title: Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.
abstract: Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-α, interleukin-1β, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo.
authors.affiliation: Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, Montreal, QC, Canada.
authors.forename: Emerson
authors.initials: E
authors.lastname: Krock
authors.forename: Derek H
authors.initials: DH
authors.lastname: Rosenzweig
authors.forename: Anne-Julie
authors.initials: AJ
authors.lastname: Chabot-Doré
authors.forename: Peter
authors.initials: P
authors.lastname: Jarzem
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weber
authors.forename: Jean A
authors.initials: JA
authors.lastname: Ouellet
authors.forename: Laura S
authors.initials: LS
authors.lastname: Stone
authors.forename: Lisbet
authors.initials: L
authors.lastname: Haglund
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000150:complications / Q000503:physiopathology*; D017116:Low Back Pain / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D059225:Nociception / Q000502:physiology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; discogenic pain; human; inflammatory cytokines; intervertebral disc degeneration; nerve growth factor