Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it is becoming more critical to develop mechanistic understanding of the effects of exercise in order to tailor it to best treat CIPN symptoms and identify who will benefit most. To address the current lack of clarity around the effect of exercise on CIPN, we reviewed the key potential mechanisms (e.g., neurophysiological and psychosocial factors), mediators (e.g., anti-inflammatory cytokines, self-efficacy, and social support), and moderators (e.g., age, sex, body mass index, physical fitness, exercise dose, exercise adherence, and timing of exercise) that may illuminate the relationship between exercise and CIPN improvement. Our review is based on the studies that tested the use of exercise for patients with CIPN, patients with other types of neuropathies, and healthy adults. The discussion presented herein may be used to (1) guide oncologists in predicting which symptoms are best targeted by specific exercise programs, (2) enable clinicians to tailor exercise prescriptions to patients based on specific characteristics, and (3) inform future research and biomarkers on the relationship between exercise and CIPN.

Mechanisms of Paclitaxel-induced peripheral neuropathy

“…Herein, we provided an overview of the recent findings of the possible targets implicated in PIPN which include; dysfunction of axonal transport, mitochondrial dysfunction, activation of immune system, hyperexcitability of the axons as well as the role of lipid metabolites as shown in Figure 1. Although, medications based on these mechanisms and a variety of techniques has shown some neuroprotective effect against PIPN in experimental setting and clinical settings such as acupuncture [140], cryotherapy [141], compression therapy [142], exercise therapy [143], scrambler therapy [144]. In addition to a plethora of natural products and clinically used drugs including all-trans retinoic acid [145], amifostine [146], cannabinoids [147], goshajinkigan [148], metformin [149], minocycline [150], pregabalin [151], and venlafaxine [152].…”

Non-Pharmacological Self-Management Strategies for Chemotherapy-Induced Peripheral Neuropathy in People with Advanced Cancer: A Systematic Review and Meta-Analysis

“…These beneficial effects of exercise on CIPN are supported by mechanistic studies. For example, exercise counteracts the deleterious effects of chemotherapy on the nervous system central to CIPN by reducing inflammation, suppressing pain pathways, and enhancing neuroprotective factors involved in the development, survival, and function of neurons [46,47]. In addition, exercise has broader health benefits for people with advanced cancer, such as improved quality of life, fatigue, body composition, psychosocial function, and sleep quality, and it appears safe when implemented on advice from a health professional [48].…”

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy

“…We did not investigate prediagnosis physical activity, which has been shown to correlate with posttreatment physical activity regardless of symptoms and barriers presented 49 . Further, it is also plausible that other factors, including social support and self‐efficacy, are key moderators of physical activity behavior 20 …”