Mf. Brown et al., SENSORY AND SYMPATHETIC INNERVATION OF THE VERTEBRAL END-PLATE IN PATIENTS WITH DEGENERATIVE DISC DISEASE, Journal of bone and joint surgery. British volume, 79B(1), 1997, pp. 147-153
We obtained intervertebral discs with cartilage endplates and underlyi
ng cancellous bone at operation from patients with degenerative disc d
isease and then used immunohistochemical techniques to localise the ne
rves and nerve endings in the specimens. We used antibodies for the ub
iquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity
to neuropeptide Y was used to identify autonomic nerves and calcitoni
n gene-related peptide (CGRP) and substance P to identify sensory nerv
es. Blood vessels were identified by immunoreactivity with platelet-en
dothelial cell-adhesion molecule (CD31; PECAM). In a control group wit
h no known history of chronic back pain, nerve fibres immunoreactive t
o PGP 9.5 and neuropeptide Y were most closely related to blood vessel
s, 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 end
plate region and underlying vertebral bodies. Many of these nerves wer
e immunoreactive to substance P or CGRP, and in addition, substance P-
and CGRP-immunoreactive nociceptors were seen unrelated to blood vess
els. 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 breakdo
wn is responsible for the proliferation of vascularity and CGRP-contai
ning sensory nerves found in the endplate region and vertebral body ad
jacent to degenerate discs. The neuropeptides substance P and CGRP hav
e potent vasodilatory as well as pain-transmitting effects. The increa
se in sensory nerve endings suggests increase in blood how perhaps as
an attempt to augment the nutrition of the degenerate disc. The increa
se in the density of sensory nerves, and the presence of endplate cart
ilage defects, strongly suggest that the endplates and vertebral bodie
s are sources of pain; this may explain the severe pain on movement ex
perienced by some patients with degenerative disc disease.