Preliminary data in chronic back pain patients showed no benefits of the treatment; we did not further pursue the same treatment in osteoarthritis patients.

In this study the investigators aim to examine the effects of Transcranial Magnetic Stimulation (TMS) on hippocampal network connectivity and pain levels in individuals with pain due to knee osteoarthritis.

Osteoarthritis (OA) pain is one of the most prevalent causes of chronic pain worldwide. Symptoms can last from months to a lifetime, severely impacting patients' quality of life. New strategies - including non-invasive brain stimulation techniques - have shown promise for sustained pain relief, yet evidence on their reliability and efficacy is limited. Apkarian et. al have previously shown that the dorsal hippocampus plays a central role in pain analgesia; thus, the study aim is to test whether non-invasively enhancing dorsal hippocampus activity is a useful new strategy for pain relief in knee OA patients. This study will recruit 35 patients with chronic OA pain for > 6 months. Each participant will receive 3 rounds of different treatment modalities in a cross-over manner. Each treatment modality will consist of 5 daily consecutive rTMS sessions followed by a 2-weeks wash-out period. Questionnaires will be completed prior to and following each intervention, and after each treatment round. Participants will be trained to use a pain electronic application (smartphone-based tool to rate pain intensity and mood on NRS scales, as well as indicate rescue medication use, developed in our lab). They will be asked to use this application for 7-10 days prior to the first round of intervention and during the study duration.

Inclusion Criteria:

• ≥ 6 months of knee pain on a daily basis;
• male or female with no racial or ethnic restrictions;
• 18 to 75 years old;
• average knee pain intensity > 4/10 at study entry;
• must be able to read, understand, and sign consent form;
• generally healthy.
• able to use the PainApp

Exclusion Criteria:

• rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures,
• Chronic neurologic conditions, e.g., Parkinson's
• other severe medical diseases;
• pregnancy;
• positive urinary screen for any recreational drugs,
• opioids use;
• use of anticoagulants (low dose ASA allowed);
• history of gastric ulcer; renal insufficiency or congestive heart failure,
• contraindication to MRI,
• contraindication to TMS; including history of seizure/epilepsy*
• Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk;
• In the judgment of the investigator, unable or unwilling to follow protocol and instructions.
• Diagnosis of major depression.