Chronic Low Back Pain (CLBP)
Conditions
Keywords
chronic pain, back pain, physical exercise, inflammation, brain connectivity
Brief summary
This study is registered retrospectively for transparency. This mechanistic randomized controlled trial examined whether a 14-week supervised physical exercise training program reduces chronic low back pain (CLBP) by modulating frontostriatal brain connectivity and immune-related gene expression. Fifty-seven adults with CLBP were randomized to exercise training or wait-list control. Participants underwent pre- and post-intervention MRI, questionnaires, and blood sampling. The study tested whether reductions in nucleus accumbens-medial prefrontal cortex connectivity and changes in inflammatory gene expression mediated exercise-induced pain relief.
Detailed description
Chronic low back pain (CLBP) is associated with altered functional connectivity between the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), as well as systemic low-grade inflammation. This mechanistic randomized controlled trial evaluated the effects of a 14-week supervised physical exercise (PE) training program on pain intensity, functional disability, brain connectivity, and peripheral gene expression in individuals with CLBP. Participants were randomized to either: * Supervised exercise training (3 sessions per week, 60 minutes per session, 14 weeks), or * Wait-list control. Exercise sessions combined aerobic and resistance training. Exercise intensity was individually calibrated based on VO2max and 1 repetition maximum (1RM) assessments. Assessments conducted pre- and post-intervention included: * Resting-state functional MRI * Diffusion-weighted imaging * Self-reported pain and disability questionnaires * Cardiorespiratory and functional testing * Blood sampling for BDNF and RNA sequencing The primary mechanistic hypothesis tested whether changes in NAc-mPFC connectivity and immune-related gene expression mediated exercise-induced reductions in chronic pain. Therefore, primary outcomes focused on indices of target engagement (including immune gene expression and brain connectivity) rather than clinical efficacy alone. Note: This study was not registered prior to participant enrolment. The project was investigator-initiated and conceived as a mechanistic investigation prior to widespread mandatory registration requirements. Study recruitment and progress were also substantially influenced by the COVID-19 pandemic and associated lockdowns. The clinical efficacy of PE for CLBP is already well established. Consequently, the primary aim of the present study was to examine the biological mechanisms through which PE may influence pain. Registration is therefore being completed retrospectively to ensure transparency.
Interventions
BEHAVIORALSupervised physical exercise training
60-minute sessions 3 times weekly Aerobic + resistance training Individually calibrated intensity (VO2max, 1RM) Total duration: 14 weeks
Sponsors
McGill University
Canadian Institutes of Health Research (CIHR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Mechanistic trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Chronic low back pain ≥ 3 months * Pain present at least half the days over the past 6 months * Average pain intensity ≥ 3/10 during week prior to enrollment
Exclusion criteria
* Diabetes * Neurological disorder * Psychiatric disorder * Significant cardiorespiratory disease * Under 18 years of age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chronic Low Back Pain Intensity | Assessed at Baseline (Pre-intervention, Week 0) and Post-intervention (Week 14) | Self-reported average low back pain intensity measured using an 11-point Numerical Rating Scale (NRS; 0-10), where 0 = "no pain" and 10 = "worst imaginable pain." |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oswestry Low Back Pain Disability Index (ODI) | Assessed at Baseline (Week 0) and Post-intervention (Week 14) | Pain-related disability measured using the Oswestry Low Back Pain Disability Questionnaire (10 items). Each item is scored from 0-5, yielding a total score ranging from 0-50, with higher scores indicating greater disability. |
| Nucleus Accumbens-Medial Prefrontal Cortex Functional Connectivity | MRI acquired at Baseline (Week 0) and Post-intervention (Week 14) | Functional connectivity assessed using resting-state functional magnetic resonance imaging (rsfMRI). Seed-to-voxel analyses were performed using anatomically defined bilateral nucleus accumbens and medial prefrontal cortex regions. |
| Whole-Brain Intrinsic Connectivity | MRI acquired at Baseline (Week 0) and Post-intervention (Week 14) | Intrinsic connectivity analysis (voxel-wise network centrality; root mean square of all connections) performed using resting-state fMRI. |
| Fractional Anisotropy of NAc-mPFC White Matter Tract | MRI acquired at Baseline (Week 0) and Post-intervention (Week 14) | Fractional Anisotropy (FA) measured using diffusion-weighted imaging (DWI) probabilistic tractography along the white matter tract connecting the nucleus accumbens and medial prefrontal cortex. |
| Peripheral Blood Gene Expression (RNA Sequencing) | Blood samples collected prior to Session 7 (first calibrated-intensity session, Week 3) and prior to Session 42 (final session, Week 14) | Gene expression levels assessed in peripheral blood immune cells using RNA sequencing (DESeq2 analysis). Transcriptomic analyses evaluated differential gene expression and pathway enrichment. |
| Plasma Brain-Derived Neurotrophic Factor (BDNF) | Collected immediately before and after Session 7 (Week 3) and immediately before and after Session 42 (Week 14) | Plasma BDNF concentrations measured using Luminex multiplex assay (Human ProcartaPlex). The purpose of this outcome is to evaluate both acute and longer-term neurotrophic responses to exercise training. Acute changes were measured before and after high-intensity training sessions; long-term changes were assessed by comparing baseline levels across sessions. |
Countries
Canada
Outcome results
None listed