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

Paulo E P Teixeira; Kevin Pacheco-Barrios; Muhammed Enes Gunduz; Anna Carolyna Gianlorenço; Luis Castelo-Branco; Felipe Fregni

doi:10.1016/j.neucli.2020.12.006

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.

Authors

Paulo E P Teixeira¹, Kevin Pacheco-Barrios², Muhammed Enes Gunduz³, Anna Carolyna Gianlorenço⁴, Luis Castelo-Branco³, Felipe Fregni⁵

Affiliations

¹ Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; MGH Institute of Health Professions, Boston, MA, USA; Instituto Wilson Mello, Campinas, SP, Brazil. Electronic address: pteixeira2@mgh.harvard.edu.
² Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru.
³ Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
⁴ Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Laboratory of neuroscience, Department of Physical Therapy, Federal University of Sao Carlos, SP, Brazil.
⁵ Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Abstract

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, Surgical
Cortical Excitability
Humans
Multivariate Analysis
Phantom Limb*
Sensation

Grants and funding

R01 HD082302/HD/NICHD NIH HHS/United States