Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc herniation and spondylosis.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)–3, tumor necrosis factor (TNF)–α, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFα and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFα, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFα expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.</jats:p></jats:sec>

Inflammation in intervertebral disc degeneration and regeneration

“…Immunoreactivity for some cytokines (IL-4, IL-6, IL-12, IFN-g, TNF-a) seemed modest but evident in herniated and degenerated discs, with substantial macrophage infiltration [116,122]. Also, pathologic discs highly expressed IL-17, suggesting the involvement of Th17 lymphocytes in disc herniation [123].…”

Cervical spondylotic amyotrophy

“…Cervical spondylosis often manifests with spastic tetraparesis with varying degrees of sensory dysfunction [6,10,11,14,26,45]. Crandall et al [10] indicated that somewhat less than 7% of patients with cervical spondylotic myelopathy present with minimal sensation loss, and classified this subtype of the disorder as cervical spondylotic amyotrophy.…”

Inhibition of miR‑27a suppresses the inflammatory response via the p38/MAPK pathway in intervertebral disc cells

“…Endogenous factors, including crystal deposits in the annulus of human intervertebral discs and ECM breakdown products, can trigger the IVD inflammatory response (30,31). Various proinflammatory cytokines, including IL-1β, IL-6, IL-12 and TNF-α, were significantly increased due to immunoreactivity in herniated and generative IVD tissues (32,33). To investigate the role of miR-27a in IDD, a stable miR-27a-knockdown NP cell line was generated by transfection with an miR-27a inhibitor, and an IDD cell model was established by LPS stimulation of cells.…”