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5 Articles in this Series
Diet “Cheat” Days Negatively Impact Recovery From Inflammatory Injury
Ketogenic Diet Prevents and Rescues Mechanical Allodynia Induced by a High Fat Diet
Prolactin Linked to Sex Differences in Migraine
Toward Automated Pain Intensity Estimation in Mice: Finding Structure in Complex Data
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Ketogenic Diet Prevents and Rescues Mechanical Allodynia Induced by a High Fat Diet

Presentation by Michael Cooper, graduate student, working with Doug Wright, PhD

A high fat diet (55% fat) induces a prediabetic state in mice that is characterized by obesity, hyperglycemia, and mechanical allodynia, in which normally innocuous touch stimuli become painful.

Research from the University of Kansas has previously shown that voluntary wheel running does not prevent mechanical allodynia from developing in mice fed this diet, but the continued exercise does lead to a rescue of the mechanical allodynia after 6 weeks.1

Mice fed a ketogenic diet never develop mechanical allodynia despite increased body weight, fat mass, and blood glucose.

To better investigate how exercise was exerting this recovery effect in the setting of a high fat diet, the research team recently explored the consequences of increased fat metabolism using a ketogenic diet, which is very high in fat, moderate in protein, and extremely low in carbohydrates (90% fat, 9% protein, 1% carbohydrates). The virtual elimination of carbohydrates forces cells to switch their main energy source to fat,2 which the researchers hoped would prevent the development of mechanical allodynia entirely.

The new study,3 led by Doug Wright, PhD, was presented at this year’s meeting and selected as one of the meeting’s most promising abstracts by the Scientific Program Committee. It was presented by graduate student Michael Cooper as both a poster and a talk in a session on meeting highlights.

Wright and colleagues found that mice on the ketogenic diet (who were not allowed to exercise) and mice on the high fat diet who exercised developed similar metabolic changes after 12 weeks: increased body weight, fat mass, and blood glucose. The magnitude of these metabolic changes was greatest in the high-fat sedentary animals.

In contrast to mice fed a high fat diet that exercised, where mechanical allodynia was initially induced but then abolished, those on the ketogenic diet never developed mechanical allodynia in the first place. “This was surprising to us since the ketogenic animals did develop many of the poor metabolic factors that we saw in our other groups,” Cooper explained.

The researchers then performed an experiment where all animals received a high fat diet for 8 weeks to induce mechanical allodynia, and then were switched to either a control diet, a high fat diet with exercise, or a ketogenic diet without exercise.

The control diet was able to rescue the increased body weight, fat mass, insulin, and blood glucose that occurred from the high fat diet, but not the mechanical allodynia. In contrast, 4 weeks of the ketogenic diet did abolish the high fat diet-induced sensitivity to pain.

“In summary, the mice fed a traditional high fat diet developed mechanical allodynia, but the ketogenic animals, who received an even higher fat diet, did not. This tells us that it’s not just the intake of fat that drives the allodynia. We think that a sedentary lifestyl and poor diet is inducing a negative metabolic change in peripheral nerves that causes an increase in sensitivity. Using a diet that is still high in fat, but in a way that improves fat metabolism, provides an improved metabolic environment in the periphery that places these nerves in a less allodynic state,” Dr. Cooper said.



1.     Cooper MA, Ryals JM, Wu PY, Wright KD, Walter KR, Wright DE. Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation. J Peripher Nerv Syst. 2017;22(1):39-46.

2.     Branco AF, Ferreira A, Simões RF, Magalhães-Novais S, Zehowski C, Cope E, Silva AM, Pereira D, Sardão VA, Cunha-Oliveira T. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016;46(3):285-298.

3.     Cooper M, Ryals J, Wright D. A ketogenic diet prevents alterations in peripheral nerve function induced with a high-fat/carbohydrate diet. Poster presented at: Annual Meeting of the American Pain Society; May 17-20, 2017; Pittsburgh, PA. Poster #122.




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