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 DBP \> 95 mmHg) * Unstable or activity-limiting cardiovascular or peripheral arterial disease Neurological and Psychiatric Conditions * Diagnosed neurological disorder (e.g., Parkinson's disease, multiple sclerosis, epilepsy) * History or evidence of stroke or moderate-severe traumatic brain injury * Serious psychiatric illness requiring hospitalization within the past 12 months * Active suicidal ideation * Current substance-use disorder or past hospitalization for substance-use treatment Dermatologic Conditions * Compromised skin integrity at or near the treatment site (e.g., open wounds, active rash, dermatitis, burns, ulcers, eczema, infection) interfering with topical treatment or PBM Renal Function * Severe renal impairment * History of acute kidney injury within the past 6 months Hepatic Function * Active liver disease or elevated liver enzymes * Known moderate to severe hepatic impairment * Acute or chronic liver disease such as hepatitis Other Metabolic Conditions * Uncontrolled diabetes * Diabetes-related complications (e.g., peripheral neuropathy, severe nephropathy, chronic ulcers at treatment site) * Active peptic ulcers or history of recurrent peptic ulcers with complications (e.g., bleeding, perforation) * Current use of anticoagulants with a history of gastrointestinal ulceration Other Pain Conditions * Chronic pain at another body site more severe than knee pain General Health and Cognition * Severe circulatory disorder * Pregnancy or lactation * Cognitive impairment that precludes informed consent or task participation