• Emerson Krock, Magali Millecamps, Kathleen M Anderson, Akanksha Srivastava, Troy E Reihsen, Pawan Hari, Yue Ran Sun, Seon Ho Jang, George L Wilcox, Kumar G Belani, David S Beebe, Jean Ouellet, Manuel R Pinto, Lois J Kehl, Lisbet Haglund, and Laura S Stone.
• Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec H3A 0G1, Canada; McGill Scoliosis and Spine Research Group, McGill University, Montreal, Quebec H3A 1G1, Canada; Faculty of Medicine, Department of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Quebec H3A 1G1, Canada. Electronic address: emerson.krock@ki.se.
• EBioMedicine. 2019 May 1; 43: 487-500.

BackgroundLow back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study.MethodsPain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array.FindingsIL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice.InterpretationThese studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. FUND: Supported by NIH, MMF, CIHR and FRQS.Copyright © 2019. Published by Elsevier B.V.

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