Review of the Role of the Brain in Chemotherapy-Induced Peripheral Neuropathy.

Maryam Omran,Michelle C Janelsins,Elizabeth K Belcher,Shelli R Kesler,Andrea G Hohmann,Ian R Kleckner,Nimish A Mohile

doi:10.3389/fmolb.2021.693133

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating, and dose-limiting side effect of many chemotherapy regimens yet has limited treatments due to incomplete knowledge of its pathophysiology. Research on the pathophysiology of CIPN has focused on peripheral nerves because CIPN symptoms are felt in the hands and feet. However, better understanding the role of the brain in CIPN may accelerate understanding, diagnosing, and treating CIPN. The goals of this review are to (1) investigate the role of the brain in CIPN, and (2) use this knowledge to inform future research and treatment of CIPN. We identified 16 papers using brain interventions in animal models of CIPN and five papers using brain imaging in humans or monkeys with CIPN. These studies suggest that CIPN is partly caused by (1) brain hyperactivity, (2) reduced GABAergic inhibition, (3) neuroinflammation, and (4) overactivation of GPCR/MAPK pathways. These four features were observed in several brain regions including the thalamus, periaqueductal gray, anterior cingulate cortex, somatosensory cortex, and insula. We discuss how to leverage this knowledge for future preclinical research, clinical research, and brain-based treatments for CIPN.

Highlights

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and severe toxicity of many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogues (Staff et al, 2017; Chan et al, 2019)
We investigated the hypothesis that the brain plays a prominent or even causal role in CIPN by reviewing the literature on experimental manipulations of the brain to see its effect on CIPN in nonhuman animals
Our review implicated four common themes related to the role of the brain in CIPN, with brain hyperactivity being a key feature of the pathology of CIPN

Summary

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and severe toxicity of many widely used chemotherapy drugs including platinum-based agents (oxaliplatin, cisplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids, proteasome inhibitors, and thalidomide analogues (Staff et al, 2017; Chan et al, 2019). These neurotoxic anti-cancer agents are used to treat breast, lung, cervical, prostate, ovarian, testicular, gastrointestinal, and blood or bone marrow cancers. CIPN can severely impair physical, social, emotional, functional, financial, and occupational aspects of life

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