Effects of pain on cortical homeostatic plasticity in humans: a systematic review

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Homeostatic plasticity (HP) is a negative feedback mechanism that prevents excessive facilitation or depression of cortical excitability (CE). Cortical HP responses in humans have been investigated by using 2 blocks of noninvasive brain stimulation with a no-stimulation block in between. A healthy HP response is characterized by reduced CE after 2 excitatory stimulation blocks and increased CE when using inhibitory stimulation. Conversely, impaired HP responses have been demonstrated in experimental and chronic pain conditions. Therefore, this systematic review aimed to provide an overview of the effect of pain on cortical HP in humans. Scopus, Embase, and PubMed were searched from inception until November 20, 2023. The included studies (1) compared experimental or clinical pain conditions with healthy controls, (2) induced HP using 2 blocks of stimulation with a no-stimulation interval, and (3) evaluated CE measures such as motor-evoked potentials. Four studies were included, consisting of 5 experiments and 146 participants, of whom 63 were patients with chronic pain and 48 were subjected to an experimental pain model. This systematic review found support for an HP impairment in pain compared with that in pain-free states, reflected by a lack of CE reduction after excitatory-excitatory HP induction over the primary motor cortex. Inhibitory-inhibitory HP induction did not produce a consistent HP response across studies, independent of pain or pain-free states. Standardization of HP induction protocols and outcome calculations is needed to ensure reproducibility and study comparison. Future HP studies may consider investigating sensory domains including nociception, which would further our understanding of abnormal HP regulation in pain conditions.

Original languageEnglish
Article numbere1141
JournalPain Reports
Issue number2
Pages (from-to)E1141
Publication statusPublished - 4 Apr 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.


  • Corticomotor excitability
  • Homeostatic plasticity
  • Noninvasive brain stimulation
  • Pain
  • Plasticity


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