Elsevier

The Lancet

Volume 350, Issue 9072, 19 July 1997, Pages 178-181
The Lancet

Early Report
Nerve ingrowth into diseased intervertebral disc in chronic back pain

https://doi.org/10.1016/S0140-6736(97)02135-1Get rights and content

Summary

Background

In the healthy back only the outer third of the annulus fibrosus of the intervertebral disc is innervated. Nerve ingrowth deeper into diseased intervertebral disc has been reported, but how common this feature is and whether it is associated with chronic pain are unknown. We examined nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.

Methods

We collected 46 samples of intervertebral discs from 38 patients during spinal fusion for chronic back pain. 30 samples were from pain levels clinically established by discography and 16 samples were from adjacent vertebral levels with no pain. We obtained 34 control samples of intervertebral disc from previously healthy individuals with normal histology within 8 h of recorded death. We used standard immunohistochemical techniques to test for a general nerve marker, a nociceptive neurotransmitter (substance P), and a protein expressed during axonogenesis (growth-associated protein 43·43 [GAP43]).

Findings

We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%) of the 80 samples of intervertebral discs. Nerves were restricted to the outer or middle third of the annulus fibrosus in the 34 control samples. Among the patients with chronic low back pain, nerves extended into the inner third of the annulus fibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) samples, respectively. Nerves usually accompanied blood vessels, but in 14 of the samples from back-pain patients, isolated nerve fibres were seen in the discal matrix. Both types of nerve fibres expressed substance P, but only non-vessel-associated fibres expressed GAP43. Deep nerve ingrowth into the inner third of the annulus fibrosus, the nucleus pulposus, or both was seen in four (25%) of 16 biopsy samples from non-pain levels and in 17 (57%) samples from pain levels. Of the 16 paired samples from both pain and non-pain levels, five pain-level samples and one non-pain-level sample showed deep nerve ingrowth.

Interpretation

Our finding of isolated nerve fibres that express substance P deep within diseased intervertebral discs and their association with pain suggests an important role for nerve growth into the intervertebral disc in the pathogenesis of chronic low 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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