• Karen Krukowski, Niels Eijkelkamp, Geoffroy Laumet, C Erik Hack, Yan Li, Patrick M Dougherty, Cobi J Heijnen, and Annemieke Kavelaars.
• Laboratory of Neuroimmunology, Division of Internal Medicine, and.
• J. Neurosci. 2016 Oct 26; 36 (43): 11074-11083.

AbstractChemotherapy-induced peripheral neuropathy (CIPN), characterized by pain and numbness in hands and feet, is a common side effect of cancer treatment. In most patients, symptoms of CIPN subside after treatment completion. However, in a substantial subgroup, CIPN persists long into survivorship. Impairment in pain resolution pathways may explain persistent CIPN. We investigated the contribution of T cells and endogenous interleukin (IL)-10 to resolution of CIPN. Paclitaxel-induced mechanical allodynia was prolonged in T-cell-deficient (Rag1-/-) mice compared with wild-type (WT) mice. There were no differences between WT and Rag1-/- mice in severity of paclitaxel-induced mechanical allodynia. Adoptive transfer of either CD3+ or CD8+, but not CD4+, T cells to Rag1-/- mice normalized resolution of CIPN. Paclitaxel treatment increased the number of T cells in lumbar dorsal root ganglia (DRG), where CD8+ T cells were the major subset. Inhibition of endogenous IL-10 signaling by intrathecal injection of anti-IL-10 to WT mice or Rag1-/- mice reconstituted with CD8+ T cells delayed recovery from paclitaxel-induced mechanical allodynia. Recovery was also delayed in IL-10 knock-out mice. Conversely, administration of exogenous IL-10 attenuated paclitaxel-induced allodynia. In vitro, IL-10 suppressed abnormal paclitaxel-induced spontaneous discharges in DRG neurons. Paclitaxel increased DRG IL-10 receptor expression and this effect requires CD8+ T cells. In conclusion, we identified a novel mechanism for resolution of CIPN that requires CD8+ T cells and endogenous IL-10. We propose that CD8+ T cells increase DRG IL-10 receptor expression and that IL-10 suppresses the abnormal paclitaxel-induced spontaneous discharges by DRG neurons to promote recovery from CIPN.Copyright © 2016 the authors 0270-6474/16/3611074-10$15.00/0.

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