reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet减少疼痛和炎症在少年和成年老鼠喂食生酮饮食.pdfVIP

Reduced Pain and Inflammation in Juvenile and Adult Rats Fed a Ketogenic Diet 1 1,2 1 David N. Ruskin , Masahito Kawamura, Jr. , Susan A. Masino * 1 Department of Psychology and Neuroscience Program, Trinity College, Hartford, Connecticut, United States of America, 2 Department of Pharmacology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Abstract The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3–4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund’s adjuvant- induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature) as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdr