It has previously been suggested that more severe neuropathy appears to be associated with painful DPN (22, 29, 30, 48); thus, individuals with painful DPN may undergo a more advanced hypoxia-induced increase in skin blood vessels, which then expose local small nociceptive fibers to a relative excess of algogens such as nerve growth factor (24, 49, 50). This evidence concerns the gene NGF and neuropathy.