title: Nerves are more abundant than blood vessels in the degenerate human intervertebral disc.
abstract: BACKGROUND
  Chronic low back pain (LBP) is the most common cause of disability worldwide. New ideas surrounding LBP are emerging that are based on interactions between mechanical, biological and chemical influences on the human IVD. The degenerate IVD is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. However, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. We investigated the presence of nerves and blood vessels in the nucleus pulposus (NP) of the IVD in a large population of human discs.
  
  
  METHODS
  Immunohistochemistry was performed with 61 human IVD samples, to identify and localise nerves (neurofilament 200 [NF200]/protein gene product 9.5) and blood vessels (CD31) within different regions of the IVD.
  
  
  RESULTS
  Immunopositivity for NF200 was identified within all regions of the IVD within post-mortem tissues. Nerves were seen to protrude across lamellar ridges and through matrix towards NP cells. Nerves were identified deep within the NP and were in many cases, but not always, seen in close proximity to fissures or in areas where decreased matrix was seen. Fifteen percent of samples were degenerate and negative for nerves and blood vessels, whilst 16 % of all samples were degenerate with nerves and blood vessels. We identified 52% of samples that were degenerate with nerves but no blood vessels. Interestingly, only 4% of all samples were degenerate with no nerves but positive for blood vessels. Of the 85 samples investigated, only 6 % of samples were non-degenerate without nerves and blood vessels and 7% had nerves but no blood vessels.
  
  
  CONCLUSIONS
  This study addresses the controversial topic of nerve and blood vessel ingrowth into the IVD in a large number of human samples. Our findings demonstrate that nerves are present within a large proportion of NP samples from degenerate IVDs. This study shows a possible link between nerve ingrowth and degeneration of the IVD and suggests that nerves can migrate in the absence of blood vessels.
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK. abbie.l.binch@student.shu.ac.uk.
authors.forename: Abbie L A
authors.initials: AL
authors.lastname: Binch
authors.affiliation: Department of Spinal Surgery, Sheffield Teaching Hospitals, Sheffield, UK. ashley.cole@sth.nhs.uk.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Cole
authors.affiliation: Department of Spinal Surgery, Sheffield Teaching Hospitals, Sheffield, UK. lee.breakwell@sth.nhs.uk.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Breakwell
authors.affiliation: Department of Spinal Surgery, Sheffield Teaching Hospitals, Sheffield, UK. antony.michael@sth.nhs.uk.
authors.forename: Antony L R
authors.initials: AL
authors.lastname: Michael
authors.affiliation: Department of Spinal Surgery, Sheffield Teaching Hospitals, Sheffield, UK. neil.chiverton@sth.nhs.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Chiverton
authors.affiliation: Department of Orthopaedics, University Medical Centre Utrecht, Utrecht, The Netherlands. l.b.creemers@umcutrecht.nl.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK. a.k.cross@shu.ac.uk.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Cross
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK. c.lemaitre@shu.ac.uk.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Le Maitre
mesh_terms: D006801:Humans; D007403:Intervertebral Disc / Q000098:blood supply* / Q000737:chemistry / Q000294:innervation* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology; D017116:Low Back Pain / Q000473:pathology; D016900:Neurofilament Proteins / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D016900:Neurofilament Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C051774:neurofilament protein H