Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation

A series of double-blind, placebo-controlled clinical trials demonstrated t hat low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intr aligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediat ed by a local mechanism in the inflamed tissue, because subcutaneous admini stration of a 1.2 mg dose of morphine failed to elicit an analgesic respons e. In contrast, submucosal administration of 1.2 mg morphine or 50 mug fent anyl to the site of extraction of an impacted third molar after the onset o f acute pain failed to elicit an analgesic response despite demonstration o f a sensitive bioassay. These data indicate that peripheral opioid analgesi a can be evoked in a model of chronic, but not acute, inflammatory pain, su ggesting a temporal dependent mechanism needed for the expression of periph eral opiate analgesia during inflammation in humans.