Sensory And Sympathetic Innervation Of The Vertebral Endplate In Patients With Degenerative Disc Disease

Abstract

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease.

UHMWPE Wear Debris and Tissue Reactions Are Reduced for Contemporary Designs of Lumbar Total Disc Replacements

“…The presence of these reactions in both cohorts is noteworthy because these reactions have been implicated in the development of pain. Specifically, increased vascularization (angiogenesis) and sensory nerve growth are closely linked processes [5,24]; and tissue necrosis or cell death results in the release of proinflammatory cytokines and other factors that initiate persistent pain by directly activating nociceptive sensory neurons [6,38]. Both reactions can lead to maladaptive plasticity and neural disease states, which raises the question whether these tissue responses contributed to neuropathic pain in both fixed-and mobile-bearing L-TDR patients.…”

Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators

“…Discs which cause low back pain have higher concentrations of sensory nerves than are seen in those which do not cause such pain. 14,15 The sensory nerves in the former are found in the endplates and in the nucleus pulposus and lose their normal relationship with blood vessels. The ingrowth of nerves into degenerate discs which cause low back pain may be mediated by chemotactic substances released by the degenerating disc.…”

“…It has been shown, however, that degenerate discs in these patients contain more nociceptive nerve endings in the endplates of the disc and in the nucleus pulposus than do degenerate discs which do not cause low back pain. 14, 15 We have therefore compared levels of production of the proinflammatory mediators tumour necrosis factor alpha (TNF␣), interleukin-1beta (IL-1␤), interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E 2 (PGE 2 ), in disc tissue from patients undergoing discectomy for sciatica with those from patients undergoing fusion for discogenic low back pain. …”

The vertebral endplate: disc degeneration, disc regeneration

“…Additional studies have identified nerve fibres and blood vessels in the endplates and subchondral bone in degenerate discs suggesting that tissue repair may be associated with back pain [11,17].…”