Sessions of Prolonged Continuous Theta Burst Stimulation or High-frequency 10 Hz Stimulation to Left Dorsolateral Prefrontal Cortex for 3 Days Decreased Pain Sensitivity by Modulation of the Efficacy of Conditioned Pain Modulation

Enrico De Martino; Ana Mércia Fernandes; Ricardo Galhardoni; Carolina De Oliveira Souza; Daniel Ciampi De Andrade; Thomas Graven-Nielsen

doi:10.1016/j.jpain.2019.05.010

Sessions of Prolonged Continuous Theta Burst Stimulation or High-frequency 10 Hz Stimulation to Left Dorsolateral Prefrontal Cortex for 3 Days Decreased Pain Sensitivity by Modulation of the Efficacy of Conditioned Pain Modulation

J Pain. 2019 Dec;20(12):1459-1469. doi: 10.1016/j.jpain.2019.05.010. Epub 2019 May 24.

Authors

Enrico De Martino¹, Ana Mércia Fernandes², Ricardo Galhardoni³, Carolina De Oliveira Souza⁴, Daniel Ciampi De Andrade⁵, Thomas Graven-Nielsen⁶

Affiliations

¹ Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
² Pain Center, LIM-62, Department of Neurology, University of São Paulo, São Paulo, Brazil.
³ Pain Center, LIM-62, Department of Neurology, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry (INBioN), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; School of Medicine, University of City of São Paulo (UNICID), São Paulo, Brazil.
⁴ Movement Disorders Clinic, Department of Neurology, Hospital das Clinicas of the University of São Paulo School of Medicine, São Paulo, Brazil.
⁵ Pain Center, LIM-62, Department of Neurology, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry (INBioN), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; Pain Center, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
⁶ Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark. Electronic address: [email protected].

PMID: 31132509
DOI: 10.1016/j.jpain.2019.05.010

Abstract

The 10 Hz repetitive transcranial magnetic stimulation (10 Hz-rTMS) to the left dorsolateral prefrontal cortex produces analgesia, probably by activating the pain modulation system. A newer rTMS paradigm, called theta burst stimulation (TBS), has been developed. Unlike 10 Hz-rTMS, prolonged continuous TBS (pcTBS) mimics endogenous theta rhythms, which can improve induction of synaptic long-term potentiation. Therefore, this study investigated whether pcTBS to the left dorsolateral prefrontal cortex reduced pain sensitivity more efficiently compared with 10 Hz-rTMS, the analgesic effects lasted beyond the stimulation period, and the reduced pain sensitivity was associated with increased efficacy of conditioned pain modulation (CPM) and/or intracortical excitability. Sixteen subjects participated in a randomized cross-over study with pcTBS and 10 Hz-rTMS. Pain thresholds to heat (HPT), cold, pressure (PPT), intracortical excitability assessment, and CPM with mechanical and heat supra-pain threshold test stimuli and the cold pressor test as conditioning were collected before (Baseline), 3 (Day3) and 4 days (Day4) after 3-day session of rTMS. HPTs and PPTs increased with 10 Hz-rTMS and pcTBS at Day3 and Day4 compared with Baseline (P = .007). Based on pooled data from pcTBS and 10 Hz-rTMS, the increased PPTs correlated with increased efficacy of CPM at Day3 (P = .008), while no correlations were found at Day4 or with the intracortical excitability. PERSPECTIVE: Preliminary results of this comparative study did not show stronger pain sensitivity reduction by pcTBS compared with 10 Hz-rTMS to the L-DPFC. Both protocols maintained increased pain thresholds up to 24-hours after the last session, which were partially associated with modulation of CPM efficacy but not with the intracortical excitability changes.

Keywords: Pain; conditioned pain modulation; diffuse noxious inhibitory control; dorsolateral prefrontal cortex; intracortical excitability; repetitive transcranial magnetic stimulation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cross-Over Studies
Female
Humans
Male
Pain Management / methods
Pain Threshold / physiology*
Prefrontal Cortex / physiology*
Theta Rhythm / physiology
Transcranial Magnetic Stimulation / methods*