Nevertheless, in addition to Hes1, the potential contribution of other Hes families to pain-associated plasticity in the spinal neuraxis needs further studies to be elucidated because a genome-wide mapping analysis of brain tissue dissected from post-mortem Huntington’s disease patients revealed that the hyper-methylation of Hes4 promoter sequences was strikingly correlated with the measure of striatal degeneration and age-of-onset [26]. This evidence concerns the gene HES4 and Huntington disease.