Clinical Perspective Acute postoperative pain remains a significant medical problem. Patients undergoing outpatient ambulatory surgery have clinically significant postoperative pain even when administration of oral opioids and nonopioid adjuncts are optimized [1]. Regional analgesic techniques improve pain control except their use is limited to a minority of all surgical patients [8; 31]. For those patients undergoing major surgical procedures, ongoing pain or pain at rest, and pain during activities are important clinical symptoms. Pain at rest is usually moderate; the average visual analogue pain scale (VAS) is 3 to 4 out of 10 during the first 2 to 3 days after surgery [24]. These pain scores occur even when parenteral treatments are administered. Usually, pain at rest resolves within the first week after surgery (see schematic, Fig. 1). Pain with activities, such as coughing or walking is severe during the first 2 to 3 days; the average visual analogue scale can be as great as 7 to 8. Pain with activities is moderate or severe for many days and even weeks later. Functional capability is limited during this period as well; thus, pain can be moderate and the activities like ability to cough or walking distance to evoke this pain are reduced [16; 36]. Greater opioid dosing to further reduce pain is limited by side effects like nausea, vomiting, ileus, respiratory depression and sedation [8]. Figure 1 Schematic of postoperative pain after major surgery in patients with optimized parenteral opioid analgesia. Top line is pain with cough; bottom line is pain at rest. VAS=visual analogue scale. Clinically, our goal is to advance simple, safe, effective therapies that will greatly reduce postoperative pain. In the last 10 to 15 years, gabapentinoids and cyclooxygenase-2 inhibitors have been trialed extensively and regional anesthesia is advancing in acceptance [9] In general, we have had difficulty making major improvements in the overall treatment of clinical postoperative pain for the majority of patients.