Early ReportNerve ingrowth into diseased intervertebral disc in chronic back pain
Introduction
Chronic low back pain is one of the leading causes of morbidity and loss of work. The pathogenesis of this disorder is poorly understood, mainly because it is difficult to study objectively. Chronic low back pain is generally thought to be caused by nerve-root compression. However, magnetic resonance imaging often fails to show compression of neural structures, even in the presence of sciatica. Furthermore, back pain and sciatica can be recapitulated by manoeuvres that do not affect the nerve root, such as intradiscal saline injection, discography, and compression of the longitudinal spinal ligaments1 These observations have led to re-examination of pain pathways and the distribution of nociceptive nerve endings in healthy and diseased spines. Several studies have implicated the intervertebral disc in low back pain.2, 3, 4, 5, 6 A better understanding of the innervation of the intervertebral discs would elucidate the poorly understood mechanisms of this pain. Modern immunohistochemical techniques have facilitated the demonstration that in healthy adult animals and human beings nerves extend no further into the intervertebral disc than the outer third of the annulus fibrosus,4, 7, 8, 9, 10, 11, 12 and that these nerves may contain putative nociceptive neurotransmitters such as substance P, calcitonin-gene-related peptide, and vasoactive intestinal peptide.5, 13, 14 Two studies reported nerves in the annulus fibrosus and the nucleus pulposus of diseased intervertebral discs,1, 15 but there have been no systematic studies of the extent and nature of this innervation or its relation to clinical pain. We examined the role of nerve ingrowth into diseased intervertebral disc in chronic low back pain.
Section snippets
Methods
57 biopsy samples of the anterior parts of L3 to L5 intervertebral discs were obtained for histological testing from 40 patients during combined anterior and posterior fusion surgery for chronic (>12 months) back pain. Before biopsy, none of the patients had undergone procedures affecting the anterior aspect of the intervertebral disc, and they were taking only non-steroidal analgesics. To assess the anatomical pain level we reproduced the original site of pain by preoperative discography. The
Results
In the 34 control samples of intervertebral discs, the anterior ligament and the annulus fibrosus consisted of intact, well-oriented collagen fibres. Although rare, blood vessels were seen in the anterior longitudinal ligament and the outermost layers of the annulus fibrosus. Blood vessels penetrated into the middle third of the annulus fibrosus in only two control samples. The nucleus pulposus from controls consisted of well-ordered cartilage with few chondrocyte clusters (three or more
Discussion
Our findings show that there is an association between ingrowth of nerves expressing substance P and discal degeneration, and that the extent of neoneuralisation is greatest at intervertebral disc levels at which the patient experiences pain. Most of the small nerves identified by PGP9·5 and substance P immunohistochemistry accompany blood vessels. These nerves do not express GAP43, the protein associated with nerve growth, and all the morphological evidence suggests that they are associated
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