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April 30, 2019; 92 (18) Null Hypothesis

Insular and anterior cingulate cortex deep stimulation for central neuropathic pain

Disassembling the percept of pain

View ORCID ProfileRicardo Galhardoni, Valquíria Aparecida da Silva, Luís García-Larrea, View ORCID ProfileCamila Dale, View ORCID ProfileAbrahão F. Baptista, Luciana Mendonça Barbosa, Luciana Mendes Bahia Menezes, Silvia R.D.T. de Siqueira, Fernanda Valério, Jefferson Rosi, Antonia Lilian de Lima Rodrigues, Diego Toledo Reis Mendes Fernandes, Priscila Mara Lorencini Selingardi, View ORCID ProfileMarco Antônio Marcolin, Fábio Luís de Souza Duran, Carla Rachel Ono, View ORCID ProfileLeandro Tavares Lucato, Ana Mércia B. L. Fernandes, Fábio E. F. da Silva, Lin T. Yeng, André R. Brunoni, Carlos A. Buchpiguel, Manoel J. Teixeira, Daniel Ciampi de Andrade
First published April 5, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007396
Ricardo Galhardoni
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Valquíria Aparecida da Silva
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Luís García-Larrea
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Camila Dale
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Abrahão F. Baptista
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Luciana Mendonça Barbosa
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Luciana Mendes Bahia Menezes
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Silvia R.D.T. de Siqueira
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Fernanda Valério
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Jefferson Rosi Jr
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Antonia Lilian de Lima Rodrigues
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Diego Toledo Reis Mendes Fernandes
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Priscila Mara Lorencini Selingardi
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Marco Antônio Marcolin
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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Fábio Luís de Souza Duran
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Carla Rachel Ono
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Leandro Tavares Lucato
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Ana Mércia B. L. Fernandes
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Fábio E. F. da Silva
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Lin T. Yeng
From the Pain Center (L.M.B., L.M.B.M., R.D.T.d.S., F.V., J.R., M.J.T., D.C.d.A.), Instituto do Câncer do Estado de São Paulo; Pain Center (R.G.G., V.S., A.L.d.L.R., D.T.R.M.F., P.M.L.S., M.A.M., S.R.D.T.d.S., A.M.B.L.F., M.J.T., D.C.d.A.), LIM62 Neurosurgery LIM, Department of Neurology, Instituto de Ortopedia e Traumatologia (L.T.Y.), Division of Physical Medicine and Rehabilitation, and Laboratory of Psychiatric Neuroimaging (LIM-21) (F.L.d.S.D.), Department and Institute of Psychiatry, School of Medicine, University of São Paulo; Service of Interdisciplinary Neuromodulation (R.G.G., V.S., A.R.B., M.J.T., D.C.d.A.), Laboratory of Neuroscience (LIM27) and National Institute of Biomarkers in Neuropsychiatry, Department and Institute of Psychiatry, Neuroradiology Section (L.T.L., F.E.F.d.S.), Instituto de Radiologia, and Department of Radiology (C.R.O., C.A.B.), University of São Paulo School of Medicine; Center for Mathematics, Computation and Cognition (A.F.B.), Federal University of ABC, São Bernardo do Campo; School of Medicine (R.G.G.), University of City of São Paulo; Department of Anatomy (C.D.), Institute of Biomedical Sciences of University of São Paulo, Brazil; and Central Integration of Pain (NeuroPain) (L.G.-L.), Lyon Centre for Neurosciences, Inserm U1028, University Claude Bernard Lyon 1, and Hospices Civils de Lyon, France.
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André R. Brunoni
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Carlos A. Buchpiguel
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Manoel J. Teixeira
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Daniel Ciampi de Andrade
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Insular and anterior cingulate cortex deep stimulation for central neuropathic pain
Disassembling the percept of pain
Ricardo Galhardoni, Valquíria Aparecida da Silva, Luís García-Larrea, Camila Dale, Abrahão F. Baptista, Luciana Mendonça Barbosa, Luciana Mendes Bahia Menezes, Silvia R.D.T. de Siqueira, Fernanda Valério, Jefferson Rosi, Antonia Lilian de Lima Rodrigues, Diego Toledo Reis Mendes Fernandes, Priscila Mara Lorencini Selingardi, Marco Antônio Marcolin, Fábio Luís de Souza Duran, Carla Rachel Ono, Leandro Tavares Lucato, Ana Mércia B. L. Fernandes, Fábio E. F. da Silva, Lin T. Yeng, André R. Brunoni, Carlos A. Buchpiguel, Manoel J. Teixeira, Daniel Ciampi de Andrade
Neurology Apr 2019, 92 (18) e2165-e2175; DOI: 10.1212/WNL.0000000000007396

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Abstract

Objective To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study.

Methods Participants were randomly allocated into the active PSI-rTMS, ACC-rTMS, sham-PSI-rTMS, or sham-ACC-rTMS arms. Stimulations were performed for 12 weeks, and a comprehensive clinical and pain assessment, psychophysics, and cortical excitability measurements were performed at baseline and during treatment. The main outcome of the study was pain intensity (numeric rating scale [NRS]) after the last stimulation session.

Results Ninety-eight patients (age 55.02 ± 12.13 years) completed the study. NRS score was not significantly different between groups at the end of the study. Active rTMS treatments had no significant effects on pain interference with daily activities, pain dimensions, neuropathic pain symptoms, mood, medication use, cortical excitability measurements, or quality of life. Heat pain threshold was significantly increased after treatment in the PSI-dTMS group from baseline (1.58, 95% confidence interval [CI] 0.09–3.06]) compared to sham-dTMS (−1.02, 95% CI −2.10 to 0.04, p = 0.014), and ACC-dTMS caused a significant decrease in anxiety scores (−2.96, 95% CI −4.1 to −1.7]) compared to sham-dTMS (−0.78, 95% CI −1.9 to 0.3; p = 0.018).

Conclusions ACC- and PSI-dTMS were not different from sham-dTMS for pain relief in CNP despite a significant antinociceptive effect after insular stimulation and anxiolytic effects of ACC-dTMS. These results showed that the different dimensions of pain can be modulated in humans noninvasively by directly stimulating deeper SNC cortical structures without necessarily affecting clinical pain per se.

ClinicalTrials.gov identifier: NCT01932905.

Glossary

ACC=
anterior cingulate cortex;
CE=
cortical excitability;
CI=
confidence interval;
CNP=
central neuropathic pain;
CPSP=
central poststroke pain;
dTMS=
deep transcranial magnetic stimulation;
NPSI=
Neuropathic Pain Symptoms Inventory;
NRS=
numeric rating scale;
PSI=
posterior superior insula;
QST=
quantitative sensory testing;
RMT=
rest motor threshold;
rTMS=
repetitive transcranial magnetic stimulation;
SCI=
spinal cord injury;
TA=
tibialis anterior

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received September 25, 2018.
  • Accepted in final form January 14, 2019.
  • © 2019 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain
    • Daniel Ciampi de Andrade, MD, University of São Paulo
    • Ricardo Galhardoni, DDS, PhD, University of São Paulo
    • Valquíria Aparecida da Silva, RN, University of São Paulo
    • Luís García-Larrea, MD, PhD, Inserm, University Claude Bernard Lyon 1, Hospices Civils de Lyon, France
    • Camila Dale, PhD, University of São Paulo
    • Abrahão F. Baptista, BPhysio, PhD, Federal University of ABC, São Bernardo do Campo
    • Luciana Mendonça Barbosa, MD, University of São Paulo
    • Luciana Mendes Bahia Menezes, MD, University of São Paulo
    • Silvia R.D.T. de Siqueira, PhD, DDS, Instituto do Câncer do Estado de São Paulo
    • Fernanda Valério, MD, Instituto do Câncer do Estado de São Paulo
    • Jefferson Rosi, MD, Instituto do Câncer do Estado de São Paulo
    • Antonia Lilian de Lima Rodrigues, RN, University of São Paulo
    • Diego Toledo Reis Mendes Fernandes, MD, University of São Paulo
    • Priscila Mara Lorencini Selingardi, MSc, University of São Paulo
    • Marco Antônio Marcolin, MD, PhD, University of São Paulo
    • Fábio Luís de Souza Duran, PhD, University of São Paulo
    • Carla Rachel Ono, MD, PhD, University of São Paulo School of Medicine
    • Leandro Tavares Lucato, MD, PhD, University of São Paulo School of Medicine
    • Ana Mércia B. L. Fernandes, BPhysio, University of São Paulo
    • Fábio E. F. da Silva, MD, University of São Paulo School of Medicine
    • Lin T. Yeng, MD, PhD, University of São Paulo
    • André R. Brunoni, MD, PhD, University of São Paulo School of Medicine
    • Carlos A. Buchpiguel, MD, PhD, University of São Paulo School of Medicine
    • Manoel J. Teixeira, MD, PhD, Instituto do Câncer do Estado de São Paulo, University of São Paulo
    Submitted June 28, 2019
  • Reader response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain
    • João Zugaib, Professor, Bahiana School of Medicine and Public Health
    • Janine R. Camatti, PhD Student, Federal University of ABC
    • Victor Hugo Souza, Postdoctoral Researcher, NBE, Aalto University School of Science (Finland)
    Submitted May 17, 2019
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