The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms

Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of omega-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. Methods: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received omega-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. Results: The results of the present trial showed that omega-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of omega-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). Conclusion: These findings indicate that combination therapy of omega-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.