For example, several heritable connective tissue disorders caused by defects in collagen-encoding or collagen-regulating genes display a pain phenotype, which is phenocopied in their corresponding murine models (e.g., Col1a1Jrt/+ and Col5a1+/− mice), suggesting that healthy core matrisome and matrisome-associated signaling is crucial for normal neuronal function and pain perception (Abdelaziz et al., 2015; Syx et al., 2020). This evidence concerns the gene COL5A1 and connective tissue disorder.