Aims: 

The objective of the present work was to determine the antinociceptive effects of peripheral versus central administration of the selective m-opioid agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO) and morphine in the rat writhing test.

Methods: 

Male Wistar rats weighing 100–140g were used. Visceral nociception (abdominal muscle contractions or simultaneous stretching of at least one hind limb) was induced by intraperitoneal (i.p.) injection of 2% acetic acid (3ml/kg). Saline or test substance (DAMGO or morphine) were injected (i.p. or i.c.v.) 55 min after i.p. acetic acid injections. Then, a period of 60–80min was used to asses the antinociceptive effect of the test compounds.

Results: 

i.p. and i.c.v. injections of DAMGO or morphine dose-dependently inhibited the rat visceral nociceptive responses. DAMGO and morphine showed comparable antinociceptive effect after i.p. application. However, DAMGO and morphine produced higher effects after i.c.v. than after i.p. administration, though the i.p./i.c.v. ratio for DAMGO was higher than that of morphine. Co-administration of the peripherally restricted opioid antagonist naloxone methiodide (NAL-M) significantly reversed the antinociceptive action of i.p. DAMGO and morphine. On the other hand, i.c.v. injections of NAL-M partially antagonized the antinociceptive effects of i.p. morphine, but did not influence the antinociceptive effect of i.p. DAMGO. Finally, i.p. injections of opioid antagonist naloxone totally blocked the antinociceptive effects of DAMGO or morphine.

Conclusions: 

The results presented here indicate that morphine produced visceral antinociception most likely through activation of both central and peripheral opioid systems. However, the antinociceptive effect of DAMGO is based mainly on the activation of the peripheral opioid system.

Support: 

OTKA (K-60999) and ETT (374/09)