88. Contribution of peripheral immune cells to chemotherapy-induced neuropathy

Abstract

Peripheral neuropathy characterized by pain and numbness is a common side effect of chemotherapy. In rodent models of chemotherapy-induced peripheral neuropathy (CIPN) increased sensitivity to a mechanical stimulus (mechanical hyperalgesia) is a common read out of pain. Unfortunately, studies of sensorimotor deficits in CIPN are limited because of insufficient animal behavioral assessment tools. Developing a tool, the adhesive removal test (ART), to quantify sensory deficits was the first aim of this study. Chemotherapy induced pro-inflammatory responses may contribute to CIPN. Therefore the second aim was to investigate potential contributions of infiltrating peripheral leukocytes into the dorsal root ganglia (DRG) during CIPN. Chemotherapeutic agents increased mechanical hyperalgesia (von Frey) and increased sensorimotor deficits (ART) in mice when compared to vehicle-treated mice. Increased CD45 + leukocytes in the DRG were also associated with CIPN, suggesting a role for these leukocytes in CIPN. In chemotherapy-treated wild type mice, hyperalgesia subsided approximately 14 days after treatment whereas in immune-deficient mice (Rag1-/-) hyperalgesia persisted for longer (21 days). Rag1-/- mice lack functional adaptive immune cells, suggesting a role for these leukocytes in CIPN. Findings of leukocyte infiltration have been observed in models of nerve injury, but to our knowledge this is the first time that CD45 + leukocyte infiltration has been associated with CIPN. Further investigation into the role of infiltrating leukocyte subpopulations in the DRG will provide insights into mechanisms underlying CIPN.