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The PDC is an important mitochondrial gatekeeping enzyme that controls cellular metabolism. The role of PDKs in diverse neurological disorders, including neurometabolic aberrations and neurodegeneration, has been described. Implications for a role of PDKs in inflammation and neurometabolic coupling led us to investigate the effect of genetic ablation of PDK2\/4 on nociception in a mouse model of acute inflammatory pain. Deficiency in <jats:italic>Pdk2<\/jats:italic> and\/or <jats:italic>Pdk4<\/jats:italic> in mice led to attenuation of formalin\u2010induced nociceptive behaviors (flinching, licking, biting, or lifting of the injected paw). Likewise, the pharmacological inhibition of PDKs substantially diminished the nociceptive responses in the second phase of the formalin test. Furthermore, formalin\u2010provoked paw edema formation and mechanical and thermal hypersensitivities were significantly reduced in <jats:italic>Pdk2\/4<\/jats:italic>\u2010deficient mice. Formalin\u2010driven neutrophil recruitment at the site of inflammation, spinal glial activation, and neuronal sensitization were substantially lessened in the second or late phase of the formalin test in <jats:italic>Pdk2\/4\u2010<\/jats:italic>deficient animals. Overall, our results suggest that PDK2\/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23727","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T04:50:44Z","timestamp":1456894244000},"page":"837-849","source":"Crossref","is-referenced-by-count":17,"title":["Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain"],"prefix":"10.1002","volume":"94","author":[{"given":"Mithilesh Kumar","family":"Jha","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Brain Science and Engineering Institute, BK21 Plus KNU Biomedical Convergence Program Kyungpook National University School of Medicine Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md 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