title: Nerve ingrowth into diseased intervertebral disc in chronic back pain.
abstract: 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 [GAP43]).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, University of Manchester, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Freemont
authors.forename: T E
authors.initials: TE
authors.lastname: Peacock
authors.forename: P
authors.initials: P
authors.lastname: Goupille
authors.forename: J A
authors.initials: JA
authors.lastname: Hoyland
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: M I
authors.initials: MI
authors.lastname: Jayson
mesh_terms: D000328:Adult; D001416:Back Pain / Q000209:etiology* / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein; D006801:Humans; D007403:Intervertebral Disc / Q000294:innervation* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis; D012016:Reference Values; D013373:Substance P / Q000032:analysis
chemical_list: D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D013373:Substance P