Modulation of pain by ketones: a mini-review

Abstract

Ketones, or ketone bodies, are organic molecules produced via ketogenesis in the liver in response to changing energy demands. Three ketones are generated that can act as metabolic messengers and a fuel source for the body, typically forming when glucose levels decrease within the bloodstream. A ketogenic diet, a form of low-carbohydrate, high-fat diet, stimulates ketogenesis and forces ketone utilization as an energy source by nonhepatic tissues. Currently, ketones, along with the ketogenic diet, have been of interest to many as a therapeutic mechanism for multiple conditions, including epilepsy, numerous neurodegenerative diseases, and diabetes. Emerging preclinical evidence suggests that ketones may play a powerful role in modulating acute and chronic pain. Here, we summarize the known benefits of ketones on neurological disease and nociceptive systems associated with pain. We discuss possible mechanisms identified from preclinical studies underlying the identified benefits of ketones in reducing pain.

Keywords: ketogenic diet; ketone; metabolism; mitochondria; pain.

Figure 1

presents neurological disorders that have shown improvement with a ketogenic diet.

Fig. 2

illustrates the range of known physiological benefits of ketones or a ketogenic diet in human and murine models.

Fig. 3

depicts proposed relationship between metabolic fluctuations and pain sensation. Pain-inducing drugs like bortezomib increase glycolysis in sensory neurons, shifting the metabolic balance. Ketones boost mitochondrial oxidative phosphorylation and reduce pain. Cellular metabolism in nociceptors may be a key component underlying the benefits of ketone body reduction in pain.