AbstractBackgroundIncreasing evidence suggests that pain drives maladaptive corticomotor changes that may increase susceptibility to injury and promote symptom recurrence. However, few studies have evaluated the influence of interindividual corticomotor responses to musculoskeletal pain. Existing research in this area has also been limited largely to the upper limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb muscles, as well as the fact that most acute sporting injuries occur in the lower limb. Accordingly, this study explored the variability of corticomotor responses to experimentally‐induced sustained hamstring pain and whether specific patterns of corticomotor reorganization were associated with poorer outcomes (mechanical sensitivity, pain, or functional limitation).MethodThirty‐six healthy individuals participated. Following random allocation on Day 0, the experimental group performed an eccentric exercise protocol of the right hamstring muscles to induce delayed onset muscle soreness. The control group performed repetition‐matched concentric exercise that did not induce soreness. Measures of mechanical sensitivity, pain, function, and corticomotor organization were collected at baseline and on Day 2.Results and conclusionsCorticomotor responses to sustained hamstring pain were variable. Individuals who developed corticomotor facilitation in response to hamstring pain experienced greater mechanical sensitivity than those who developed corticomotor depression. These novel data could have implications for rehabilitation following lower limb pain or injury.