Xavier Moisset1, Simon Goudeau2, Frédérique Poindessous-Jazat3, Sophie Baudic3, Pierre Clavelou4, Didier Bouhassira3. 1. INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, F-92100 Boulogne Billancourt, France; Clermont Université, Université d'Auvergne, Neuro-Dol, Inserm U-1107, F-63000 Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Service de Neurologie, CHU Gabriel Montpied, F-63000 Clermont-Ferrand, France. Electronic address: xavier.moisset@gmail.com. 2. INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, F-92100 Boulogne Billancourt, France; Faculté de pharmacie, Université de Poitiers, France. 3. INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, F-92100 Boulogne Billancourt, France; Université Versailles-Saint-Quentin, Versailles F-78035, France. 4. Clermont Université, Université d'Auvergne, Neuro-Dol, Inserm U-1107, F-63000 Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Service de Neurologie, CHU Gabriel Montpied, F-63000 Clermont-Ferrand, France.
Abstract
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) at high frequency (>5 Hz) induces analgesic effects, probably by activating pain modulation systems. A new rTMS paradigm--theta burst stimulation (TBS)--consists of bursts of three pulses at 50 Hz repeated five times per second. Like high frequency rTMS, both intermittent and prolonged continuous TBS (iTBS and pcTBS) lead to a facilitation of cortical excitability. OBJECTIVES: (1) to evaluate the analgesic effects of neuronavigated iTBS and pcTBS, comparing them with those of classical high frequency rTMS (10 Hz) over the left M1, (2) to elucidate the role of conditioned pain modulation (CPM) in the antinociceptive effect of rTMS and (3) to investigate possible correlations between analgesia and cortical excitability. METHODS: Fourteen healthy volunteers participated in four experimental sessions, carried out in a random order (iTBS, pcTBS, 10 Hz rTMS or sham). Cold pain threshold, CPM and cortical excitability measurements were carried out before and after rTMS. RESULTS: We found that the analgesic effects of 10 Hz rTMS and pcTBS were significantly superior to those of sham rTMS. Moreover, pcTBS was significantly more effective than 10 Hz rTMS (P = 0.026). Analgesia did not seem to be driven by changes in CPM or cortical excitability. CONCLUSION: Prolonged cTBS has considerable clinical potential, as it has a shorter treatment duration (by a factor 8) and stronger analgesic effects than the classical high frequency protocol. Studies in patients are required to confirm the potential of this new stimulation paradigm for clinical applications.
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) at high frequency (>5 Hz) induces analgesic effects, probably by activating pain modulation systems. A new rTMS paradigm--theta burst stimulation (TBS)--consists of bursts of three pulses at 50 Hz repeated five times per second. Like high frequency rTMS, both intermittent and prolonged continuous TBS (iTBS and pcTBS) lead to a facilitation of cortical excitability. OBJECTIVES: (1) to evaluate the analgesic effects of neuronavigatediTBS and pcTBS, comparing them with those of classical high frequency rTMS (10 Hz) over the left M1, (2) to elucidate the role of conditioned pain modulation (CPM) in the antinociceptive effect of rTMS and (3) to investigate possible correlations between analgesia and cortical excitability. METHODS: Fourteen healthy volunteers participated in four experimental sessions, carried out in a random order (iTBS, pcTBS, 10 Hz rTMS or sham). Cold pain threshold, CPM and cortical excitability measurements were carried out before and after rTMS. RESULTS: We found that the analgesic effects of 10 Hz rTMS and pcTBS were significantly superior to those of sham rTMS. Moreover, pcTBS was significantly more effective than 10 Hz rTMS (P = 0.026). Analgesia did not seem to be driven by changes in CPM or cortical excitability. CONCLUSION: Prolonged cTBS has considerable clinical potential, as it has a shorter treatment duration (by a factor 8) and stronger analgesic effects than the classical high frequency protocol. Studies in patients are required to confirm the potential of this new stimulation paradigm for clinical applications.
Authors: Stefano Giannoni-Luza; Kevin Pacheco-Barrios; Alejandra Cardenas-Rojas; Piero F Mejia-Pando; Maria A Luna-Cuadros; Judah L Barouh; Marina Gnoatto-Medeiros; Ludmilla Candido-Santos; Alice Barra; Wolnei Caumo; Felipe Fregni Journal: Pain Date: 2020-09-01 Impact factor: 7.926