A SCN10A SNP biases human pain sensitivity

Area of Science:

• Neuroscience
• Genetics
• Pain Research

Background:

• Nav1.8 sodium channels, encoded by SCN10A, are crucial for human pain perception.
• While rare SCN10A variants cause neuropathies, the impact of common variants on pain remains unclear.

Purpose of the Study:

• To investigate if common SCN10A variants affect human pain sensitivity.
• To explore the channel and neuronal level mechanisms underlying these effects.

Main Methods:

• Employed a candidate single nucleotide polymorphism (SNP) association study.
• Utilized experimental pain testing in human cohorts (discovery and replication).
• Conducted functional assessments of SCN10A variants at the channel and neuronal levels.

Main Results:

• Identified an association between SCN10A SNP rs6795970 (Ala1073Val) and higher mechanical pain thresholds.
• Confirmed this association in independent cohorts.
• Functional studies revealed that rs6795970 alters Nav1.8 channel kinetics, reducing dorsal root ganglion neuron firing and lowering pain sensitivity.

Conclusions:

• The SCN10A polymorphism rs6795970 significantly influences human pain sensitivity.
• This SNP affects pain perception through mechanisms at both the genetic association and channel function levels.