Rowbotham MC, et al. - A randomized, double-blind, dose-response feasibility study in patients with chronic pain was reported. This trial was completed over a decade ago, but its results are particularly applicable in today's opioid prescribing climate. This trial was conducted to assess if, subsequent to 5 weeks of titration, opioid analgesic tolerance and opioid-induced hyperalgesia (OIH) emerge during 20 weeks of stable dosing. In this 6-month long, randomized, double-blind, dose-response, two-center trial, 30 stable chronic non-malignant pain patients were included. At study entry, 11 were taking no opioids and 11 were taking between 35-122 morphine equivalents. Five weeks titration was done prior to 20 weeks of stable dosing. The individual judgment of tolerance and OIH was done based on chronic pain ratings, Brief Pain Inventory scores, and results of the Brief Thermal Sensitization (BTS) model at five opioid dosing sessions. In this study, there was a decrease in pain at the end of the dose titration phase. However, opioid analgesic tolerance was observed in 10 of 17 completing patients - all initial benefit was lost by the end of 20 weeks of stable dosing. In fact, in the end, 8 of 17 completing patients had greater pain intensity scores than those observed at study entry, implying possible tolerance and OIH. Overall, small benefit was evident, and 18% of patients exhibited both tolerance and OIH. This work yielded critically relevant data for clinically defining analgesic tolerance and OIH.