Low doses of naloxone produce analgesia in the mouse brain by blocking presynaptic autoinhibition of enkephalin release

Abstract

The involvement of presynaptic autoinhibition of Met-enkephalin release in naloxone-induced analgesia was studied. In both acetic acid writhing and tail-flick tests in mice, naloxone produced biphasic effects, analgesia at very low doses (1 μg/kg s.c. or 1 ng intracisternal) and hyperalgesia at higher doses (100 μg/kg s.c. or 100 ng intracisternal). Morphine at 10⁻⁶ to 10⁻⁵ M depressed the high K⁺-evoked release of Met-enkephalin from slices of the rat brainstem by 12.5–55.9% of control, while naloxone at 10⁻⁶ M significantly enhanced the release by 80.6%. These findings strongly suggest that in the mouse brain a very low dose of naloxone produces analgesia by blocking autoinhibition of enkephalin release.