CALCRL and Dowling-Degos disease 1: With respect to anatomically generated pain, it has been extensively reported that painful intervertebral discs (IVD) strongly express proteins (neurotrophins) that are associated with painful DDD, including nerve growth factor and its receptor (NGFr/TrkA), brain derived neurotrophic factor (BDNF), the BDNF receptor (TrkB), the neuropeptides calcitonin gene related peptide (CGRP) and its receptor (CALCRL), and Substance p (Sub p) [9,10,11].