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

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 Overview

• Status: Terminated
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Device: Magnetic Resonance Imaging

• Study Type: Observational
• Enrollment (Actual): 41

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 171 77
    • Karolinska Institute
  • Stockholm, Sweden
    • Karolinska Insitutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited through clinical collaborators (Stockholm Spine Center, Rygg Kirurgisk Centrum); HC will be recruited via online advertisement on the institution's website

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	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).
Healthy controls (HC); Healthy controls matched according to age and sex, no chronic pain conditions.	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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Eva Kosek, Prof, MD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: 2019-01142_1pre

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No