Ketogenic diet effects on inflammatory allodynia and ongoing pain in rodents

David N Ruskin,Livia S Wyss,Isabella C Sturdevant,Susan A Masino

doi:10.1038/s41598-020-80727-x

Abstract

Ketogenic diets are very low carbohydrate, high fat, moderate protein diets used to treat medication-resistant epilepsy. Growing evidence suggests that one of the ketogenic diet’s main mechanisms of action is reducing inflammation. Here, we examined the diet’s effects on experimental inflammatory pain in rodent models. Young adult rats and mice were placed on the ketogenic diet or maintained on control diet. After 3–4 weeks on their respective diets, complete Freund’s adjuvant (CFA) was injected in one hindpaw to induce inflammation; the contralateral paw was used as the control. Tactile sensitivity (von Frey) and indicators of spontaneous pain were quantified before and after CFA injection. Ketogenic diet treatment significantly reduced tactile allodynia in both rats and mice, though with a species-specific time course. There was a strong trend to reduced spontaneous pain in rats but not mice. These data suggest that ketogenic diets or other ketogenic treatments might be useful treatments for conditions involving inflammatory pain.

Highlights

Ketogenic diets are very low carbohydrate, high fat, moderate protein diets used to treat medicationresistant epilepsy
All rats demonstrated strong allodynia of the injected hindpaw; the magnitude of this effect was significantly smaller at 4 h post-injection in ketogenic diet (KD)-fed animals (Fig. 2)
We found that treatment with a KD significantly ameliorated complete Freund’s adjuvant (CFA)-induced tactile allodynia in two model species, with more modest effects on indices of ongoing spontaneous pain

Summary

Introduction

Ketogenic diets are very low carbohydrate, high fat, moderate protein diets used to treat medicationresistant epilepsy. There is growing evidence that the ketogenic diet (KD) is anti-inflammatory This diet was introduced as an anticonvulsant treatment for drugrefractory epilepsy, and has very low carbohydrate content as a means to induce a metabolic state similar to fasting but without caloric restriction. KD treatment reduces reactive oxygen species[17,18,27,28,29,30,31,32], limits oxidative damage to D NA17,20,33, lipids[29,34,35,36,37], and p roteins[16,20,23,35], and modulates immune cell function[28,38] Most of these studies did not use a calorie-restricted KD. We tested a KD in a rodent model of experimental inflammatory pain, investigating allodynia and measures of spontaneous pain

Methods

Results

Conclusion