Functional Brain MRI to Understand Pain Phenotypes in Knee Osteoarthritis

This study will include patients with painful knee osteoarthritis (pain scoring ≥ 4/10 on the Numerical Rating Scale (NRS)). Patients matched by age (within 3 years) will be divided into two groups based on their PainDETECT score: those with nociceptive pain (score ≤ 12) and those with neuropathic pain (score > 13).

Participants will be recruited from three rheumatology centers (30 in Clermont-Ferrand, 15 at Saint-Antoine Hospital, and 15 at Pitié-Salpêtrière Hospital in Paris). The rheumatologist will verify eligibility and provide information during the pre-enrollment consultation, within 30 days prior to enrollment. After obtaining their informed consent, patients will attend the enrollment visit and be assigned to a group based on their PainDETECT score.

Each participant will undergo a clinical evaluation, including the following PRO measures: Lequesne and WOMAC functional indices, EuroQol EQ-5D, Hospital Anxiety and Depression Scale, fatigue and pain intensity scales, Catastrophizing Scale (PCS), ICOAP, OASIS, and Flare-OA scales. A QST test will also be performed using the Neogi method, which includes pressure pain thresholds, conditioned pain modulation, and temporal pain summation.

A blood test will be performed, including high-sensitivity CRP and metabolic markers (lipid profile, HbA1c, and fasting blood glucose), due to the link between metabolic syndrome and osteoarthritic pain.

Within 30 days of enrollment, participants will undergo an fMRI scan at the radiology department in Clermont-Ferrand or at La Pitié-Salpêtrière. On the day of the scan, participants will complete additional self-reports of knee pain using the questionnaires. Interpretation of the fMRI data will be centralized in Clermont-Ferrand.

Inclusion criteria

• Women aged 40 or older (only women will be included to ensure consistency in the analyses, given the higher prevalence of osteoarthritis in women and the influence of sex/gender on the experience of pain)
• Diagnosis of femorotibial osteoarthritis of the knee according to the 1986 American College of Rheumatology criteria
• Presence of knee pain with an intensity of ≥ 4/10 on a numerical rating scale (NRS)
• Chronic knee pain, i.e., lasting at least 6 months with at least 15 days of pain in the past 30 days
• Completion of the PainDETECT questionnaire, which will allow the patient to be assigned to one of two groups prior to the enrollment visit (those with nociceptive pain [score ≤ 12] and those with neuropathic pain [score > 13])
• Patients have read and understood the information letter
• Patients have signed the informed consent form
• Patients are enrolled in a social security program

Exclusion criteria

• Other joint diseases affecting the knees (gout, chondrocalcinosis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis)
• Conditions that, in the investigator's opinion, interfere with the assessment of osteoarthritic pain, such as conditions causing neuropathic pain in the lower extremities (e.g., peripheral neuropathy, chronic radiculopathy) or fibromyalgia
• Kellgren-Lawrence radiographic stage IV in one or both knees
• Patients with one or more knee prostheses
• Claustrophobia making MRI impossible
• Contraindication to MRI
• Pregnant or breastfeeding women
• Patients under guardianship, conservatorship, deprived of liberty, or under judicial protection
• Patients who have participated in an interventional clinical trial within the last 6 months that could impact the primary endpoint