A common feature observed in numerous preclinical models of neuropathic pain is the development of ectopic spontaneous activity arising from primary sensory neuron somata. Importantly, this observation has been extended to occur in human dorsal root ganglion neurons, but only when these have been isolated from dermatomes with on-going neuropathic pain, underscoring the potential importance of this ectopic activity as a potentially key therapeutic target. The characteristics of ectopic SA observed in DRG neurons from experimental animals with CIPN induced by paclitaxel, oxaliplatin and bortezomib treatment will be presented here and contrasted to that observed in human DRG neurons associated with neuropathic pain. As well, data on ion channels, including voltage-gated sodium channels, calcium channels and cyclic nucleotide channels in this SA in both rodent and human DRG will be presented. Finally, the potential role of cell membrane lipid rafts in organizing this ectopic SA will be discussed.