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Only the subgroup of<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>\u2010patients with mutations in sodium channel subunits Na<jats:sub>V<\/jats:sub>1.7, 1.8 or 1.9 (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) had increased lidocaine sensitivity for<jats:italic>supra<\/jats:italic>\u2010threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na<jats:sub>V<\/jats:sub>1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Heat pain thresholds are not sensitized in<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>patients, even in those with gain\u2010of\u2010function mutations in Na<jats:sub>V<\/jats:sub>1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the<jats:italic>supra<\/jats:italic>\u2010threshold range suggesting that sensitized<jats:italic>supra<\/jats:italic>\u2010threshold encoding is important for the clinical pain phenotype in<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>in addition to lower activation threshold. Intracutaneous lidocaine dose\u2010dependently blocked nociceptive sensations, but we did not identify<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Acute pain thresholds and<jats:italic>supra<\/jats:italic>\u2010threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>patients with the Na<jats:sub>V<\/jats:sub>1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>patients with mutations in Na<jats:sub>V<\/jats:sub>1.7, 1.8 or 1.9<jats:italic>supra<\/jats:italic>\u2010threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1030","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T10:07:35Z","timestamp":1492510055000},"page":"1316-1325","source":"Crossref","is-referenced-by-count":9,"title":["Pain thresholds,<i>supra<\/i>\u2010threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in Na<sub>V<\/sub>1.7"],"prefix":"10.1002","volume":"21","author":[{"given":"T.","family":"Hel\u00e5s","sequence":"first","affiliation":[{"name":"Section\u00a0of Clinical Neurophysiology, Department of Neurology Oslo University Hospital \u2013 Rikshospitalet 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