Low doses of naloxone produce analgesia in the mouse brain by blocking presynaptic autoinhibition of enkephalin release.
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 microgram/kg s.c. or 1 ng intracisternal) and hyperalgesia at higher doses (100 micrograms/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.
Ueda
H
H
Fukushima
N
N
Kitao
T
T
Ge
M
M
Takagi
H
H
D000698:Analgesia; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage*; D009433:Neural Inhibition / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009270:Naloxone; D004744:Enkephalin, Methionine