The Effects of the Ketogenic Diet and Estrous Stage on Inflammatory Pain in Female Mice

Chronic pain is highly prevalent within the United States, affecting an estimated 20.4% of the adult population. Growing evidence suggests that inflammation underlies many chronic pain disorders. A treatment that reduces inflammation, particularly without the use of pharmaceuticals, could be valuable for alleviating chronic pain states. The ketogenic diet (KD), characterized by high fat, moderate protein, and low carbohydrate intake, has traditionally been prescribed to reduce the severity and frequency of epileptic seizures. However, it has been proposed that the efficacy of the KD is due to its anti-inflammatory properties. Previous research within our lab has confirmed that KD treatment significantly reduces tactile allodynia in male mice. In the present study, we evaluated the effect of the KD on inflammatory pain in female mice. We also assessed whether estrous cycling affects pain sensitivity. Young adult female mice of cycling age (6-8 weeks of age) were assigned to KD or control diet (CD) treatment. After three weeks of dietary treatment, complete Freund’s adjuvant (CFA) was injected into the right hindpaw to induce sub-chronic inflammation and resulting tactile hypersensitivity. The left hindpaw served as a control. Electronic von Frey was performed at specified timepoints pre- and post-CFA injection to assess plantar tactile sensitivity. Estrous samples were collected on each day of behavioral testing. Two days after CFA treatment, both KD and CD female mice had returned to baseline sensitivity. KD mice exhibited a generalized decrease in tactile sensitivity, independent of time and paw treatment. Stage of estrous at time of CFA injection was not found to significantly affect tactile sensitivity. Further research is needed to characterize the difference in KD effects on inflammatory pain between female and male mice