Treatment of established chemotherapy-induced peripheral neuropathy: Basic science and animal models

Advancement of effective therapies to treat established CIPN will require a deeper understanding of CIPN pathomechanisms. Simplified models of CIPN have been developed using whole-animal systems, primary cultures, and immortalized cell lines to allow for detailed mechanistic studies. Recently, human stem-cell derived neuronal cultures have also allowed new opportunities to study CIPN. In this chapter, we provide an overview of studies that used model systems to investigate the treatment of established CIPN. We have divided the chapter into two main areas. First, there are studies that investigate CIPN-related nerve damage through the lens of neurogenesis, Schwann cells, and axonal regrowth. Next, we review model approaches to treat CIPN-related pain that have focused on voltage-gated ion channels, neuroinflammation, sphingosine metabolism, and endocannabinoids. The broad approaches that are being employed to study the treatment of established CIPN in model systems provide hope for future beneficial therapeutics.