Neanderthal introgression in SCN9A impacts mechanical pain sensitivity

Area of Science:

• Genetics
• Neuroscience
• Human Evolution

Background:

• The Nav1.7 channel is crucial for pain signaling (nociception).
• Specific SCN9A gene variants (M932L, V991L, D1908G) linked to Neanderthal introgression affect pain.
• These variants are prevalent in Latin American populations but absent in Europeans.

Purpose of the Study:

• To investigate Neanderthal introgression within the SCN9A gene in Latin American populations.
• To experimentally assess the impact of these archaic variants on pain thresholds in healthy individuals.

Main Methods:

• Analysis of high-density genotype data from 7594 Latin Americans to identify Neanderthal introgression tracts in SCN9A.
• Experimental measurement of six pain thresholds in 1623 healthy Colombians.

Main Results:

• Identified Neanderthal introgression tracts in SCN9A on a Native American genomic background, averaging ~123 kb.
• Neanderthal ancestry in SCN9A was significantly associated with a lower mechanical pain threshold after mustard oil sensitization.
• Evidence suggests additive effects of Neanderthal variants across Nav1.7.

Conclusions:

• Confirms the association of Neanderthal Nav1.7 variants with clinical pain perception.
• Defines mechanical hyperalgesia as a sensory modality affected by archaic introgression in SCN9A.
• Findings support independent functional effects of Neanderthal variants on Nav1.7 channel activity.