SPINAL ANALGESIC ACTIONS OF THE NEW ENDOGENOUS OPIOID-PEPTIDES ENDOMORPHIN-1 AND ENDOMORPHIN-2

Two highly-selective mu-opioid receptor agonists, endomorphin-1 and -2 , were recently purified from bovine brain and are postulated to be en dogenous mu-opioid receptor ligands. We sought to determine the effect s of these ligands at the spinal level in mice. Endomorphin-1 and -2 p roduced short acting, naloxone-sensitive antinociception in the tail f lick test and inhibited the behavior elicited by intrathecally injecte d substance P. Both endomorphin-1 and -2 were anti-allodynic in the dy norphin-induced allodynia model. Although acute tolerance against both endomorphins developed rapidly, endomorphin-1 required a longer pretr eatment time before tolerance was observed. We conclude that the endom orphins are potent spinal antinociceptive and anti-allodynic agents an d that they or related compounds may prove therapeutically useful as s pinal analgesics.