TY - JOUR T1 - Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions JF - bioRxiv DO - 10.1101/2020.05.15.077164 SP - 2020.05.15.077164 AU - Jacob T. Boyd AU - Peter M. LoCoco AU - Ashley R. Furr AU - Michelle R. Bendele AU - Meilinn Tram AU - Qun Li AU - Fang-Mei Chang AU - Madeline E. Colley AU - Dominic A. Arris AU - Erin E. Locke AU - Stephan B.H. Bach AU - Alejandro Tobon AU - Shivani B. Ruparel AU - Kenneth M. Hargreaves Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/16/2020.05.15.077164.abstract N2 - Chronic pain is the leading cause of disability worldwide1 and commonly associated with comorbid disorders2. However, the role of diet in chronic pain is poorly understood. Of particular interest is the Western-style diet, enriched with ω-6 polyunsaturated fatty acids (PUFAs) that accumulate in membrane phospholipids and oxidize into pronociceptive oxylipins3,4. Here we report that mice administered a diet enriched with ω-6 PUFAs develop persistent nociceptive hypersensitivities, spontaneously-active and hyper-responsive glabrous afferent fibers, and histologic markers of peripheral nerve damage reminiscent of a peripheral neuropathy. Linoleic and arachidonic acids accumulate in lumbar dorsal root ganglia, with increased liberation via elevated PLA2 activity. Pharmacological and molecular inhibition of PLA2g7 or diet reversal with high ω-3 PUFAs attenuate nociceptive behaviors, neurophysiologic abnormalities, and afferent histopathology induced by high ω-6 intake. In addition, ω-6 accumulation exacerbates the intensity or duration of allodynia observed in preclinical inflammatory and neuropathic pain models, as well as in clinical diabetic neuropathy. Collectively, these data reveal diet as a novel etiology of peripheral neuropathy and risk factor for chronic pain, and implicate multiple therapeutic considerations for clinical pain management.Competing Interest StatementThe authors have declared no competing interest. ER -