Antinociceptive effects of intrathecal endomorphin-1 and-2 in rats

Endomorphin-1 and endomorphin-2 were recently postulated to be endogenous m u-opioid receptor agonists. We have investigated the antinociceptive and an tihyperalgesic effects of intrathecally administered endomorphins in cumula tive doses (0.1-100 mu g) on acute and inflammatory pain sensations in awak e rats. In the tail-flick test, both peptides caused a dose-dependent short -lasting antinociception, except at the highest dose, which caused motor im pairment also. The dose-response curves revealed the development of acute t olerance (tachyphylaxis) to endomorphin. Similarly in the carrageenan-injec ted paw, the endomorphins (10 mu g) exerted transient antinociceptive effec ts. These are the first data to demonstrate decreased responsivity in model s of both acute and inflammatory pain after intrathecal administration of e ndomorphin-1 and -2 in awake rats.