Understanding intracortical excitability in phantom limb pain: A multivariate analysis from a multicenter randomized clinical trial - 27/02/21

Doi : 10.1016/j.neucli.2020.12.006

Paulo E.P. Teixeira ^a,^b,^c,^d,⁎ , Kevin Pacheco-Barrios ^a,^b,^e, Muhammed Enes Gunduz ^a,^b, Anna Carolyna Gianlorenço ^a,^b,^f, Luis Castelo-Branco ^a,^b, Felipe Fregni ^a,^b,^g
^a Neuromodulation and Clinical Research Learning Center, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA
^b Harvard Medical School, Boston, MA, USA
^c MGH Institute of Health Professions, Boston, MA, USA
^d Instituto Wilson Mello, Campinas, SP, Brazil
^e Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru
^f Laboratory of neuroscience, Department of Physical Therapy, Federal University of Sao Carlos, SP, Brazil
^g Harvard T. H. Chan School of Public Health, Boston, MA, USA

^⁎Corresponding author at: Neuromodulation Center and Center for Clinical Research Learning, 79/96 13th Street – 1st Floor, Suite 105, Charlestown, MA 02129, USA.Neuromodulation Center and Center for Clinical Research Learning79/96 13th Street – 1st Floor, Suite 105CharlestownMA02129USA

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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.

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Keywords : Chronic pain, Cortex excitability, Intracortical facilitation, Intracortical inhibition, Phantom limb pain