Abstract
Chronic pain is the leading cause of disability worldwide and is commonly associated with comorbid disorders. 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 oxidise into pronociceptive oxylipins. Here we report that mice administered an ω-6 PUFA-enriched diet develop persistent nociceptive hypersensitivities, spontaneously active and hyper-responsive glabrous afferent fibres 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 phospholipase (PLA)2 activity. Pharmacological and molecular inhibition of PLA2G7 or diet reversal with high levels of ω-3 PUFAs attenuate nociceptive behaviours, neurophysiologic abnormalities and afferent histopathology induced by high ω-6 intake. Additionally, ω-6 PUFA accumulation exacerbates allodynia observed in preclinical inflammatory and neuropathic pain models and is strongly correlated with multiple pain indices of clinical diabetic neuropathy. Collectively, these data reveal dietary enrichment with ω-6 PUFAs as a new aetiology of peripheral neuropathy and risk factor for chronic pain and implicate multiple therapeutic considerations for clinical pain management.
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Key Points
This study assesses the potential for omega-6 fats’ influence on neuropathic pain in people with diabetes and other conditions. The effects of omega-6 fatty acids were measured in pain conditions and found that omega-6 cause pain and inflammation. The abundance of omega-6 polyunsaturated fats prominent in the typical Western diet served as a significant risk factor for both inflammatory and neuropathic pain in both mice and humans.
While both omega-6 and omega-3 fats are essential for proper nutritional health, the new study suggests that the preponderance of the former could have detrimental effects. This five-year study found that Western diets associated with obesity are characterized by much-higher levels of those omega 6 acids than healthy omega-3 fats, which are found in fish and sources like flaxseed and walnuts. Generally, unhealthy foods high in omega-6 fats include processed snacks, fast foods, cakes, and fatty and cured meats, among others. Reversing those dietary habits and increasing omega-3 fats greatly reduced these pain conditions. It was also demonstrated that skin levels of omega-6 lipids in patients with Type 2 diabetic neuropathic pain were strongly associated with reported pain levels and the need for taking analgesic drugs.