• Sonia Betti, Marco Badioli, Daniela Dalbagno, Sara Garofalo, Giuseppe di Pellegrino, and Francesca Starita.
• Department of Psychology "Renzo Canestrari," Center for Studies and Research in Cognitive Neuroscience, University of Bologna, Cesena, Italy.
• Pain. 2024 Jun 22.

AbstractPain-related motor adaptations may be enacted predictively at the mere threat of pain, before pain occurrence. Yet, in humans, the neurophysiological mechanisms underlying motor adaptations in anticipation of pain remain poorly understood. We tracked the evolution of changes in corticospinal excitability (CSE) as healthy adults learned to anticipate the occurrence of lateralized, muscle-specific pain to the upper limb. Using a Pavlovian threat conditioning task, different visual stimuli predicted pain to the right or left forearm (experiment 1) or hand (experiment 2). During stimuli presentation before pain occurrence, single-pulse transcranial magnetic stimulation was applied over the left primary motor cortex to probe CSE and elicit motor evoked potentials from target right forearm and hand muscles. The correlation between participants' trait anxiety and CSE was also assessed. Results showed that threat of pain triggered corticospinal inhibition specifically in the limb where pain was expected. In addition, corticospinal inhibition was modulated relative to the threatened muscle, with threat of pain to the forearm inhibiting the forearm and hand muscles, whereas threat of pain to the hand inhibited the hand muscle only. Finally, stronger corticospinal inhibition correlated with greater trait anxiety. These results advance the mechanistic understanding of pain processes showing that pain-related motor adaptations are enacted at the mere threat of pain, as sets of anticipatory, topographically organized motor changes that are associated with the expected pain and are shaped by individual anxiety levels. Including such anticipatory motor changes into models of pain may lead to new treatments for pain-related disorders.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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