protectin-d1 and Neuralgia

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-PD1

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Chronic Disease; Diabetic Neuropathies; Docosahexaenoic Acids; Female; Injections, Intraperitoneal; Male; Mice; Mice, Inbred NOD; Molecular Structure; Neoplasms, Experimental; Neuralgia; Pruritus; Streptozocin

Prevalence of neuropathic pain is high after major surgery. However, effective treatment for preventing neuropathic pain is lacking. Here we report that perisurgical treatment of neuroprotectin D1/protectin D1 (NPD1/PD1), derived from docosahexaenoic acid, prevents nerve injury-induced mechanical allodynia and ongoing pain in mice. Intrathecal post-treatment of NPD1/PD1 also effectively reduces established neuropathic pain and produces no apparent signs of analgesic tolerance. Mechanistically, NPD1/PD1 treatment blocks nerve injury-induced long-term potentiation, glial reaction, and inflammatory responses, and reverses synaptic plasticity in the spinal cord. Thus, NPD1/PD1 and related mimetics might serve as a new class of analgesics for preventing and treating neuropathic pain.

Topics: Animals; Docosahexaenoic Acids; Mice; Neuralgia; Pain Measurement; Peripheral Nerve Injuries; Sciatic Nerve; Spinal Cord