Mechanisms of Neuromuscular Fatigability in People with Cancer-Related Fatigue

Med Sci Sports Exerc. 2022 Aug 1;54(8):1355-1363. doi: 10.1249/MSS.0000000000002919. Epub 2022 Apr 8.


Introduction: Cancer-related fatigue (CRF) is a debilitating symptom that affects around one-third of people for months or years after cancer treatment. In a recent study, we found that people with posttreatment CRF have greater neuromuscular fatigability. The aim of this secondary analysis was to examine the etiology of neuromuscular fatigability in people with posttreatment CRF.

Methods: Ninety-six people who had completed cancer treatment were dichotomized into two groups (fatigued and nonfatigued) based on a clinical cut point for fatigue. Alterations in neuromuscular function (maximal voluntary contraction peak force, voluntary activation, potentiated twitch force, and EMG) in the knee extensors were assessed across three common stages of an incremental cycling test. Power outputs during the fatigability test were expressed relative to gas exchange thresholds to assess relative exercise intensity.

Results: The fatigued group had a more pronounced reduction in maximal voluntary contraction peak force and potentiated twitch force throughout the common stages of the incremental cycling test (main effect of group: P < 0.001, ηp2 = 0.18 and P = 0.029, ηp2 = 0.06, respectively). EMG was higher during cycling in the fatigued group (main effect of group: P = 0.022, ηp2 = 0.07). Although the relative intensity of cycling was higher in the fatigued group at the final common stage of cycling, this was not the case during the initial two stages, despite the greater impairments in neuromuscular function.

Conclusions: Our results suggest that the rapid impairments in neuromuscular fatigability in people with CRF were primarily due to disturbances at the level of the muscle rather than the central nervous system. This could affect the ability to tolerate daily physical activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electromyography / methods
  • Fatigue / etiology
  • Humans
  • Knee / physiology
  • Muscle Contraction / physiology
  • Muscle Fatigue* / physiology
  • Muscle, Skeletal / physiology
  • Neoplasms* / complications