Understanding intracortical excitability in phantom limb pain: A multivariate analysis from a multicenter randomized clinical trial

Neurophysiol Clin. 2021 Mar;51(2):161-173. doi: 10.1016/j.neucli.2020.12.006. Epub 2021 Feb 26.


Objectives: To explore associations of intracortical excitability with clinical characteristics in a large sample of subjects with phantom limb pain (PLP).

Methods: Ancillary study using baseline and longitudinal data from a large multicenter randomized trial that investigated the effects of non-invasive brain stimulation combined with sensorimotor training on PLP. Multivariate regression modeling analyses were used to investigate the association of intracortical excitability, measured by percentages of intracortical inhibition (ICI) and facilitation (ICF) with clinical variables.

Results: Ninety-eight subjects were included. Phantom sensation of itching was positively associated with ICI changes and at baseline in the affected hemisphere (contralateral to PLP). However, in the non-affected hemisphere (ipsilateral to PLP), the phantom sensation of warmth and PLP intensity were negatively associated with ICI (both models). For the ICF, PLP intensity (baseline model only) and age (longitudinal model) were negatively associated, while time since amputation and amputation level (both for longitudinal model only) were positively associated in the affected hemisphere. Additionally, use of antidepressants led to lower ICF in the non-affected hemisphere for the baseline model while higher amputation level also led to less changes in the ICF.

Conclusion: Results revealed clear associations of clinical variables and cortical excitability in a large chronic pain sample. ICI and ICF changes appear not to be mainly explained by PLP intensity. Instead, other variables associated with duration of neuroplasticity changes (such as age and duration of amputation) and compensatory mechanisms (such as itching and phantom limb sensation) seem to be more important in explaining these variables.

Keywords: Chronic pain; Cortex excitability; Intracortical facilitation; Intracortical inhibition; Phantom limb pain.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Amputation
  • Cortical Excitability
  • Humans
  • Multivariate Analysis
  • Phantom Limb*
  • Sensation