Immunohistochemical and histological study of human uncovertebral joints
From: Spine (Phila Pa 1976). 2009 May 20;34(12):1257-63
There is controversy with regard to the anatomic and histological makeup of the uncovertebral interface with some authors considering it a joint and others disc tissue. No research has investigated the presence of pain generating neurotransmitters within the uncovertebral cartilaginous and capsular tissue.
The objective of this study was to investigate the anatomy and innervation of the uncovertebral joint to determine if it is synovial in nature and capable of generating pain.
Tissue from uncovertebral capsule and cartilage was harvested for each uncovertebral surface starting at the C2-C3 to the C6-C7 cervical segment. The tissue was placed in 4% paraformaldehyde fixative, then dehydrated and embedded in paraffin. Ten micron sections were cut through the tissue blocks and mounted on slides. The tissue was rehydrated and either stained with hematoxylin and eosin (H and E) or immunostained with antisera against protein gene product 9.5 (PGP 9.5), substance P (SP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP).
The sample consisted of 2 unembalmed fresh male human cadavers of a mean age of 83 years. Chondrocytes and synoviocytes were identified at the capsular tissue of each uncovertebral interface from C2-C3-C6-C7. Immunoreactivity for PGP 9.5, SP, CGRP, and NPY was observed at all uncovertebral interface levels in capsular tissue.
The presence of both synoviocytes and chondrocytes has been recorded in the present study, suggesting that the uncovertebral interface is synovial in nature. Immunoreactivity to PGP 9.5, SP, CGRP, and NPY indicates the presence of nerve fibers from both the somatic and autonomic nervous systems. These findings suggest that the uncovertebral joints are potential pain generators in the cervical spine.
Numerous investigators have referred to the uncovertebral region, but fewer have described the joint from a histologic standpoint. The uncovertebral interfaces were first described by Rathke and Von Luschka over a hundred years ago. In 1834, Rathke described the uncinate processes as prominences found in the posterior craniolateral edges of the vertebral body that bordered fissures extending medially into the anulus fibrosus. Von Luschka named these prominences as the eminentia costaria because of their resemblance to the head of a rudimentary rib.
The notion representing the uncovertebral interface as a joint is uncontestable, but the presence of a synovial cavity within the joint is controversial. Von Lushka suggested that the uncinate processes were associated with a joint cavity found medially projecting into the anulus and lined with a synovial membrane that exhibited papillary elements responsible for secreting synovial fluid. Other investigators have attempted to describe the uncovertebral joint as a synovial compartment, but lacked technical accuracy. More information regarding the precise structure of the joint is necessary for complete understanding of its function.
The clinical relevance of the uncovertebral joint has been investigated. While the uncovertebral joint has been primarily evaluated in context with degeneration leading to intervertebral foraminal stenosis, nerve root compression syndrome, and the potential need for decompressive surgery, the joint’s role as a pain generator in cervicalgia has not been fully examined. Structural and functional changes in the uncovertebral joint have been cited as potential triggers for pain generation in cervicalgia. However, those changes do not appear to be strongly related to the levels of pain and disability in patients with neck pain. Thus, to date no research has examined the anatomy of the uncovertebral joint to confirm if it is synovial in nature and to determine its capacity for generating pain.
To implicate structures as pain generators in the cervical spine, nerve supplies must be evaluated. Bogduk et al described the nerve distribution to the cervical intervertebral disc, while Yamada et al discussed specific sympathetic innervation. Additionally, investigators have described the immunoreactivity of certain substances such as nitric oxide synthase and substance P (SP) in the cervical disc. Further studies have established the cervical zygapophyseal joints as pain generators. Moreover, Kallakuri et al observed immunoreactivity to SP and calcitonin gene-related peptide (CGRP) in human cervical zygapophyseal joint capsules. However, similar studies have not been conducted with respect to the uncovertebral joint.
The presence of both synoviocytes and chondrocytes has been recorded at the uncovertebral joint, suggesting that the structure is synovial in nature. A nerve supply was documented in the region and immunoreactivity to PGP 9.5, SP, NPY, and CGRP was identified, which are indicative of the presence of nerve fibers from the somatic and autonomic nervous systems. These findings suggest the uncovertebral joints are potential pain generators in the cervical spine. Future research should focus on determining whether the chondrocytic tissue is hyaline or fibrocartilaginous in nature. Additionally, the originating spinal levels and peripheral nerve sources for the nerve supply should be traced. Furthermore, the influence of the sympathetic nervous system on cervical pain should be evaluated. Finally, the influence of age on the findings from the present study should be examined, considering the documented changes that occur in the cervical disc segments.
