Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain

Ricardo Galhardoni¹, Valquíria Aparecida da Silva¹, Luís García-Larrea¹, Camila Dale¹, Abrahão F Baptista¹, Luciana Mendonça Barbosa¹, Luciana Mendes Bahia Menezes¹, Silvia R D T de Siqueira¹, Fernanda Valério¹, Jefferson Rosi Jr¹, Antonia Lilian de Lima Rodrigues¹, Diego Toledo Reis Mendes Fernandes¹, Priscila Mara Lorencini Selingardi¹, Marco Antônio Marcolin¹, Fábio Luís de Souza Duran¹, Carla Rachel Ono¹, Leandro Tavares Lucato¹, Ana Mércia B L Fernandes¹, Fábio E F da Silva¹, Lin T Yeng¹, André R Brunoni¹, Carlos A Buchpiguel¹, Manoel J Teixeira¹, Daniel Ciampi de Andrade²

Affiliations

¹ 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.
² 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. ciampi@usp.br.

PMID: 30952795
DOI: 10.1212/WNL.0000000000007396

Randomized Controlled Trial

Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain

Ricardo Galhardoni et al. Neurology. 2019.

. 2019 Apr 30;92(18):e2165-e2175.

doi: 10.1212/WNL.0000000000007396. Epub 2019 Apr 5.

Authors

Affiliations

¹ 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.
² 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. ciampi@usp.br.

PMID: 30952795
DOI: 10.1212/WNL.0000000000007396

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.

Clinicaltrialsgov identifier: NCT01932905.

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Reader response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain.
Zugaib J, Camatti JR, Souza VH. Zugaib J, et al. Neurology. 2020 Apr 21;94(16):720-721. doi: 10.1212/WNL.0000000000009303. Neurology. 2020. PMID: 32312879 No abstract available.
Author response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain.
Ciampi de Andrade D, Galhardoni R, da Silva VA, García-Larrea L, Dale C, Baptista AF, Barbosa LM, Bahia Menezes LM, de Siqueira SRDT, Valério F, Rosi J, Lilian de Lima Rodrigues A, Toledo Reis Mendes Fernandes D, Selingardi PML, Marcolin MA, Luís de Souza Duran F, Ono CR, Lucato LT, Fernandes AMBL, da Silva FEF, Yeng LT, Brunoni AR, Buchpiguel CA, Teixeira MJ. Ciampi de Andrade D, et al. Neurology. 2020 Apr 21;94(16):721-722. doi: 10.1212/WNL.0000000000009304. Neurology. 2020. PMID: 32312880 No abstract available.

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Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain

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Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain

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