Cancer-Related Fatigue: Central or Peripheral?

To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P < 0.001), a shorter ET (P < 0.001), and a greater TF with the SC (CRF > controls, P < 0.05). This indicated less muscle fatigue. There was a greater TF (P < 0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P < 0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.