The analgesic effect of apelin-13 and its mechanism of action within the nitric oxide and serotonin pathways.

Background: Apelin has various effects on a lot of systems such as central nervous system and cardiovascular system. This study investigated the possible analgesic effects of apelin-13 using the hot-plate and the tail-flick thermal analgesia tests in rats. We also evaluated the mechanism underlying the analgesic effects of apelin-13 by pretreating with Nw-nitro-L-arginine methyl ester (L-NAME) or ondansetron.

Material & Methods: Forty male rats were used. The rats were randomly assigned to five groups according to the treatment received: Group I: Control; Group II: Morphine; Group III: Apelin-13; Group IV: Apelin-13+L-NAME; Group V: Apelin-13+Ondansetron. Acute thermal pain was modeled using the hot-plate and the tail-flick tests.

Results: During the hot-plate test, i.p. Morphine and apelin-13 administered at zero- and 30 min produced significantly greater analgesic effects compared to the control. When the nitric oxide pathway was inhibited by administration of L-NAME with apelin-13, the analgesic effect continued. When apelin-13 and ondansetron were co-administered, the analgesic effect of apelin-13 disappeared at zero- and 30 min. During the tail-flick test, at 30 min, significantly higher levels of analgesia were observed in both the morphine and apelin group (which did not differ from each other) compared to the control group. L-NAME co-administered with apelin-13 did not affect the degree of analgesia, but apelin-13 co-administered with ondansetron was associated with a greater reduction in analgesia compared to the other groups.

Conclusion: Our results demonstrate that apelin-13 exerts an analgesic effect; co-administration of apelin-13 and ondansetron inhibits antinociception, an effect apparently mediated by five-hydroxytryptamine-three (5-HT3) receptors. Hippokratia 2015; 19 (4): 319-323.