Physiological relevance and time course of a tonic endogenous opioid modulation of nociceptive messages, based on the effects of naloxone in a rat model of localized hyperalgesic inflammation.

In a rat model of localized hyperalgesic inflammation induced by intraplantar injection of carrageenin, the effect of a relatively high dose of naloxone (1 mg/kg i.v.) was investigated using the measure of the vocalization threshold as a nociceptive test, on both the inflamed and non-inflamed paws. The effects of the drug were determined at two different periods after the intraplantar injection of carrageenin, in the same group of rats. We showed that 4 h after carrageenin (a few hours after the onset of the inflammatory process), naloxone induced a significant further decrease in the vocalization threshold induced by pressure on either paw, suggesting that naloxone had reduced a tonically active inhibitory system involving endogenous opioid peptides. Twenty-four hours after carrageenin, a consistent hyperalgesic effect of naloxone was observable only in rats which had recovered from their carrageenin-induced hyperalgesia. A significant negative correlation between the behavioral effect of naloxone and the degree of hyperalgesia determined for each animal was observed. This suggests that the tonic inhibition exerted by the endogenous opioids was particularly effective in rats which recovered from their initial hyperalgesia. By contrast, these opioid controls could have been weaker in those rats which remained hyperalgesic.