Role of neurogenic inflammation in intervertebral disc degeneration

Figure 4 Schematic of the major relationship between disc degeneration and neurogenic inflammation. Intervertebral disc injury or degeneration produces a large number of inflammatory mediators, including histamine, 5-HT, bradykinin, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nerve growth factor (NGF), H⁺, and prostaglandins. Each of these mediators sensitizes (lowers threshold) or stimulates the terminals of nociceptors by interacting with cell surface receptors expressed by the neurons innervating disc. Activation of nociceptors not only triggers an orthodromic action potential that transmits afferent information to the dorsal horn of the spinal cord but also invades local collaterals and terminals (antidromic activity) unaffected by the original insult, thus initiating the process of neurogenic inflammation. This is an efferent function of nociceptors in which neuropeptides, particularly substance P (SP) and calcitonin gene-related peptides (CGRP), are released from the peripheral terminals to induce vasodilation and plasma extravasation as well as the activation of non-neuronal cells, including disc cells and immune cells. These cells in turn release inflammatory mediators that aggravate the inflammatory response of the disc. TrkA: Tyrosine receptor kinase A.