SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology

Ryan Castoro, Megan Simmons, Vignesh Ravi, Derek Huang, Christopher Lee, John Sergent, Lan Zhou, Jun Li

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objective The SCN11A gene encodes the NaV1.9 sodium channel found exclusively in peripheral nociceptive neurons. Methods All enrolled participants were evaluated clinically by electrophysiologic studies, DNA sequencing, and punch skin biopsies. Results All affected family members are afflicted by episodes of pain. Pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyalgia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology. Conclusions Unlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy, and neuropathic pain, the Arg225Cys SCN11A in the present study causes predominantly nociceptive pain with minimal features of neuropathic pain and undetectable pathophysiologic changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand the clinical spectrum beyond painful small fiber sensory neuropathy.

Original languageEnglish
Article numbere255
JournalNeurology: Genetics
Issue number4
StatePublished - 1 Aug 2018
Externally publishedYes


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