Inhibition of IL-6 signaling: A novel therapeutic approach to treating spinal cord injury pain

Pain. 2013 Jul;154(7):1115-28. doi: 10.1016/j.pain.2013.03.026. Epub 2013 Mar 21.


To characterize the contribution of interleukin-6 (IL-6) to spinal cord injury pain (SCIP), we employed a clinically relevant rat contusion model of SCIP. Using Western blots, we measured IL-6 levels in lumbar segments (L1-L5), at the lesion site (T10), and in the corresponding lumbar and thoracic dorsal root ganglia (DRG) in 2 groups of similarly injured rats: (a) SCI rats that developed hind-limb mechanical allodynia (SCIP), and (b) SCI rats that did not develop SCIP. Only in SCIP rats did we find significantly increased IL-6 levels. Immunocytochemistry showed elevated IL-6 predominantly in reactive astrocytes. Our data also showed that increased production of IL-6 in hyperreactive astrocytes in SCIP rats may explain still-poorly understood astrocytic contribution to SCIP. To test the hypothesis that IL-6 contributes to mechanical allodynia, we treated SCIP rats with neutralizing IL-6 receptor antibody (IL-6-R Ab), and found that one systemic injection abolished allodynia and associated weight loss; in contrast to gabapentin, the analgesic effect lasted for at least 2weeks after the injection, despite the shorter presence of the Ab in the circulation. We also showed that IL-6-R Ab partially reversed SCI-induced decreases in the protein levels of the glutamate transporter GLT-1 12hours and 8days after Ab injection, which may explain the lasting analgesic effect of the Ab in SCIP rats. A link between reactive astrocytes IL-6-GLT-1 has not been previously shown. Given that the humanized IL-6-R Ab tocilizumab is Food and Drug Administration-approved for rheumatoid arthritis, we are proposing tocilizumab as a novel and potentially effective treatment for SCIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism*
  • Interleukin-6 / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / physiopathology*
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • tocilizumab