{"doi":"10.1016/j.ynpai.2023.100138","title":"ATP-gated potassium channels contribute to ketogenic diet-mediated analgesia in mice","abstract":"Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (KATP) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a KATP channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of KATP channels with the KATP channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK+ cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of KATP channels to provide ketogenic diet-related analgesia. This study also identifies KATP channels as a new target to mimic the antinociceptive effects of a ketogenic diet.","journal":"Neurobiology of Pain","year":2023,"id":371352,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":624093,"name":"Sarah Thomas","orcid":"0000-0003-0226-7270","position":1,"is_corresponding":false},{"id":847902,"name":"Paige Lynch","orcid":"0009-0008-7738-3480","position":2,"is_corresponding":false},{"id":891084,"name":"Jarrid Jack","orcid":null,"position":3,"is_corresponding":false},{"id":722532,"name":"Janelle M. Ryals","orcid":null,"position":4,"is_corresponding":false},{"id":261889,"name":"Patrycja Puchalska","orcid":"0000-0002-1875-1203","position":5,"is_corresponding":false},{"id":261898,"name":"Peter A. Crawford","orcid":"0000-0001-8597-4426","position":6,"is_corresponding":false},{"id":1130968,"name":"Douglas E. Wright","orcid":"0000-0002-7578-8694","position":7,"is_corresponding":false},{"id":721854,"name":"Jonathan Enders","orcid":"0000-0001-9943-4498","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:15:45.330525Z","pmid":"38099277","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}