Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates...

Area of Science:

• Neuroscience
• Nutrition Science
• Pathology

Background:

• Chronic pain is a global health issue linked to other disorders.
• The impact of diet, especially the Western diet rich in omega-6 polyunsaturated fatty acids (PUFAs), on chronic pain is not well understood.
• Omega-6 PUFAs can oxidize into pronociceptive oxylipins, potentially contributing to pain.

Purpose of the Study:

• To investigate the role of omega-6 PUFA-enriched diets in the development of chronic pain and peripheral neuropathy.
• To explore the mechanisms by which omega-6 PUFAs affect nerve function and pain signaling.
• To identify potential dietary interventions for managing chronic pain.

Main Methods:

• Mice were fed an omega-6 PUFA-enriched diet.
• Neurophysiological and histological assessments were performed to evaluate nerve function and damage.
• Levels of linoleic and arachidonic acids in dorsal root ganglia were measured.
• The activity of phospholipase A2 (PLA2) was assessed.
• Pharmacological and molecular inhibition of PLA2G7 and dietary interventions were employed.
• Allodynia was evaluated in preclinical pain models and correlated with clinical diabetic neuropathy data.

Main Results:

• Mice on an omega-6 PUFA-enriched diet developed persistent pain hypersensitivity, spontaneous afferent fiber activity, and nerve damage.
• Linoleic and arachidonic acids accumulated in dorsal root ganglia, with increased PLA2 activity.
• Inhibition of PLA2G7 or supplementing with omega-3 PUFAs reversed pain behaviors and nerve abnormalities.
• Omega-6 PUFA accumulation worsened pain in inflammatory and neuropathic models and correlated with diabetic neuropathy pain indices.

Conclusions:

• Dietary enrichment with omega-6 PUFAs is a novel cause of peripheral neuropathy and a risk factor for chronic pain.
• Elevated PLA2 activity plays a key role in omega-6 PUFA-induced neuropathy.
• Modulating omega-3 and omega-6 PUFA balance and inhibiting PLA2G7 show therapeutic potential for chronic pain management.