Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

• Published in: The journal of pain Vol. 18; no. 10; pp. 1253 - 1269
• Main Authors: Lim, Tony K.Y., Anderson, Kathleen M., Hari, Pawan, Di Falco, Marcos, Reihsen, Troy E., Wilcox, George L., Belani, Kumar G., LaBoissiere, Sylvie, Pinto, Manuel R., Beebe, David S., Kehl, Lois J., Stone, Laura S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017
• Subjects: Adult; Aged; Biomarkers - cerebrospinal fluid; Cross-Sectional Studies; cystatin C; Cystatin C - cerebrospinal fluid; Female; hemopexin; Hemopexin - cerebrospinal fluid; Humans; Inflammation - cerebrospinal fluid; Inflammation - complications; intervertebral disc degeneration; Intervertebral Disc Degeneration - cerebrospinal fluid; Intervertebral Disc Degeneration - complications; Intervertebral Disc Degeneration - immunology; low back pain; Low Back Pain - cerebrospinal fluid; Low Back Pain - complications; Low Back Pain - immunology; Male; Middle Aged; Peripheral Nerve Injuries - cerebrospinal fluid; Peripheral Nerve Injuries - complications; Peripheral Nerve Injuries - immunology; Proteome; Proteomics; Young Adult; intervertebral disc degeneration; cystatin C; low back pain; Proteomics; hemopexin
• ISSN: 1526-5900; 1528-8447
• DOI: 10.1016/j.jpain.2017.06.002

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, although >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying nonpainful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy control participants, subjects with nonpainful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (eg, cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (eg, hemopexin). Cystatin C and hemopexin were selected for further examination using enzyme-linked immunosorbent assay in a larger cohort. While cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability, and DD severity. This study shows that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP. CSF was examined for differential protein expression in healthy control participants, pain-free adults with asymptomatic intervertebral DD, and LBP patients with painful intervertebral DD. While DD was related to inflammation regardless of pain status, painful degeneration was associated with markers linked to nerve injury. •Intervertebral disc degeneration alters protein expression in cerebrospinal fluid.•Pain-free disc degeneration is associated with biochemical markers of inflammation.•Painful disc degeneration is associated with biochemical markers of nerve injury.•Altered protein expression in cerebrospinal fluid can provide mechanistic insights.