A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice

The resolution of inflammation is a biosynthetically active process controlled by the interplay between oxygenated polyunsaturated mediators and G-protein coupled receptor-signaling pathways. These oxygenated polyunsaturated fatty acids belong to distinct families of specialized pro-resolving autacoids. The protectin family of mediators has attracted a great interest due to their potent pro-resolving and anti-inflammatory bioactions verified in several in vivo disease models. Herein, stereoselective synthesis and biological evaluations of 3-oxa-PD1n-3 DPA, a protectin D1 analog, is presented. Results from mouse models showed that the mediators protectin D1, PD1n-3 DPA and the new analog 3-oxa-PD1n-3 DPA all relieved streptozotocin-induced neuropathic pain. Moreover, using a chronic itch model of cutaneous T-cell lymphoma (CTCL), all three compounds showed a significant reduction in itching at one and three hours. Of interest, after five hours, the ameliorating actions of 3-oxa PD1n-3 DPA and PD1 were as significant, directly compared to vehicle controls. The biomolecular information on the structure-functions of the protectins and the new synthetic analog 3-oxa-PD1n-3 DPA is of interest towards developing new immunoresolvents.