Inflammatory Neuropathy in Mouse and Primate Models of Colorectal Cancer

Although pre-existing neuropathy is a risk factor for chronic pain, tumor-induced neuropathy has not been firmly established in pre-clinical models. Consistent with clinical observations, we show that mice with colorectal cancer develop peripheral neuropathy, which was associated with subtle locomotor deficits, without overt hypersensitivity.

We detected widespread differences in pro-inflammatory cytokines and lipid metabolites in peripheral nerves from tumor-bearing mice. Macrophage accumulation, myelin decompaction and ryanodine receptor oxidation were associated with dysfunctional calcium homeostasis and reduced spike amplitude in sensory neurons. Similar alterations in plasma inflammatory mediators and lipid metabolites were associated with neuropathy and macrophage accumulation in peripheral nerves of rhesus macaques with colorectal cancer.