PMID- 24650225
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20211021
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 18
IP  - 6
DP  - 2014 Jun
TI  - Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP 
      through nociceptive factors.
PG  - 1213-25
LID - 10.1111/jcmm.12268 [doi]
AB  - 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-alpha, interleukin-1beta, 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.
CI  - (c) 2014 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Krock, Emerson
AU  - Krock E
AD  - Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill 
      University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, 
      Montreal, QC, Canada.
FAU - Rosenzweig, Derek H
AU  - Rosenzweig DH
FAU - Chabot-Dore, Anne-Julie
AU  - Chabot-Dore AJ
FAU - Jarzem, Peter
AU  - Jarzem P
FAU - Weber, Michael H
AU  - Weber MH
FAU - Ouellet, Jean A
AU  - Ouellet JA
FAU - Stone, Laura S
AU  - Stone LS
FAU - Haglund, Lisbet
AU  - Haglund L
LA  - eng
GR  - MOP-119564/Canadian Institutes of Health Research/Canada
GR  - MOP-86691/Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140320
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Calcitonin Gene-Related Peptide/genetics/*metabolism
MH  - Case-Control Studies
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Female
MH  - Humans
MH  - Interleukin-1beta/genetics/metabolism
MH  - Intervertebral Disc Degeneration/complications/*physiopathology
MH  - Low Back Pain/*etiology/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Neurites/metabolism/*pathology
MH  - Neurons/metabolism/*pathology
MH  - Nociception/*physiology
MH  - PC12 Cells
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Young Adult
PMC - PMC4508160
OTO - NOTNLM
OT  - CGRP
OT  - discogenic pain
OT  - human
OT  - inflammatory cytokines
OT  - intervertebral disc degeneration
OT  - nerve growth factor
EDAT- 2014/03/22 06:00
MHDA- 2015/04/14 06:00
PMCR- 2014/06/01
CRDT- 2014/03/22 06:00
PHST- 2013/12/18 00:00 [received]
PHST- 2014/01/29 00:00 [accepted]
PHST- 2014/03/22 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - 10.1111/jcmm.12268 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2014 Jun;18(6):1213-25. doi: 10.1111/jcmm.12268. Epub 2014 Mar 
      20.