Elevated inflammatory cytokine expression in CSF from patients with symptomatic thoracic disc herniation correlates with increased pain scores

Spine J. 2018 Dec;18(12):2316-2322. doi: 10.1016/j.spinee.2018.07.023. Epub 2018 Aug 2.

Abstract

Background: The pathophysiology of pain in patients with symptomatic thoracic disc herniation (TDH) remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniation. A similar correlation in patients with TDH has not been investigated.

Purpose: To correlate the cerebrospinal fluid (CSF) expression of cytokines and pain-related amino acids with preoperative pain scores in patients with symptomatic TDH.

Study design: A prospective human study of CSF samples and clinical outcome scores.

Methods: Using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), we determined inflammatory cytokine levels (TNF-α, IL-1β, and IL-10) and amino acid levels (glutamate, aspartate, gamma-aminobutyric acid, glycine, and arginine) in CSF samples from 10 patients with TDH and 10 control subjects who did not suffer an inflammatory disease nor pain related to spinal cord compression and subsequently correlated these levels with preoperative pain scores. Differences between both groups were evaluated by a Mann-Whitney U test. In order to estimate the correlation between cytokine or amino acid expression and pain scores, data were analyzed using a linear regression analysis.

Results: No inflammatory cytokines were found in CSF samples from control subjects, whereas TNF-α, IL-1β, and IL-10 were detectable by ELISA in all CSF samples from patients with TDH. TNF-α and IL-10 but not IL-1β levels moderately correlated with preoperative pain scores. Elevated TNF-αlevels positively correlated with high pain scores; elevated IL-10 levels negatively correlated with high pain scores. Amino acids were detectable in all samples from both groups. There were no significant differences between the groups in any of the amino acids measured with HPLC.

Conclusion: Increased proinflammatory cytokine expression is associated with elevated pain scores in patients with symptomatic TDH. On the other hand, there is no conclusive correlation between the intensity of pain and the local or systemic presence of amino acids associated with pain transmission.

Keywords: Cerebrospinal fluid; IL-10; IL-1β; Neuropathic pain; TNF-α; Thoracic disc herniation.

MeSH terms

  • Adult
  • Aged
  • Amino Acids / cerebrospinal fluid
  • Female
  • Humans
  • Interleukin-10 / cerebrospinal fluid*
  • Interleukin-1beta / cerebrospinal fluid*
  • Intervertebral Disc Displacement / metabolism*
  • Male
  • Middle Aged
  • Neuralgia / metabolism*
  • Preoperative Period
  • Prospective Studies
  • Regression Analysis
  • Thoracic Vertebrae*
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid*

Substances

  • Amino Acids
  • IL10 protein, human
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10