Dissociated Effects of Inhibitors of Enkephalin-metabolising Peptidases or Naloxone on Various Nociceptive Responses

The antinociceptive effects of Thiorphan, an 'enkephalinase' inhibitor, or bestatin, an aminopeptidase inhibitor, as well as of their association and the pronociceptive effects of naloxone, an opiate receptor antagonist, were evaluated in various analgesic tests in mice. These tests could be classified into two groups: (i) those tests in which the two peptidase inhibitors display naloxone-sensitive antinociceptive activity, particularly when administered together, and in which naloxone displays pronociceptive activity (vocalisation, hot-plate jump, writhing), (ii) those tests in which the two peptidase inhibitors and naloxone are ineffective (tail withdrawal, hot-plate licking, tail-flick). In contrast to the above, either morphine or [Met5]enkephalin in subthreshold dosage administrated together with the peptidase inhibitors displayed antinociceptive activity in the two groups of tests. The threshold dosages of morphine were the lowest in tests of the first group. The dissociated and opposite effects of peptidase inhibitors and naloxone per se might reflect a variable participation of endogenous enkephalins (or other opioid peptides) in the control of various nociceptive responses.