Paclitaxel-Resistant Neurons in Dorsal Root Ganglia

Paclitaxel is an antineoplastic drug, and its usage is often limited by severe peripheral polyneuropathy characterized by symptoms in remote extremities. It is suggested that subpopulations of dorsal root ganglion (DRG) neurons are impacted functionally and/or structurally. In this study, the neurotoxic effect of this drug in cultured rat DRG neurons was analyzed by measuring their neurite length and electrophysiological properties. It was observed that exposure of the cultured DRG neurons to 3, 10 and 30 μM paclitaxel for 24 or 48h caused a dose-dependent shortening of length or loss of neurite, typically in the “dying back” pattern. Eight of 28 large DRG neuron populations with extensive neurites showed less sensitivity or were entirely resistant to paclitaxel treatment. Whole-cell patch clamp experiments revealed that these paclitaxel-resistant neurons may fall in the category of Aδ or Aβ neurons. Deeper understanding as to why this particular subclass of neurons is resistant could reveal novel approaches to protect the primary sensory neurons from chemotherapy agent-induced toxicity and screening methods to identify chemical agents that will not induce peripheral neuropathy in cancer patients.