Involvement of Vanilloid- and Cannabinoid Receptors in the Anti-inflammatory Action of Nociceptin

Abstract

In the present study, we have examined the probable interactions of N/OFQ(1-13)NH2 and its structural analogue [Orn 9]N/OFQ(1-13)NH2 with cannabinoid CB1-receptors on acute carrageenan (CG)-induced inflammation in rat paw, as well as the mechanism of these interactions. The study also aims to find out whether the TRPV1-receptors (transient receptor potential vanilloid 1) take part in these processes. Our results showed that the simultaneous treatment of rats with CB1-receptor agonist HU-210 and the investigated peptides did not change the specific effects of the nociceptin and [Orn]N/OFQ(113)NH2. Applied after blockade of CB1-receptors, the peptides did not exert their anti-inflammatory effects. On the contrary, when the TRPV1-receptors were blocked, the anti-inflammatory effects of nociceptin (NOP)-receptor agonists as a whole remained unchanged. In conclusion, based on the results obtained, it might be suggested that N/OFQ(1-13)NH2 and [Orn 9]N/OFQ(1-13)NH2 influenced the peripheral inflammation by interactions with their own NOP-receptors located on the primary sensory neurons. We also suppose that there is a functional link between NOPand cannabinoid CB1-receptors. It might be assumed that vacant or activated CB1-receptors are required for NOP-evoked inhibition of acute peripheral inflammation.