Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain?

Abstract

The normal intervertebral disc (IVD) is a poorly innervated organ supplied only by sensory (mainly nociceptive) and postganglionic sympathetic (vasomotor efferents) nerve fibers. Interestingly, upon degeneration, the IVD becomes densely innervated even in regions that in normal conditions lack innervation. This increased innervation has been associated with pain of IVD origin. The mechanisms responsible for nerve growth and hyperinnervation of pathological IVDs have not been fully elucidated. Among the molecules that are presumably involved in this process are some members of the family of neurotrophins (NTs), which are known to have both neurotrophic and neurotropic properties and regulate the density and distribution of nerve fibers in peripheral tissues. NTs and their receptors are expressed in healthy IVDs but much higher levels have been observed in pathological IVDs, thus suggesting a correlation between levels of expression of NTs and density of innervation in IVDs. In addition, NTs also play a role in inflammatory responses and pain transmission by increasing the expression of pain-related peptides and modulating synapses of nociceptive neurons at the spinal cord. This article reviews current knowledge about the innervation of IVDs, NTs and NT receptors, expression of NTs and their receptors in IVDs as well as in the sensory neurons innervating the IVDs, the proinflammatory role of NTs, NTs as nociception regulators, and the potential network of discogenic pain involving NTs.

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

“…By maintaining CSPG presence in the matrix, this has the potential to prevent nerve growth into the nucleus pulposus. Innervation of the nucleus pulposus has been demonstrated in patients with low back pain [13,14]. The ability of these solubilized dNP matrices to prevent nerve growth in vitro and in vivo is currently being explored.…”

“…The loss of CSPGs may additionally enable innervation of the disc and subsequent pain [11,12]. Discogenic pain is one source of low back pain that is thought to arise from increased nociceptive fiber innervation in the IVD [13,14].…”

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

“…Degenerated discs with structural abnormalities have been found to be more strongly correlated with discogenic pain than the normal changes with age [17]. Severely degenerated discs, including collapsed, prolapsed discs and discs showing leaking radial tears, exhibited a higher penetration of nociceptive nerve fibers toward the nucleus center [17,70,71]; this phenomenon has been associated with increased back pain [22]. Endplate lesions and irregular endplate loading were also found to be correlated with back pain history [74].…”

Discogenic pain: Who cares?

“…However, the available data has been obtained from experimentation in rats [5]. The normal IVD is poorly innervated, supplied only by sensory and sympathetic perivascular nerve fibers.…”

“…The IVD is then formed and consists of three different structures: a gelatinous core called nucleus pulposus (NP), an outer ring of fibrous tissue called annulus fibrosus (AF) and two vertebral endplates of hyaline cartilage that cover the upper and lower surface of both NP and AF [5]. The IVD along with the facet joints provide support and stability by limiting the movement of the spine in all directions [8,9].…”