FIGURE 8.

Model of response to aging in the mouse somatosensory nervous system. Damage to nerves and demyelination due to age‐related degenerative diseases including intervertebral disc degeneration induces Atf3, possibly mediated by increased TRPA1 expression, which promotes expression of Npy and Bdnf. Nearby intact small diameter nerves respond to nerve damage by inducing Calca, resulting in increased CALCA expression which is transported to the SCDH which may induce further Calca expression in SCDH neurons, leading to central sensitization. Additionally, increased presence of TNFalpha in aging tissues or the circulatory system acts on its receptors, TNFR1/2, to induce NFκB pathway components, Rela and Nfkb1, which in turn increases expression of nociceptive sodium channels, NaV1.8 and NaV1.9. Higher sodium channel expression reduces thresholds and increases the stimulation of SCDH neurons