Highlights
- •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.
Abstract
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.
Perspective
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.
Key words
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Article info
Publication history
Published online: June 24, 2017
Accepted:
June 8,
2017
Received in revised form:
June 8,
2017
Received:
October 31,
2016
Footnotes
Supported by grants from the National Institutes for Health (R21 DA020108) and the Minnesota Medical Foundation to L.K. and L.S.S., the Canadian Institutes of Health Research/Canadian Pain Society/Astrazeneca Biology of Pain Young Investigators Operating Grant XCP-83755, and CIHR Operating Grant MOP-126046 to L.S.S., the Canadian Foundation for Innovation and the Quebec Network for Oral and Bone Health Research for Infrastructure support to L.S.S. and T.K.Y.L., and the Fonds de la recherche en sante Quebec Salary Award (Bourse de chercheur-boursier “Junior 2”) to L.S.S. The sponsors had no role in the study design, collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
The authors have no conflicts of interest to declare.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
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© 2017 Published by Elsevier Inc. on behalf of the American Pain Society
