Evolution of Analgesic Tolerance and Opioid-Induced Hyperalgesia Over 6 Months: Double-Blind Randomized Trial Incorporating Experimental Pain Models

Contributors to the ongoing epidemic of prescription opioid abuse, addiction, and death include opioid tolerance, withdrawal symptoms, and possibly opioid-induced hyperalgesia (OIH). Thirty stable chronic nonmalignant pain patients entered a 6-month long, randomized, double-blind, dose-response, 2-center trial of the potent opioid levorphanol, conducted over a decade ago during an era of permissive opioid prescribing. Eleven were taking no...