In accordance with the reported association between increased TLR expression and increased degree of disc degeneration and pain [261], double staining for p16INK4a and TLR-2 revealed their co-localization in human TLR-2/6 activation-induced senescent IVD cells from non-degenerate and degenerated tissues [73]. Here, CDKN2A is linked to intervertebral disk degenerative disorder.