Heat-evoked experimental pain induces long-term potentiation-like plasticity in human primary motor cortex

A. Suppa, A. Biasiotta, D. Belvisi, L. Marsili, S. La Cesa, A. Truini, G. Cruccu, A. Berardelli

Research output: Contribution to journalArticlepeer-review


We designed a new paired associative stimulation (PAS) protocol that combines experimental pain evoked by laser stimuli and transcranial magnetic stimulation (TMS) (Laser-PAS) to primary motor cortex (M1). We tested in healthy subjects whether Laser-PAS elicits cortical plasticity as reflected by long-term changes in motor-evoked potentials (MEPs) (after-effects). In separate experiments, we examined numerous variables including changes induced by varying the interstimulus intervals (ISIs) and Laser-PAS-induced changes in target and non-target muscle MEPs. We measured MEPs after repetitive laser or TMS (rTMS) pulses, and compared magnetic- and electric (TES)-induced MEPs. We tested MEPs after applying Laser-PAS with laser pulses ipsilaterally to M1. Finally, we studied subjects receiving an N-methyl-d-aspartate (NMDA) receptor antagonist (memantine) or placebo (α-lipoic acid). During Laser-PAS at the 50 ms ISI MEPs decreased, thereafter they increased for 60 min; other ISIs induced no after-effects. The after-effects remained restricted to the target muscle. Repetitive laser pulses and rTMS induced no after-effects. After Laser-PAS, TMS-induced MEPs increased, whereas TES-induced MEPs did not. Laser-PAS with laser pulses ipsilaterally to M1 left MEPs unchanged. Memantine, but not α-lipoic acid, abolished the after-effects. In conclusion, Laser-PAS elicits NMDA-dependent cortical plasticity and provides new insights into human pain-motor integration.

Original languageEnglish
Pages (from-to)1942-1951
Number of pages10
JournalCerebral Cortex
Issue number8
Publication statusPublished - Aug 2013


  • laser-evoked potentials
  • pain-motor integration
  • primary motor cortex
  • spike timing-dependent plasticity
  • TMS

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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