Effects of Photobiomodulation and Topical Diclofenac on Inflammation and Pain in Knee Osteoarthritis (EPIC-KO)

Inclusion Criteria: * Clinically confirmed knee osteoarthritis (OA) based on the American College of Rheumatology (ACR) criteria with symptomatic pain for ≥ 3 months * Average knee-pain intensity ≥ 30/100 on both the Daily Symptom Diary (DSD) run-in and CATI * Age ≥ 50 years * Ability to give informed consent, attend visits, and complete ≥ 4 of 7 DSD entries pre-randomization * Capacity to perform all study tasks (Timed Up-and-Go, knee OA assessments, blood draw, questionnaires, etc) Exclusion Criteria: Systemic and Rheumatic Disease * Active systemic rheumatic condition (e.g., rheumatoid arthritis, systemic lupus erythematosus) * Fibromyalgia with pain outside the knee that is equal to or worse than knee pain Musculoskeletal History * Clinically significant surgery on the index knee (e.g., arthroplasty, osteotomy) * Knee surgery within the past 6 weeks * Intra-articular injection to the index knee within the past 14 days Medication Use * Daily opioid therapy * Hypersensitivity or allergy to diclofenac, other NSAIDs, or PBM * Use of centrally acting sodium-channel blockers or NMDA-receptor antagonists * New prescription or OTC analgesic, non-pharmacologic pain therapy, investigational drug, chemotherapy, or radiation therapy initiated ≤ 30 days before screening * Clinically significant drug interaction between topical diclofenac and concomitant medications per Drugs.com Drug Interaction Checker Cardiovascular Safety * Uncontrolled hypertension (SBP \> 150 mmHg or DB…