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The nociceptive flexion reflex (NFR) is a spinally-mediated withdrawal reflex occurring in response to noxious stimuli and is used as an electrophysiological marker of spinal nociception. Although it is well-documented that the NFR is subject to powerful modulation of several personal factors, the effects of experimentally induced fatigue on the NFR have not yet been examined. Hence, this study aimed to characterize if and how fatigue affects spinal nociception in healthy adults. The NFR of 58 healthy people was measured prior to and fol