M1627K Mutation in Nav1.7 Causes Hyperexcitability in Pain Disorder
Author Information
Author(s): Dib-Hajj Sulayman D, Estacion Mark, Jarecki Brian W, Tyrrell Lynda, Fischer Tanya Z, Lawden Mark, Cummins Theodore R, Waxman Stephen G
Primary Institution: Yale University School of Medicine
Hypothesis
Does the M1627K mutation in Nav1.7 affect the excitability of dorsal root ganglion neurons?
Conclusion
The M1627K mutation in Nav1.7 leads to hyperexcitability of dorsal root ganglion neurons, contributing to pain in patients with paroxysmal extreme pain disorder.
Supporting Evidence
- The M1627K mutation was identified in a family with a history of paroxysmal extreme pain disorder.
- Patients with the mutation showed a significant reduction in the threshold for action potentials.
- Current-clamp recordings indicated that DRG neurons expressing M1627K fired more action potentials in response to stimuli.
Takeaway
A change in a gene called Nav1.7 makes nerve cells too excited, causing a lot of pain for some people.
Methodology
The study involved genetic sequencing, voltage-clamp electrophysiology, and current-clamp recordings from dorsal root ganglion neurons.
Limitations
The study did not examine the sensitivity of M1627K channels to carbamazepine.
Participant Demographics
The proband is a 36-year-old Caucasian female with a family history of paroxysmal extreme pain disorder.
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.005
Digital Object Identifier (DOI)
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