The proper control of acute and chronic pain is one of the most important areas of health care. Despite profound advances in neuroscience, opiate narcotics are heavily relied upon for postoperative pain control. This is problematic as opiates can sometimes lead to addiction and are associated with considerable side effects that are especially problematic in patients recovering from abdominal surgery, as they can directly hinder gut recovery, likely prolong hospital stay and delay recovery. Presently, there do not appear to be good replacement pharmacological candidates for postoperative pain control. Brain stimulation for pain control is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neuroanatomy of pain. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). Several studies have shown that TMS can reduce pain in healthy adults and patients with chronic pain. Recently, it was shown that a single 20-minute treatment of TMS over the left-prefrontal cortex (an area that is likely involved in inhibiting the affective dimension of pain) significantly reduced postoperative pain and patient-controlled analgesia (PCA) use by 37% among 40 patients immediately following gastric- bypass surgery. However, methodological concerns surrounding these preliminary findings limit definitive conclusions about the effectiveness of TMS in controlling post-operative pain. This R21 proposal will integrate more rigorous experimental conditions, a true double-masked methodology, and longer-term follow- up assessment. The data from this R21 will provide the information needed for launching a definitive larger- scale investigation into potential clinical applications and mechanisms of action of TMS in controlling post- operative pain. Using rigorous double-masked methods and building on preliminary pilot work, we propose (Aim1) to test whether repetitive transcranial magnetic stimulation over the left prefrontal cortex significantly reduces post-operative pain and PCA use following gastric-bypass surgery. We also propose (Aim2) to determine the effects of timing and dose of TMS on post-operative pain and PCA use. Lastly, (Aim3) we propose to determine the effects of TMS on post-surgical recovery time, clinical outcomes and healthcare costs at 1-month, 3-months and 6-months follow-up. 132 participants will be randomly assigned to receive 20 minutes of: active prefrontal TMS or sham prefrontal TMS 45-minutes after gastric-bypass surgery. Participants will then be re-randomized to receive a second treatment (either real or sham) 8 hours later. Participants'PCA usage will be tracked along with twice-daily visual analogue scale ratings of postoperative pain and mood. This design provides 4 conditions yielding information relevant to the effects of timing and dose of TMS on postoperative pain control and longer-term clinical outcomes. Results from this pilot will likely supply substantial information about the utility of cortical stimulation for pain postoperative control. PUBLIC HEALTH RELEVANCE: The proper control of acute and chronic pain is one of the most important areas of health care, and despite profound advances in neuroscience, opiate narcotics are heavily relied upon for postoperative pain control. There are many risks associated with opiate use including respiratory depression, nausea and vomiting, cough suppression, mental clouding, sedation and constipation, and many of these side-effects are particularly problematic in gastric-bypass surgery patients who tend to have respiratory problems (like obstructive sleep apnea), right ventricular dysfunction, pulmonary hypertension, and for whom post-operative vomiting could result in serious complications. Thus, new interventions that have the potential to reduce reliance on postoperative morphine in this patient population such as TMS need to be explored.