Personalized Analgesia Through Central Nervous System Engagement to Unlock Performance

Using a double-blind, cross-over, 16-week randomized clinical trial of duloxetine versus placebo, this study will investigate whether duloxetine improves walking ability and physical activity in knee osteoarthritis patients (N=85). Aerobic exercise such as walking is important in preventing joint deterioration and is a first-line treatment for knee osteoarthritis, despite being painful. Indeed, many patients are limited in their ability to walk due to pain. Prior literature and preliminary data from our group indicate that central nervous system (CNS) pain processing contributes to pain-related walking impairment. While acetaminophen, nonsteroidal anti-inflammatories, opioids, and surgery are often used in knee osteoarthritis, side effects and health risks limit their use in many patient subgroups. In patients with CNS changes, these treatments may be less effective. In patients with nociplastic pain related to CNS sensitization, knee replacement is associated with worse post-operative pain and functional outcomes. Potentially targeting CNS sensitization, duloxetine is the only CNS-acting medication FDA-approved for knee osteoarthritis pain, and given that patient-reported physical function improves with duloxetine, its use may slow joint degeneration and delay the need for knee replacement by improving walking ability. However, no clinical trials have investigated whether duloxetine improves objectively measured physical function. This study will address this gap and lead to future large-scale studies examining knee osteoarthritis endophenotypes, related to CNS pain processing and other pathophysiology, which may aid in identifying patients who respond better to duloxetine versus other existing therapies. Techniques used in the setting of this randomized clinical trial include patient-reported outcomes, physical performance tests, actigraphy, noninvasive brain imaging, and quantitative sensory testing.