Studying the Neurobiological Mechanisms of Non-specific Chronic Low Back Pain and Chronic Insomnia: a Four-group Cross-sectional Study
- Conditions
- Chronic Low Back Pain (CLBP)Chronic InsomniaNeuroinflammation
- Registration Number
- NCT06973837
- Lead Sponsor
- Vrije Universiteit Brussel
- Brief Summary
This study is a part of a larger project aiming to evaluate the neurobiological mechanisms underlying the bidirectional sleep-pain relationship in people with non-specific chronic low back pain. Specifically, this study aims to evaluate the neurobiological mechanisms underlying the relationship between chronic sleep disturbances and pain sensitivity in people with non-specific chronic low back pain and chronic insomnia.
- Detailed Description
Sleep disturbances, and especially insomnia, reflect one of the most common comorbidities in people with chronic pain, including people with chronic low back pain. Previous research has furthermore demonstrated that a lack of sleep is associated with an increased pain sensitivity. The goal of this study is to evaluate the role of brain neuroinflammation in the relationship between chronic sleep disturbances and both clinical and experimental pain sensitivity in people non-specific chronic low back pain and/or chronic insomnia.
Specifically, a cross-sectional study will be conducted across four age- and sex-matched study groups: healthy controls with good sleep habits (Group 1); people with non-specific chronic low back pain and good sleep habits (Group 2); pain-free individuals with chronic insomnia (Group 3); and people with non-specific chronic low back pain and comorbid chronic insomnia (Group 4). The study will be performed over nine consecutive days. On the first study day, all participants will be provided an online-based baseline questionnaire battery to be completed at home. During the following seven days, all participants will then complete a sleep diary once per day, provide momentary ratings of pain, sleepiness, fatigue, and affect eight times per day, and wear an Actigraph at all times (except during heavy water contact). During this seven-day period, the participants will also be instructed to collect a stool sample at a time of their own convenience, but preferably within the first three days, to be used for gut microbiota composition analyses. Continuous dietary intake will therefore also be recorded during the first three days of the seven-day period, while participants who are not able to collect their stool sample during any of these three days will continue to record their dietary intake until a stool sample has been collected. On the last study day (day nine), experimental pain sensitivity and pain-evoked brain activity will be assessed via quantitative sensory testing and a pain-task-based functional magnetic resonance imaging (fMRI), respectively, whereas markers of brain neuroinflammation will be measured via magnetic resonance spectroscopy and (multicompartment) diffusion-weighted magnetic resonance imaging. During the last study day, a venous blood sample will also be collected to measure systemic levels of short chain fatty acids. All participants will therefore also be provided standardized low-fiber meals, alongside standardized boluses of pure fiber, to consume in the evening before, and in the morning of their last study day.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Brain metabolite concentrations Main test day (Day 9) Concentration of brain metabolites measured using single-voxel magnetic resonance spectroscopy in five regions of interest: (1) pregenual anterior cingulate cortex (midline); (2/3) right/left thalamus; (4/5) right/left anterior insula.
- Secondary Outcome Measures
Name Time Method Daily self-reported affect (fluctuations) assessed via experience sampling methodology (m-Path smartphone application) Seven days before the main test day (Day 2-8) Positive and negative affect "right now" rated on a 0-to-100 visual analogue scale at eight block-randomized time points per day.
Daily self-reported fatigue (fluctuations) assessed via experience sampling methodology (m-Path smartphone application) Seven days before the main test day (Day 2-8) Mental and physical fatigue "right now" rated on a 0-to-100 visual analogue scale at eight block-randomized time points per day.
Daily self-reported sleepiness (fluctuations) assessed via the Karolinska Sleepiness Scale (KSS) implemented into the experience sampling methodology smartphone application (m-Path) Seven days before the main test day (Day 2-8) The KSS is a single-item questionnaire (i.e., scale) that measures subjective sleepiness at a specific moment in time. Scores range from 1 to 9, with higher scores indicating greater sleepiness. The scale was completed at eight block-randomized time points per day.
Daily sleep-wake cycles assessed by Actigraphy Seven days before and on the main test day (Day 2-9) Wrist-worn actigraphy (GT3X Actigraph, Pensacola, FL, USA) at all times except heavy water contact.
Daily self-reported perceived sleep duration assessed via sleep diaries Seven days before and on the main test day (Day 2-9) Subjective time points for when getting into and out of bed, and for sleep onset and offset, provided once per day.
Daily self-reported nighttime pain assessed via sleep diaries Seven days before and on the main test day (Day 2-9) Pain intensity during the preceding night, rated on a 0-to-10 numerical rating scale once per day.
Daily self-reported subjective sleep quality assessed via sleep diaries Seven days before and on the main test day (Day 2-9) Subjective sleep quality from the preceding night, rated on a 0-to-10 numerical rating scale once per day.
Daily self-reported subjective wake quality assessed via sleep diaries Seven days before the main test day (Day 2-8) Subjective wake quality during the day, rated on a 0-to-10 numerical rating scale once per day.
Serum short chain fatty acid levels Main test day (Day 9) Levels of short chain fatty acids analysed from serum aliquots derived from venous blood samples.
Microbiota composition One of the seven days preceding the main test day (Day 2-8) Composition-related outcomes (e.g., diversity, abundance) analysed from stool-sample aliquots.
Habitual self-reported macronutrient intake (including fibre) assessed via continuous dietary records (MyFitnessPal smartphone application) At least the first three, up to all of the seven days preceding the main test day (Day 2-8, dependent on the day at which a stool sample is collected) Macronutrient and fibre intake (in grams) estimated (via MyFitnessPal application) from continuous self-reported dietary intake (food diary).
Brain-tissue microstructure diffusivity Main test day (Day 9) Diffusivity data (diffusion-weighted signal) from different microstructural compartments within the brain (intra-axonal space, extra-axonal space, and free water) measured using diffusion-weighted magnetic resonance imaging.
Functional brain responses to evoked low back pain Main test day (Day 9) Blood-oxygen-level-dependent (BOLD) signal acquired during an evoked low back pain task performed during functional magnetic resonance imaging sequence.
Manual pressure pain detection thresholds (mPDT) Main test day (Day 9) Gradually increasing pressure (1 kgf/sec) applied using a manual pressure algometer (FPX50, Wagner Instruments, USA) until the first sensation of discomfort (mPDT) is (self-)reported. The measurement is repeated three times across six body sites: (1/2) right/left m. erector spinae; (3/4) right/left m. extensor carpi radialis; (5/6) right/left m. gastrocnemius.
Computerized pressure pain detection thresholds (cPDT) Main test day (Day 9) Gradually increasing pressure (1 kPa/sec) applied via a computer-controlled blood pressure cuff (Nocitech, Aalborg University, Denmark) around the calf (dominant leg) until a first sensation of discomfort (cPDT) is rated.
Computerized pressure pain tolerance thresholds (cPTT) Main test day (Day 9) Gradually increasing pressure (1 kPa/sec) applied via a computer-controlled blood pressure cuff (Nocitech, Aalborg University, Denmark) around the calf (dominant leg) until it is no longer tolerable.
Temporal summation of (pressure) pain Main test day (Day 9) Twelve repeated pressure stimuli (stimulus duration: 1 sec; interstimulus interval: 1 sec) applied via a computer-controlled blood pressure cuff (Nocitech, Aalborg University, Denmark) around the calf (dominant leg) at an intensity corresponding to the cPTT.
Conditioned (pressure) pain modulation Main test day (Day 9) One cPTT assessment via computer-controlled blood pressure cuff algometry (Nocitech, Aalborg University, Denmark) performed immediately before and after a 1-min hot water immersion of the hand contralateral to the stimulated calf (dominant leg).
Daily self-reported pain distribution assessed via experience sampling methodology (m-Path smartphone application) Seven days before the main test day (Day 2-8) A list of body regions from which participants select the regions at which they experience pain "right now", assessed at eight block-randomized time points per day.
Daily self-reported low back pain (fluctuations) assessed via experience sampling methodology (m-Path smartphone application) Seven days before the main test day (Day 2-8) Intensity, unpleasantness, and attention to low back pain "right now" rated on a 0-to-100 visual analogue scale at eight block-randomized time points per day.
Trial Locations
- Locations (1)
UZ/KU Leuven
🇧🇪Leuven, Belgium