Brain Imaging of Pain-Related Processing and Structural Properties in Disc Degenerative Disease

Study Overview
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Brief Summary
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In this study, we apply brain MR imaging techniques at 3 Tesla to assess pain-relevant processing in patients with disc degenerative disease (DDD) scheduled for back surgery and age- and gender-matched controls without back pain. Data collection pre-surgery is performed over two days: On the first day, all participants undergo a battery of questionnaires relevant for individuals with chronic pain and pain sensitivity testing, including temporal summation and pressure pain thresholds. On the second day, participants undergo a MRI protocol, which includes functional MRI (fMRI) and diffusion tensor imaging to assess microstructural properties and structural connectivity. During fMRI, an experimental pressure pain paradigm is performed at the calf i.e. a location not connected to patients' chronic pain condition. Instead, the experimental pain paradigm serves as a condition to test processing of noxious stimulation unrelated to patients' experienced chronic pain. The noxious input pressure is individually calibrated to 50 on a 0-100 VAS scale to ensure that individual pain perceptions, despite different pressure intensities, are comparable across participants. The sensory stimulation will consist of a low standardized pressure intensity (150kPa). In an additional fMRI paradigm, participants do not receive stimulation but are instructed to continuously rate fluctuating spontaneous ongoing back pain (DDD) or perceived unpleasantness (controls). This project aims at investigating measures of brain architecture, neural response connected with evoked pain, connectivity (structural and functional) and pain-relevant psychometrics and questionnaire data in disc degenerative disease patients scheduled for back surgery. Specifically, MRI is performed to test whether i) patients display differences in properties of the mesolimbic circuit compared to healthy individuals and ii) behavioural as well as clinical characteristics related to the acquired MRI markers. This study is intended to serve as a baseline in a longitudinal project testing associations with between findings at baseline and following surgery (fusion/disc implants).

Official Title
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Brain Imaging of Pain-Related Processing and Structural Properties in Disc Degenerative Disease

Conditions
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Degenerative Disc Disease

Intervention / Treatment
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* Device: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Inclusion criteria: 30-60 year Right-handed DDD patients: Radiologically verified DDD and DDD pain as their main pain complaint Exclusion Criteria: previous spine surgery significant pain problems due to other causes and/or other chronic pain syndromes inflammatory rheumatic diseases neurological/psychiatric disorders severe cardiovascular disease substance abuse BMI>40 Contraindication to MRI

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with disc degenerative disease (DDD)<br>Patients suffering from disc degenerative disease, age 30-60 years that are on the waiting list for surgery (fusion/disc implants) at Stockholm Spine Center, Stockholm, Sweden. | Device: Magnetic Resonance Imaging<br>* Magnetic Resonance Imaging. Pain testing: Temporal summation, Pain thresholds. Assessment of symptoms: Questionnaires. All interventions are made at baseline only (1 time/subject).<br>|
| Healthy controls (HC)<br>Healthy controls matched according to age and sex, no chronic pain conditions. | Device: Magnetic Resonance Imaging<br>* Magnetic Resonance Imaging. Pain testing: Temporal summation, Pain thresholds. Assessment of symptoms: Questionnaires. All interventions are made at baseline only (1 time/subject).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional magnetic resonance imaging (rsfMRI) | Analysis of network connectivity during resting state | Baseline | 
| Functional magnetic resonance imaging (BOLD) | cerebral pain related activation following evoked pressure pain stimuli | Baseline | 
| Diffuse Tensor Imaging | White matter microstructure (e.g. structural connectivity) | Baseline | 
| Pressure pain thresholds | Pressure allometry (mmHg) | Baseline | 
| Temporal summation | Pain ratings during repeated pressure stimuli, ratings from 0-100, with 100 being worst pain imaginable | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity ratings | Visual analogue scale, 0-100 mm, 100 mm, worst possible pain | Baseline | 
| Oswestry Disability Index | 0-100, 0=no disability, 100= worst disability | Baseline | 
| Fibromyalgia criteria-2016 revision (American College of Rheumatology) | Calculation of FMness score, 0-31, 0 = no symptoms, 31 = worst symptoms | Baseline | 
| Multidimensional Fatigue Inventory | Total fatigue score, range 20-100, 100 = worst fatigue | Baseline | 
| Pain catastrophizing scale | Total score 0-52, high values more catastrophizing | Baseline | 
| Beck Depression Inventory | Scores 0-63, with 63 highest depression | Baseline | 
| State-Trait Anxiety Inventory | Scores 20-80 for state and 20-80 for trait anxiety, higher levels indicate more anxiety | Baseline | 
| EuroQual-5D | Scale ranging from -0.224 to 1, with 1 being highest possible health related quality of life | Baseline |