Exercise Therapy in Combination With Central Nervous System-targeted Treatment for Osteoarthritis

The aim of this study is to investigate if exercise therapy comprising the NEMEX program in combination with a CNS-targeted treatment using GMI and SDT is superior to exercise therapy alone in improving self-reported pain, function, quality of life and objective measures related to hyperexcitability of the CNS (e.g. central sensitization) in people with KOA.

Participants will be randomized to one of two treatments initiated after randomization: the NEMEX program combined with a CNS-focused protocol or the NEMEX program alone.

The NEMEX program will consist of 12-weeks of individualized and supervised exercise sessions applied twice weekly (n=24 sessions). Each exercise session will last approximately 60minutes and include three parts: warming up, a circuit program and cooling down.

The CNS-targeted treatment will consist of 12-week individualized and supervised sessions applied twice weekly. Each training session will last approximately 30 minutes and include three parts, which are further explained below: 1) discussion of the participant's knee pain experience from a pain neuroscience perspective, 2) graded SDT and 3) GMI training.

Eligibility Criteria:
Inclusion Criteria:

* Patients with symptomatic and radiographically-confirmed tibiofemoral KOA (e.g. Kellgren-Lawrence ≥2, scored by an orthopaedic surgeon, not scheduled for total knee replacement \[decision among other factors based on pain, function and radiographic severity.
* Diagnosis of KOA according to the EULAR classification criteria: adults aged \>40 years with usage-related knee pain, only short-lived (\<30min) morning stiffness, functional limitation (based on yes/no to the following question: Is your functional level reduced as compared to before your knee symptoms first started?) and one or more typical examination findings (crepitus, restricted movement, bony enlargement). The presence of this cluster correctly diagnosed 99% of cases with KOA.

Exclusion Criteria:

* Less than mild functional limitations (a score above 75 on a 0-100 worst to best scale in the Spanish version of the self-report questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living (ADL) and quality of life (QOL).
* Previous knee replacement or any other lower limb surgery in the affected knee within the previous 3 months.
* Fracture of the affected extremity within the previous 6 months.
* Initiation of opioid analgesia or any form of injection (i.e. corticosteroid, hyaluronic acid, platelet-rich plasma) for knee pain within the previous 30 days.
* Physical impairments unrelated to the knee that would prevent safe participation in exercise.
* Any comorbidity that prevents from participating in the interventions (e.g.uncontrolled hypertension, moderate to high risk for cardiac complications)
* Any skin or medical condition preventing tactile stimulation on the knee.
* Inability to comprehend and complete study assessments or comply with study instructions (e.g. illiteracy, cognitive or visual impairments).
* Inability to a priori attend or complete the proposed course of intervention and follow-up schedule.