Determine whether single nucleotide polymorphisms (SNPs) of the calcitonin gene-related polypeptide (CGRP)-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) are related to headache burden during the first week after concussion.

Post-traumatic headache is a commonly reported symptom after concussion.  SNPs related to CGRP are involved in the pathogenesis of migraine headaches and contribute to pain transmission and neurogenic inflammation. It is unclear in concussed persons if the headache burden is associated with genetic variations related to CGRP.  

A prospective study was performed in 20 concussed athletes (gender: 12 female, 8 male; age: 19±1 years; height: 1.75±0.10 meters; weight: 70±10 kilograms).  Participants completed the symptom evaluation checklist from the SCAT3 within 48 hours of injury (V1), and 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0-6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were summed.  The area under-the-curve (AUC) was computed for the total (V1+V2+V3), early (V1 to V2) and late (V2 to V3) burden of headache-related symptoms.  A saliva sample was obtained, and a commercial laboratory identified the genotype for CALCA (rs3781719) and RAMP1 (rs10185142) using PMR-array.

Genetic variability for CALCA was low within our sample and not used.  RAMP1 genotypes (CC, TC, TT) were dichotomized (T+, T-) to facilitate analyses. The total headache burden AUC was significantly greater (p<0.05, power: 0.580) in the T+ (n=13) compared to the T- (n=7) group [43.2(±19.5) vs. 24.0(±14.5)].  The early burden AUC was significantly greater (p=0.014, power: 0.726) in the T+ compared to the T- group [28.6(±11.4) vs. 15.4(±7.9)], but the late burden was not [14.6(±9.9) vs. 8.6(±7.9)].  Diagnosed concussion history did not contribute to the analyses.

The current analysis provides a proof-of-concept to suggest that the T allele for RAMP1 (rs10185142) was associated with a greater headache burden after concussion injury.