A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice. Issue 12 (9th March 2021)

• Record Type: Journal Article
• Authors: Nesman, Jannicke Irina; Chen, Ouyang; Luo, Xin; Ji, Ru-Rong; Serhan, Charles N.; Hansen, Trond Vidar
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 12(2021)
• Page Start: 2744
• Page End: 2752
• Publication Date: 2021-03-09
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob02136a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The novel protectin D1 analog 3-oxa-PD1n-3 DPA was synthesized. Nanogram amounts of this analog reduces neuropathic pain and chronic itch, and shows analgesic action in a mouse model of diabetic neuropathy. Abstract : 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 enzymatically oxygenated polyunsaturated fatty acids belong to distinct families of specialized pro-resolving autacoids. The protectin family of mediators has attracted an interest because of their potent pro-resolving and anti-inflammatory actions verified in several in vivo disease models. Herein, we present the stereoselective synthesis and biological evaluations of 3-oxa-PD1n-3 DPA, a protectin D1 analog. Results from mouse models indicate that the mediators protectin D1, PD1n-3 DPA and the new analog 3-oxa-PD1n-3 DPA all relieved streptozotocin-induced diabetic neuropathic pain at doses of 90 and 300 pmol, equivalent to 30 and 100 ng, respectively, following intrathecal (I.T.) injection. Of interest, at a low dose of only 30 pmol (10 ng; I.T.) only 3-oxa PD1n-3 DPA was able to alleviate neuropathic pain, directly compared to vehicle controls. Moreover, using a chronic itch model of cutaneous T-cell lymphoma (CTCL), all three compounds at 300 pmol (100 ng) showed a significant reduction in itching for several hours. 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.