Recent research suggests a role for
ghrelin in the modulation of inflammatory disorders. However, the type of
ghrelin receptor (GHS-R) involved in both the anti-inflammatory and anti-hyperalgesic actions of
ghrelin remains to be characterized. In this study, we examined whether the inhibitory effect of
ghrelin in the development of
hyperalgesia and
edema induced by intraplantar
carrageenan administration depends on an interaction with
GHS-R1a. Both central (1 nmol/rat, i.c.v.) and peripheral (40 nmol/kg, i.p.) administration of the selective
GHS-R1a agonist
EP1572 had no effect on
carrageenan-induced
hyperalgesia measured by Randall-Selitto test and paw
edema. Furthermore, pre-treatment with the selective
GHS-R1a antagonist, D-lys(3)-GHRP-6 (3 nmol/rat, i.c.v.) failed to prevent the anti-hyperalgesic and anti-inflammatory effects exerted by central
ghrelin administration (1 nmol/rat), thus indicating that the type 1a GHS-R is not involved in these
peptide activities. Accordingly, both central (1 and 2 nmol/rat, i.c.v.) and peripheral (40 and 80 nmol/kg, i.p.) administration of
desacyl-ghrelin (DAG), which did not bind
GHS-R1a, induced a significant reduction of the hyperalgesic and edematous activities of
carrageenan. In conclusion, we have shown for the first time that DAG shares with
ghrelin an inhibitory role in the development of
hyperalgesia, as well as the paw
edema induced by
carrageenan and that a
ghrelin receptor different from type 1a is involved in the anti-inflammatory activities of the
peptide.