A great unmet need exists for pain therapies that are non-addictive and/or address pain that remains intractable to treatments available currently. Opiates, the most powerful drugs to treat pain, pose serious side effects and addictive potential; on the other hand, non-steroidal anti- inflammatory drugs (NSAIDs) are often ineffective in some types of pain. There is emerging evidence to suggest that ketogenic diets may alleviate pain. A ketogenic diet is a regimen that is high in fat and low in carbohydrates, like a strict Atkins diet. The carbohydrate restriction decreases glucose metabolism and promotes use of ketone bodies as energy in tissues such as brain and spinal cord, which induces a metabolic shift in those tissues. The ketogenic diet has shown proven clinical efficacy in epilepsy, even drug-refractory epilepsy, for many decades and demonstrated basic research potential for neuroprotection in several types of acute and chronic brain injuries and neurodegenerative conditions. A number of biochemical consequences of ketogenic diets all suggest that a ketogenic diet will be effective in elevating pain thresholds and reducing inflammatory pain. Our recent work shows that a ketogenic diet can reduce inflammation and reduce sensitivity to thermal pain in male rodents. Unfortunately, little work exists on this topic in female people or rodents, who/which have different pain sensitivity and different responses to analgesics than males; in addition, these variables change across the menstrual/estrous cycle. Our central hypothesis is that ketogenic diets will alleviate pain, particularly inflammatory pain, in female rodents in an estrous cycle stage-dependent manner. The present objective is to test the effects of ketogenic diets in acute pain (nocifensive behavior regarding heat;
Specific Aim 1), acute inflammatory pain (nocifensive behavior regarding intraplantar formalin;
Specific Aim 2), and persistent inflammatory pain (tactile allodynia and other behaviors after intraplantar complete Freund?s adjuvant;
Specific Aim 3) while monitoring estrous cycle stage and studying any effects of the ketogenic diet on characteristics of the estrous cycle itself. Testing our hypothesis in well-established animal models is feasible and may yield new therapeutic opportunities for pain relief and a new avenue for developing pain treatments that are both effective and non-addictive.
Pain is common and debilitating, often without adequate treatment options and sometimes involving drugs with addictive potential. Evidence suggests that an established treatment for epileptic seizures ? a low carbohydrate ketogenic diet ? can provide relief in acute pain and inflammatory pain. This proposal will determine the effectiveness of a ketogenic diet in female rodents in well-characterized models of acute and inflammatory pain, identifying variations in pain sensitivity and ketogenic diet effectiveness across the estrous cycle.
| Elamin, Marwa; Ruskin, David N; Masino, Susan A et al. (2018) Ketogenic Diet Modulates NAD+-Dependent Enzymes and Reduces DNA Damage in Hippocampus. Front Cell Neurosci 12:263 |
| Ruskin, David N; Fortin, Jessica A; Bisnauth, Subrina N et al. (2017) Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse. Physiol Behav 168:138-145 |
| Ruskin, David N; Murphy, Michelle I; Slade, Sierra L et al. (2017) Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder. PLoS One 12:e0171643 |
| Kawamura, Masahito Jr; Ruskin, David N; Masino, Susan A (2016) Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices. Front Mol Neurosci 9:112 |
| Blaise, J Harry; Ruskin, David N; Koranda, Jessica L et al. (2015) Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats. Physiol Rep 3: |
