ArticleEBioMedicine2019
Interleukin-8 as a therapeutic target for chronic low back pain: Upregulation in human cerebrospinal fluid and pre-clinical validation with chronic reparixin in the SPARC-null mouse model.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.Rheumatology (Oxford, England) · 2021Pooled it
- Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- A multifactorial intervertebral disc degeneration model: Integrating inflammation, structural disruption, biomechanical parameters, and neural sensitization.Bioengineering & translational medicine · 2026Article
- Alterations of the Cytokines, Chemokines, and Growth Factors in the Cerebrospinal Fluid of Patients with Advanced-stage Amyotrophic Lateral Sclerosis.Internal medicine (Tokyo, Japan) · 2026Article
- TRPC6-Mediated CaCells · 2026Article
- Inflammatory and Molecular Mechanisms of Adenomyosis Associated Pain: Insights from Multiple Analytic Approaches.Journal of pain research · 2026Article
- Inflammatory protein mediators linking gut microbiota to degenerative lumbar spine disorders: cross-disease genetic evidence.Frontiers in immunology · 2026Article
- An Ex Vivo Model of Intervertebral Disc Degeneration for Assessing Retention of Injectable Cell-Based Grafts.JOR spine · 2025Article
- Biological Mechanisms of Pain Management in Lumbar Disk Herniation: Focus on Cytokine Correlations and Therapeutic Approaches.International journal of molecular sciences · 2025Article
- Targeting Inflammatory Pathways in Chronic Low Back Pain: Opportunities for Novel Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2025Review
- What a pain in the back: etiology, diagnosis and future treatment directions for discogenic low back pain.Bone research · 2025Review
- Chemokines and Their Association With Symptom Severity in Women With Endometriosis.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- Serum Interleukin-8 Levels and Their Association with Anxiety and Functional Disability in Military Personnel with Chronic Low Back Pain.Journal of clinical medicine · 2025Article
- Evaluation of clinical impact of Interleukin 8 gene expression in patients with fibromyalgia.Advances in rheumatology (London, England) · 2025Article
- Investigating the epigenetic landscape of symptomatic disk degeneration: a case study.Pain reports · 2025Article
- Senolytic treatment for low back pain.Science advances · 2025Article
- The causal effects between low back pain and cerebrospinal fluid metabolites: a two-sample Mendelian randomization study.Hereditas · 2025Article
- Molecular Assessment of Plasma Concentrations of Selected Adipokines and IL-8 in Horses with Back Pain and Comorbid Asthma-Based on Clinical Cases.Animals : an open access journal from MDPI · 2025Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
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.
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