Nerve growth factor expression and innervation of the painful intervertebral disc.
Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.
Manchester University, UK. tony.freemont@man.ac.uk
A J
AJ
Freemont
A
A
Watkins
C
C
Le Maitre
P
P
Baird
M
M
Jeziorska
M T N
MT
Knight
E R S
ER
Ross
J P
JP
O'Brien
J A
JA
Hoyland
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D019902:Chondrocytes / Q000737:chemistry; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007403:Intervertebral Disc / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D017116:Low Back Pain / Q000378:metabolism*; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D009416:Nerve Regeneration; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D020917:Receptor, trkA / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis; D013869:Thiolester Hydrolases / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors; D043222:Ubiquitin Thiolesterase
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019922:GAP-43 Protein; C504649:PSIP1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D009418:S100 Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase