Innervation of the Human Intervertebral Disc: A Scoping Review

Abstract

Objective: Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, and consequences. Notably, the underlying pathology remains unknown in a significant number of cases. Changes to the intervertebral disc (IVD) have been associated with back pain, leading many to postulate that the IVD may be a direct source of pain, typically referred to as discogenic back pain. Yet, despite decades of research into the neuroanatomy of the IVD, there is a lack of consensus in the literature as to the distribution and function of neural elements within the tissue. The current scoping review provides a comprehensive systematic overview of studies that document the topography, morphology, and immunoreactivity of neural elements within the IVD in humans. <uMel>thod: Articles were retrieved from six separate databases in a three-step systematic search, and independently evaluated by two reviewers. <Resul>ults: Three categories of neural elements were described within the IVD: perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors. Nerves were consistently localized within the outer layers of the annulus fibrosus. Neural ingrowth into the inner annulus fibrosus and nucleus pulposus was found to occur only in degenerative states and disease states. Conclusion: While the pattern of innervation within the IVD is clear, the specific topographic arrangement and function of neural elements in the context of back pain remains unclear.

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

“…The normal structure of IVD is avascular that is poorly innervated, with the most nerve fibers existing in the outer 1/3 of AF [ 12 ]. In the past few decades, the role and changes of nerve systems during the progression of IVDD have attracted growing attention among researches [ 13 ]. A recent scope review suggested that during the process of IVDD, the neurovascularization within the disc, especially the NP tissue, is gradually evident, which is frequently located at regions of tissue granulation, tears, and lesions [ 14 ].…”

The involvement of immune system in intervertebral disc herniation and degeneration

“…Inherently, the native attempt to address IVD injury or tears is through the process of vascularization and innervation into the disc. In healthy discs, nerve fibers, which include perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors, appeared only on the surface of the AF 62 . Healthy discs have no substance P‐expressing nerve fibers in the inner AF and NP, which were detected only in degenerated discs 62,63 .…”

“…In healthy discs, nerve fibers, which include perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors, appeared only on the surface of the AF 62 . Healthy discs have no substance P‐expressing nerve fibers in the inner AF and NP, which were detected only in degenerated discs 62,63 . The invasion of nerves may be the consequence of increased nerve growth factor expression during degeneration 64 .…”

“… 62 Healthy discs have no substance P‐expressing nerve fibers in the inner AF and NP, which were detected only in degenerated discs. 62 , 63 The invasion of nerves may be the consequence of increased nerve growth factor expression during degeneration. 64 Since these nerve fibers are unmyelinated and use substance P as the neurotransmitter, their appearance is closely associated with pain.…”

Stem Cell Therapy and Exercise for Treatment of Intervertebral Disc Degeneration

“…Because of the avascular feature of the ventral NP, the concentration of oxygen, some metabolites, and blood is transported by vascular slumps from the AF to the NP, though the lactic acid concentration and hydrostatic pressure are relatively high [ 13 ]. Nerves commonly travel along the blood vessels, while some of them also develop without blood vessels [ 14 , 15 ].…”