Open AccessPainful, degenerating intervertebral discs up‐regulate neurite sprouting and CGRP through nociceptive factors
Author(s) -
Krock Emerson,
Rosenzweig Derek H.,
ChabotDoré AnneJulie,
Jarzem Peter,
Weber Michael H.,
Ouellet Jean A.,
Stone Laura S.,
Haglund Lisbet
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12268
Subject(s) - nerve growth factor , nociception , neurite , nociceptor , calcitonin gene related peptide , neurotrophic factors , neurotrophin , medicine , in vivo , ex vivo , inflammation , intervertebral disc , calcitonin , chronic pain , neuropeptide , anatomy , biology , in vitro , receptor , biochemistry , microbiology and biotechnology , psychiatry
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 IVD s from low back pain patients and healthy, painless IVD s from human organ donors were cultured ex vivo . Inflammatory and nociceptive factors released by IVD s 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 IVD s 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 IVD s 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 .