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


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).

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: November 30, 2021


  • Device: Magnetic Resonance Imaging
    • Magnetic Resonance Imaging. Pain testing: Temporal summation, Pain thresholds. Assessment of symptoms: Questionnaires. All interventions are made at baseline only (1 time/subject).

Arms, Groups and Cohorts

  • Patients with disc degenerative disease (DDD)
    • 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.
  • Healthy controls (HC)
    • Healthy controls matched according to age and sex, no chronic pain conditions.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 30 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Karolinska Institutet
  • Provider of Information About this Clinical Study
    • Principal Investigator: Eva Kosek, Principal Investigator, Professor, MD – Karolinska Institutet
  • Overall Official(s)
    • Eva Kosek, Prof, MD, Principal Investigator, Karolinska Institutet
  • Overall Contact(s)
    • Eva Kosek, Prof, MD, 4685248000000,

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