A Randomized Pilot rTMS Trial for Knee Arthritis Pain and Depression

Osteoarthritis (OA) is a major public health problem, and involvement of the knee is especially disabling. Symptomatic knee OA has an incidence rate between 40 to 1,020 per 100,000 person years1 and is among the most common causes of disability worldwide. Knee arthritis pain and disability are highly comorbid wiht depression (30-50%). Currently available treatments offer only limited relief. The Pilot project aims to establish feasibility of the rTMS neuromodulation of response to Tai Chi and improvement in pain and comorbid depression in patients with knee OA. There are several ways in which the pilot project will improve scientific knowledge, and clinical practice: 1) The sequential stimulation of two targets (M1 and l-DLPFC) has not been systematically examined for the treatment of comorbid MDD and knee OA. We hypothesize that using a multi-target rTMS strategy combining M1 and l-DLPFC- active targets will be well tolerated and more effective to treat comorbid symptoms than single site rTMS to M1+l-DLPFCsham. This hypothesis will be tested in Aim 1 of this proposal by comparing two experimental conditions: A) M1active and l-DLPFCactive; and B) M1active and l-DLPFCsham. 2) Identifying the relationship between improvement in pain and depression to improvement in pro-inflammatory cytokines would be novel. Adding an rTMS as a neuromodulation technique with novel stimulation sites to assist in the reduction of symptoms of pain and depression is another scalable to clinical use opportunity that will provide pilot data for future clinical trials. We will perform a pilot feasibility trial of rTMS for those presenting with knee osteoarthritis related pain and moderate to severe depression in 30 volunteers who are undergoing Tai Chi intervention. Tolerability and safety of rTMS added to Tai Chi will be assessed along with changes in symptoms of pain and depression, in preparation to future R-01 applications.