ROLE OF HIGH OMEGA -6 DIET AS A RISK FACTOR FOR PAIN THROUGH INCREASED TRPV1 AND TRPA1 ACTIVITY

Physicians recommend dietary interventions for management of cardiovascular disease,diabetes and many autoimmune diseases; however, there is a large gap in knowledge on the role ofdiet as a risk factor or potential therapy for chronic pain. Management of pain remains a substantialmedical problem, in part, because of an incomplete understanding of the physiologic mechanisms fortransduction and processing of noxious stimuli. Moreover, current analgesics are often limited byincomplete efficacy, unacceptable side effects or risk of dependency. New discoveries for both thetreatment and prevention of chronic pain are essential, and investigating the relationship between dietand pain allows for the potential development of new therapies along with a better understanding of themechanisms of persistent pain. Multiple studies have demonstrated that oxidized metabolites of linoleic acid (LA) or arachidonicacid (AA) have potent biological actions in activating transient receptor potential (TRP) channels,including TRPV1 and TRPA1, that are expressed on nociceptive neurons. Since LA and AA areessential omega-6 polyunsaturated fatty acids (PUFA), their physiologic levels are a function of dietaryintake. Preliminary data presented in this application demonstrate that mice fed a 15-week highomega-6 diet exhibit changes in basal thermal and mechanical nociceptive thresholds and increasedresponses to noxious stimuli. However, there is still a large gap in knowledge as the mechanisms bywhich dietary omega-6 lipid intake modulate pain is not understood. Based on recent studies and ourpreliminary data, we propose to test the central hypothesis that increased dietary omega-6 PUFA leadsto increased thermal hyperalgesia and mechanical allodynia via increased TRPV1 and TRPA1activities. Diet-induced increased TRPV1 and TRPA1 activity could be a common mechanism amongmultiple chronic pain conditions and play a role in the transition from acute to chronic pain. Thefollowing aims will test the hypothesis:Specific Aim #1: Assess cellular lipid composition change following a 15-week high omega-6 diet anddetermine the role of the lipids in thermal and mechanical nociception.Specific Aims #2: Investigate the role of TRPV1 and TRPA1 in increased thermal and mechanicalnociception following a high omega-6 diet.Specific Aim #3: Determine whether high lipid diet alters nociception in a sex-specific manner.This study is innovative in its rationale and potential for identifying an environmental factor that couldpredispose and possibly predict pain response. This project may also lead to novel therapeuticapproaches for treatment and prevention of chronic pain conditions. Moreover, the techniques andresearch methods provide an ideal training vehicle for my career as an academic physician-scientist.