Personalized Analgesia Through Central Nervous System Engagement to Unlock Performance

Inclusion Criteria: * Knee pain for greater than 6 months. * Moderate-to-severe knee pain (\>3/10) due to osteoarthritis, as defined by American College of Rheumatology and EULAR diagnostic criteria (Zhang 2010, Altman 1986) on \>50% of days in the past month. * KL grade 2-4 (Kellgren and Lawrence 1957) indicating significant degenerative changes on knee X-ray. This will be determined on evaluation of weight-bearing clinical X-rays on review of medical records. In the infrequent situation that the patient does not have an X-ray on review of their medical records, then the patient will obtain weight-bearing knee X-rays as part of the Screening Visit. * Age: 45-80 years old * Gender: Males and females will be recruited. * Language: only English-speaking subjects will be included. Exclusion Criteria: * Inflammatory arthritis (e.g. rheumatoid arthritis). * More intense pain due to another chronic pain syndrome (e.g. fibromyalgia, hip osteoarthritis) * Significant pain or weakness in the lower extremities due to a neurological condition (e.g. lumbar radiculopathy, paresis due to stroke) * New, ongoing acute pain * Recent use of duloxetine defined as any use within the last 3 months * Current use of antidepressants or tramadol * Current routine use of more than 30 mg oral morphine equivalents per day (use of \<=30 mg OME does not exclude the participant). * New treatment that may help knee osteoarthritis (including medication, exercise, behavioral, or complementary and integrative treatments) started in the last month. Stable use of treatments for greater than 1 month does not exclude the participant. * Unwillingness to maintain current knee osteoarthritis treatments for the duration of the study. This means that eligible participants must plan for the following: medications and dietary supplements should not change substantially in frequency or dose; behavioral therapy, exercise therapy, and complementary and integrative therapies should be consistent; and there should be no interventional treatments planned for lower extremity musculoskeletal conditions (e.g. joint steroid injections, knee radiofrequency ablation, knee replacement surgery). * Recent knee intra-articular injection of steroid or other agent (greater than 1 month does not exclude the participant) * Recent knee radiofrequency ablation (greater than 3 months does not exclude the participant) * Recent knee arthroscopic surgery (greater than 3 months does not exclude the participant) * History of kne…