A Randomized,Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial |
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| Authors: | Juhani Ojala Jukka Vanhanen Hanna Harno Pantelis Lioumis Selja Vaalto Mari A. Kaunisto Jukka Putaala Marko Kangasniemi Erika Kirveskari Jyrki P. Mäkelä Eija Kalso |
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| Affiliation: | 1. Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;2. HUS Diagnostic Center, Clinical Neurophysiology, Clinical Neurosciences, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;3. BioMag Laboratory, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;4. Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;5. Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland;6. Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland;7. HUS Diagnostic Center, Department of Radiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland |
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| Abstract: | ObjectivesCentral poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.Materials and MethodsThis prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.ResultsWe prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.ConclusionsS2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study. |
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| Keywords: | Central poststroke pain conditioned pain modulation CPM CPSP pain genetics primary motor cortex secondary somatosensory cortex transcranial magnetic stimulation |
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