FIGURE 1.

Signaling pathways of interest in the peripheral and central nociceptive pathway. Tissues innervated by the DRGs release proinflammatory mediators and neurotrophic factors, which act on their receptors on nerve endings and stimulate the NFκB response in DRGs. Damage to axons through compression or injury in age‐related degenerative diseases including intervertebral disc degeneration stimulates the expression of nerve injury markers and cell stress, such as, ATF3 and NPY. In response to damage or inflammation DRGs can dynamically regulate expression of cold and heat sensing ion channels, TRPA1 and TRPV1, and nociceptive neuropeptides, CALCA and TAC1. Nociceptive neuropeptides are released into the dorsal horn in the spinal cord where they act on their receptors RAMP1 and TACR1 to regulate expression in spinal nociceptive neurons