month follow-up
Quantitative sensory testing - pressure pain threshold (at follow-up)
Determination of mechanical pain sensitivity with a digital pressure algometer, recorded in kg.
Time frame: At the 6-month follow-up
Quantitative sensory testing - heat pain suprathreshold (at follow-up)
Determination of the mean of heat pain threshold and heat pain tolerance with TSA-2, recorded in °C.
Time frame: At the 6-month follow-up
Quantitative sensory testing - conditioned pain modulation (at follow-up)
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.
Time frame: At the 6-month follow-up
Quantitative sensory testing - temporal summation of pain (at follow-up)
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.
Time frame: At the 6-month follow-up
Task-based functional MRI - experimental pain induction task (at follow-up)
This type of functional MRI-scanning will allow to capture acute brain responses to (painful) heat stimuli and processes of pain modulation.
Time frame: At the 6-month follow-up
Salivary cortisol concentration (at follow-up)
Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse cortisol concentrations; providing information about the hypothalamus-pituitary-adrenal-axis functioning.
Time frame: At the 6-month follow-up
Salivary alpha-amylase concentration (at follow-up)
Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse alpha-amylase concentrations; providing information about the autonomic nervous system functioning.
Time frame: At the 6-month follow-up
Salivary oxytocin concentration (at follow-up)
Saliva samples will be taken, with a swab under the tongue for 2 minutes to analyse oxytocin concentrations; providing information on the oxytocinergic system.
Time frame: At the 6-month follow-up
Heart rate (at follow-up)
Heart rate, the number of times the heart beat within a certain period, will be measured with ECG continuously, and is part of the autonomic nervous system.
Time frame: At the 6-month follow-up
Heart rate variability (at follow-up)
Heart rate variability, the fluctuations in time between heart beats, will be measured with ECG continuously. Both time domains and frequency domains of HRV will be examined. This parameter is part of the autonomic nervous system.
Time frame: At the 6-month follow-up
Skin conductance (at follow-up)
Skin conductance reflects sweat gland activity and will be measured continuously; providing information on the autonomic nervous system.
Time frame: At the 6-month follow-up
Skin temperature (at follow-up)
Skin temperature, the measurement of the temperature at the skin's surface will be measured continuously; providing information on the autonomic nervous system.
Time frame: At the 6-month follow-up
Respiration rate (at follow-up)
Respiration rate, the number of breaths taken per minute will be measured continuously; providing information on the autonomic nervous system.
Time frame: At the 6-month follow-up
Blood pressure (at follow-up)
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.
Time frame: At the 6-month follow-up