Spinal activity of interleukin 6 mediates myelin basic protein-induced allodynia.

Brain Behav Immun

Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, La Jolla, CA, USA. Electronic address:

Published: August 2016

AI Article Synopsis

  • Mechanosensory fibers are surrounded by myelin, which allows for quick signal transmission; damage to myelin can cause mechanical allodynia, a painful response to normally non-painful stimuli.
  • A study found that injecting a specific peptide (MBP84-104) into the sciatic nerve of rats led to long-lasting allodynia, requiring T cells and significantly increasing levels of interleukin-6 (IL-6) in the spinal cord.
  • Systemic gabapentin was effective in relieving this allodynia, while other treatments like ketorolac and lidocaine were not; blocking IL-6 also reduced the pain, suggesting that IL-6 plays a key role in pain processing related to my

Article Abstract

Mechanosensory fibers are enveloped by myelin, a unique multilamellar membrane permitting saltatory neuronal conduction. Damage to myelin is thought to contribute to severe pain evoked by innocuous tactile stimulation (i.e., mechanical allodynia). Our earlier (Liu et al., 2012) and present data demonstrate that a single injection of a myelin basic protein-derived peptide (MBP84-104) into an intact sciatic nerve produces a robust and long-lasting (>30days) mechanical allodynia in female rats. The MBP84-104 peptide represents the immunodominant epitope and requires T cells to maintain allodynia. Surprisingly, only systemic gabapentin (a ligand of voltage-gated calcium channel α2δ1), but not ketorolac (COX inhibitor), lidocaine (sodium channel blocker) or MK801 (NMDA antagonist) reverse allodynia induced by the intrasciatic MBP84-104. The genome-wide transcriptional profiling of the sciatic nerve followed by the bioinformatics analyses of the expression changes identified interleukin (IL)-6 as the major cytokine induced by MBP84-104 in both the control and athymic T cell-deficient nude rats. The intrasciatic MBP84-104 injection resulted in both unilateral allodynia and unilateral IL-6 increase the segmental spinal cord (neurons and astrocytes). An intrathecal delivery of a function-blocking IL-6 antibody reduced the allodynia in part by the transcriptional effects in large-diameter primary afferents in DRG. Our data suggest that MBP regulates IL-6 expression in the nervous system and that the spinal IL-6 activity mediates nociceptive processing stimulated by the MBP epitopes released after damage or disease of the somatosensory nervous system.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917441PMC
http://dx.doi.org/10.1016/j.bbi.2016.03.003DOI Listing

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