We are conducting a nationwide study to compare treatments to reduce pain and improve function in people living with knee osteoarthritis. This large clinical trial will involve veterans, active military, as well as the general public. This study has two phases. Both phases compare different non-surgical treatments for knee osteoarthritis pain. You may be eligible for one or both phases. People who enroll in Phase 1 will be randomized, which is like drawing numbers from a hat, into one of three groups. The first group includes Best Practices for knee osteoarthritis like physical therapy, exercise, weight management, yoga, or over-the-counter medications. The second group, adds a medicine called duloxetine to the Best Practices. The third group adds a web-based program focused on enhancing pain coping skills to the Best Practices and the duloxetine. The second phase of the project involves randomization to a knee injection, radiofrequency ablation (which means local burning or cooling of the nerves through a small needle), or nerve blocks. Phase 1 of the study would require you to complete questionnaires and attend 3 study visits, which can be done either remotely or in person. Phase 2 of the study would require you to complete questionnaires and attend 4 study visits, some of which can be done remotely if you prefer. People in the study will also complete brief follow-up assessments either online or on the phone so we can better understand how long these treatments are effective. If you complete the brief screen below, our team will contact you to give you more information and see if you might be interested and eligible in participating. Study number: IRB00238678m. Principal Investigator: Steven Cohen.