Mechanisms involved in the development of chemotherapy-induced neuropathy

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition seen in patients undergoing treatment with common agents such as vincristine, paclitaxel, oxaliplatin and bortezomib. The mechanisms of this condition are diverse, and include an array of molecular and cellular contributions. Current research implicates genetic predispositions to this condition, which then may influence cellular responses to chemotherapy. Processes found to be influenced during CIPN include increased expression of inflammatory mediators, primarily cytokines, which can create cascading effects in neurons and glia. Changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures have been implicated in CIPN. This review explores these issues and suggests considerations for future research.

Keywords: chemotherapy; cytokine; glial cells; ion channels; neuropathy; neurotransmission.

Figure 1. Schematic overview of mechanisms of chemotherapy-induced peripheral neuropathy

(A) Illustrates neuronal and glial targets for chemotherapeutics, including paclitaxel, bortezomib and oxaliplatin. (B) Indicates the mulitple ways these drugs alter neuron and glial cell function, resulting in activation of astrocytes, enhanced cytokine release, mitotoxicity and eventual apoptosis, spontaneous discharge and altered signaling in primary afferent fibers, and loss of cutaneous fibers, ultimately enhancing nociceptive input. CIPN: Chemotherapy-induced peripheral neuropathy; DRG: Dorsal root ganglion; ROS: Reactive oxygen species; TLR: Toll-like receptor; TRP: Transient receptor potential.