Effect of d-arginine on antinociception induced by kyotorphin, Tyr-Cav, L-Cav and Tyr(Cl2)-Cav in rats

Kyotorphin (Kyo) is synthesized in specific brain regions where it may modulate synaptic transmission. Kyo directly excites cortical neurons, and indirectly exerts opioid actions to produce analgesia via the release of [Met]-enkephalin. Kyo is formed by a specific enzyme from L-tyrosine, L-arginine (L-arg) and ATP in the presence of Mg2+. Kyo and its analogues Tyr-cav and Tyr(Cl2)-cav exert naloxone-reversible antinociception in the paw-pressure test. The aim of the present study was to investigate the effect of D-arginine (D-arg) on the analgesic effects of Kyo, Tyr-cav and Tyr(Cl2)-cav during acute pain. The changes in the nociceptive effects were examined in male Wistar rats using the tail flick (TF) and hot plate (HP) tests. Kyo, Tyr-cav, Tyr(Cl2)-cav, L-canavanine (L-cav) and D-arg were applied in rats intracerebroventricularly (i.c.v.) at a dose of 20 μg/20 μl. Kyo, Tyr-cav, Tyr(Cl2)-cav and L-cav exerted antinociceptive activity in both tests used. Applied alone, D-arg had no antinociceptive activity in TF and HP tests. D-arg decreased the TF and HP latency of the Kyo, Tyr-cav, Tyr(Cl2)-cav and L-cav. Taken together, these results reveal D-arg as a potential inhibitor of the investigated peptides during acute pain.