Inflammatory mediators in intervertebral disk degeneration and discogenic pain

Abstract

Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α are expressed at higher levels in "diseased" intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain.

Keywords: cytokines; degenerative disk disease; discogenic pain; inflammatory mediators; innervation; intervertebral disk degeneration.

Fig. 1

Schematic representation of innervations and vascularization pattern in healthy and degenerate intervertebral disk. (A) Nerve fibers and blood vessels penetrate only the outer third of the AF in healthy disks with a high proteoglycan content. (B) Low oxygen levels, low glucose concentrations, end plate calcification, and adverse load contribute to an increased production of proteases, cytokines, and neurogenic and angiogenic factors resulting in matrix degradation and attraction of nerve fibers and blood vessels. (C) Nerve fibers and blood vessels penetrate deep into the degenerated disk as a result of the low proteoglycan content and the increased production of angiogenic and neurogenic mediators. Abbreviations: AF, annulus fibrosus; DRG, dorsal root ganglion; iAF, inner annulus fibrosus; NP, nucleus pulposus.