Opioid analgesia at peripheral sites: a target for opioids released during stress and inflammation?

The peripheral analgesic effects of opiates were evaluated in a rat model of inflammation. The experimental design excluded a potential central nervous system site of action for the observed analgesia. After the injection of carrageenan (CARRA) in the plantar surface of both hind paws, an opiate was injected into one paw and saline was injected into the other paw. The inflamed paws injected with the μ-agonist, fentanyl (0.3 μg) or the ≃-agonist, ethylketocyclazocine (10 μg) were significantly less hyperalgesic (P < 0.001 and P < 0.01, respectively) than were the contralateral inflamed paws injected with saline. At these doses, fentanyl and ethylketocyclazocine were devoid of systemic effects. Another μ-agonist, levorphanol (20, 40, 80, or 160 μg) and dextrorphan (160 μg), its dextrorotatory isomer, were used next to evaluate opioid specificity. Levorphanol produced a dose-related blockade of CARRA-induced hyperalgesia (P < 0.005). In contrast, 160 μg of dextrorphan was inactive. These results demonstrate that local administration of opiates into an inflamed paw produces a dose-related, stereospecific analgesia restricted to the injected area.