<div></div><div>Classical trigeminal neuralgia (cTN) is a neuropathic pain disorder
marked by evoked and spontaneous attacks in the distribution of the
trigeminal nerve, and the disorder is further associated with periods of
complete remission and subsequent recurrence in most patients. The pain
of cTN is considered to be amongst the most debilitating types of pain.
Neurovascular compression (NVC) of the trigeminal nerve has been
accepted as the cause of cTN in a majority of patients by the
International Headache Society (IHS). The condition is usually sporadic,
although a recent publication suggests that familial occurrence may be
more common than previously considered (2). A mutation in <i>SCN8A</i> ,
a sodium channel gene that codes for the Na<sub>v</sub>1.6 protein,
was reported in a 64-year-old white female that presented with classical
trigeminal neuralgia. The Met136Val change produced a significant
increase in peak transient and resurgent currents of
Na<sub>v</sub>1.6, reduced the threshold for action potential in
trigeminal ganglia neurons, and enhanced the neuronal evoked response
and the fraction of neurons that fire at a higher rate than those
expressing wild type channels (3). Mutations in <i>SCN8A</i> are known
to cause <i>SCN8A</i> -related epilepsy with encephalopathy, a rare
condition that has been reported in 50 individuals worldwide, which is
characterized by developmental delay, seizure onset in the first 18
months of life (mean 4 months), and intractable epilepsy characterized
by multiple seizure types (4). Since it was not clear from the original
report how frequent the Met136Val variant in <i>SCN8A</i> is among
individuals with trigeminal neuralgia, we tested the hypothesis that the
mutation <i>SCN8A</i> Met136Val is an infrequent finding in individuals
with trigeminal neuralgia.</div><div>One hundred and twenty-three individuals diagnosed with trigeminal
neuralgia were recruited since January 2016 to be part of our Orofacial
Pain Registry and Sample Repository project (IRB approval # 15110027).
They were 81 females, 110 Whites, and all adults at least 45 years of
age. These individuals provided written informed consent and a
biological sample (unstimulated saliva) and are from the most part from
the western Pennsylvania region. All cases were diagnosed by the same
professional (R.F.S.) using the same criteria. DNA was extracted from
saliva according to a published protocol (5) and samples were sequenced
in both directions to determine the presence of the <i>SCN8A</i>Met136Val mutation in the exon 4 of the gene. We designed a set of
primers (5’ TGT GCT TCA TCT CCT TTC AGG 3’ forward and 5’ CCA CAT TCT
TCG ACC AGT CA 3’ reverse) using the Primer3 online software
(http://primer3.ut.ee/). Polymerase chain reactions (PCR)
conditions were 30 cycles at 95°C for 30 seconds, 55°C for 30 seconds,
and 72°C for 1 minute, followed by a 7 minute-hold at 72°C. Sequences
were analyzed using the DNA Analysis Software Sequencher 5.0 (Sequencher
5.0: Gene Codes, Ann Harbor, Michigan, USA; http://genecodes.com/).</div><div>We did not find any case with the <i>SCN8A</i> Met136Val, which suggests
that the frequency of this mutation explains less than 1% of cases of
trigeminal neuralgia in populations.</div><div>These findings should help guide future study designs that aim to
identify associations between sodium channel genes and trigeminal
neuralgia. Analyses of common variants of Na<sub>v</sub>1.7
(<i>SCN9A</i> rs6746030) and nerve growth factor receptor (<i>SCN9A</i>rs6746030) of 48 individuals did not show overrepresentation of alleles
in cases with trigeminal neuralgia (6) and it is likely that several
hundred to thousands of individuals are necessary for enough statistical
power to detect associations.</div><div>Acknowledgements</div><div>The authors have no conflict of interest to declare. We thank the
enthusiastic participation of all subjects.</div><div>References</div><div>1. Cruccu, G., Bonamico, L.H., &amp; Zakrzewska, J.M. (2010). Cranial
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