Antinociceptive effect of centrally administered endothelin-1 and endothelin-3 in the mouse

The antinociceptive effects of centrally administered (i.c.v.) endothelin-1 (ET-1) and endothelin-3 (ET-3) were studied in mice by the use of 3 experimental procedures: hot plate, tail flick and acetic acid writhing tests. ET-1 (0.625-5 pmol/mouse) and ET-3 (2.5-25 pmol/mouse) produced statistically significant increase of the hot plate and tail flick latencies with duration of about 120 min. ET-3 showed weaker antinociceptive effect. ET-1 inhibited acetic acid-induced writhings with ED50 = 1.9 (1.1-2.7) pmol/mouse. With ET-3 a maximum effect of 45.2% suppression of the writhing response was achieved at 5 pmol/mouse. The antinociception due to ET-1 and ET-3 was not antagonized by naloxone and is thus independent of endogenous opioid release.