JEFFERSON ROSI JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
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- Corticomotor excitability is altered in central neuropathic pain compared with non-neuropathic pain or pain-free patients(2023) BARBOSA, Luciana Mendonca; VALERIO, Fernanda; SILVA, Valquiria Aparecida da; RODRIGUES, Antonia Lilian de Lima; GALHARDONI, Ricardo; YENG, Lin Tchia; JUNIR, Jefferson Rosi; CONFORTO, Adriana Bastos; LUCATO, Leandro Tavares; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deObjectives: Central neuropathic pain (CNP) is associated with altered corticomotor excitability (CE), which can potentially provide insights into its mechanisms. The objective of this study is to describe the CE changes that are specifically related to CNP.Methods: We evaluated CNP associated with brain injury after stroke or spinal cord injury (SCI) due to neuromyelitis optica through a battery of CE measurements and comprehensive pain, neurological, functional, and quality of life assessments. CNP was compared to two groups of patients with the same disease: i. with non-neuropathic pain and ii. without chronic pain, matched by sex and lesion location.Results: We included 163 patients (stroke=93; SCI=70: 74 had CNP, 43 had non-neuropathic pain, and 46 were pain-free). Stroke patients with CNP had lower motor evoked potential (MEP) in both affected and unaffected hemispheres compared to non-neuropathic pain and no-pain patients. Patients with CNP had lower amplitudes of MEPs (366 mu V +/- 464 mu V) than non-neuro-pathic (478 +/- 489) and no-pain (765 mu V +/- 880 mu V) patients, p < 0.001. Short-interval intracorti-cal inhibition (SICI) was defective (less inhibited) in patients with CNP (2.6 +/- 11.6) compared to no-pain (0.80.7), p = 0.021. MEPs negatively correlated with mechanical and cold-induced allo-dynia. Furthermore, classifying patients' results according to normative data revealed that at least 75% of patients had abnormalities in some CE parameters and confirmed MEP findings based on group analyses.Discussion: CNP is associated with decreased MEPs and SICI compared to non-neuropathic pain and no-pain patients. Corticomotor excitability changes may be helpful as neurophysiological markers of the development and persistence of pain after CNS injury, as they are likely to pro-vide insights into global CE plasticity changes occurring after CNS lesions associated with CNP.(c) 2023 The Author(s).
- Insular and anterior cingulate cortex deep stimulation for central neuropathic pain Disassembling the percept of pain(2019) GALHARDONI, Ricardo Geront; SILVA, Valquiria Aparecida da; GARCIA-LARREA, Luis; DALE, Camila; BAPTISTA, Abrahao F.; BARBOSA, Luciana Mendonca; MENEZES, Luciana Mendes Bahia; SIQUEIRA, Silvia R. D. T. de; VALERIO, Fernanda; ROSI JR., Jefferson; RODRIGUES, Antonia Lilian de Lima; FERNANDES, Diego Toledo Reis Mendes; SELINGARDI, Priscila Mara Lorencini; MARCOLIN, Marco Antonio; DURAN, Fabio Luis de Souza; ONO, Carla Rachel; LUCATO, Leandro Tavares; FERNANDES, Ana Mercia B. L.; SILVA, Fabio E. F. da; YENG, Lin T.; BRUNONI, Andre R.; BUCHPIGUEL, Carlos A.; TEIXEIRA, Manoel J.; ANDRADE, Daniel Ciampi deObjective 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.
- Into the Island: A new technique of non-invasive cortical stimulation of the insula(2012) ANDRADE, D. Ciampi de; GALHARDONI, R.; PINTO, L. F.; LANCELOTTI, R.; ROSI JR., J.; MARCOLIN, M. A.; TEIXEIRA, M. J.Study aim. - We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. Introduction. - Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. Methods. - The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. Results. - Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. Conclusions. - The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients.
- Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain - A pilot double-blind, randomized cross-over study(2021) DONGYANG, Liu; FERNANDES, Ana Mercia; CUNHA, Pedro Henrique Martins da; TIBES, Raissa; SATO, Joao; LISTIK, Clarice; DALE, Camila; KUBOTA, Gabriel Taricani; GALHARDONI, Ricardo; TEIXEIRA, Manoel Jacobsen; SILVA, Valquiria Aparecida da; ROSI, Jefferson; ANDRADE, Daniel Ciampi deObjectives. - Peripheral neuropathic pain (pNeP) is prevalent, and current treatments, including drugs and motor cortex repetitive transcranial magnetic stimulation (rTMS) leave a substantial proportion of patients with suboptimal pain relief. Methods. - We explored the intensity and short-term duration of the analgesic effects produced in pNeP patients by 5 days of neuronavigated deep rTMS targeting the posterior superior insula (PSI) with a double-cone coil in a sham-controlled randomized cross-over trial. Results. - Thirty-one pNeP patients received induction series of five active or sham consecutive sessions of daily deep-rTMS to the PSI in a randomized sequence, with a washout period of at least 21 days between series. The primary outcome [number of responders (>50% pain intensity reduction from baseline in a numerical rating scale ranging from 0 to 10)] was significantly higher after real (58.1%) compared to sham (19.4%) stimulation (p = 0.002). The number needed to treat was 2.6, and the effect size was 0.97 [95% CI (0.6; 1.3)]. One week after the 5th stimulation day, pain scores were no longer different between groups, and no difference in neuropathic pain characteristics and interference with daily living were present. No major side effects occurred, and milder adverse events (i.e., short-lived headaches after stimulation) were reported in both groups. Blinding was effective, and analgesic effects were not affected by sequence of the stimulation series (active-first or sham-first), age, sex or pain duration of participants. Discussion. - PSI deep-rTMS was safe in refractory pNeP and was able to provide significant pain intensity reduction after a five-day induction series of treatments. Post-hoc assessment of neuronavigation targeting confirmed deep-rTMS was delivered within the boundaries of the PSI in all participants. Conclusion. - PSI deep-rTMS provided significant pain relief during 5-day induction sessions compared to sham stimulation.
- Author response: Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain(2020) ANDRADE, Daniel Ciampi de; GALHARDONI, Ricardo; SILVA, Valquiria Aparecida da; GARCIA-LARREA, Luis; DALE, Camila; BAPTISTA, Abrahao F.; BARBOSA, Luciana Mendonca; MENEZES, Luciana Mendes Bahia; SIQUEIRA, Silvia R. D. T. de; VALERIO, Fernanda; ROSI, Jefferson; RODRIGUES, Antonia Lilian de Lima; FERNANDES, Diego Toledo Reis Mendes; SELINGARDI, Priscila Mara Lorencini; MARCOLIN, Marco Antonio; DURAN, Fabio Luis de Souza; ONO, Carla Rachel; LUCATO, Leandro Tavares; FERNANDES, Ana Mercia B. L.; SILVA, Fabio E. F. da; YENG, Lin T.; BRUNONI, Andre R.; BUCHPIGUEL, Carlos A.; TEIXEIRA, Manoel J.
- Long-term deep-TMS does not negatively affect cognitive functions in stroke and spinal cord injury patients with central neuropathic pain(2019) SELINGARDI, Priscila Mara Lorencini; RODRIGUES, Antonia Lilian de Lima; SILVA, Valquiria Aparecida da; FERNANDES, Diego Toledo Reis Mendes; ROSI JR., Jefferson; MARCOLIN, Marco Antonio; YENG, Lin T.; BRUNONI, Andre R.; TEIXEIRA, Manoel J.; GALHARDONI, Ricardo; ANDRADE, Daniel Ciampi de
bookPart Dor Central Encefálica(2019) OLIVEIRA, Rogério Adas Ayres de; JR, Jefferson Rosi; GALHARDONI, Ricardo; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi Araujo de- Dissecting neuropathic from poststroke pain: the white matter within(2022) LEMOS, Marcelo Delboni; FAILLENOT, Isabelle; LUCATO, Leandro Tavares; TEIXEIRA, Manoel Jacobsen; BARBOSA, Luciana Mendonca; ALHO, Eduardo Joaquim Lopes; CONFORTO, Adriana Bastos; RODRIGUES, Antonia Lilian de Lima; GALHARDONI, Ricardo; SILVA, Valquiria Aparecida da; LISTIK, Clarice; ROSI, Jefferson; PEYRON, Roland; GARCIA-LARREA, Luis; ANDRADE, Daniel Ciampi dePoststroke pain (PSP) is a heterogeneous term encompassing both central neuropathic (ie, central poststroke pain [CPSP]) and nonneuropathic poststroke pain (CNNP) syndromes. Central poststroke pain is classically related to damage in the lateral brainstem, posterior thalamus, and parietoinsular areas, whereas the role of white matter connecting these structures is frequently ignored. In addition, the relationship between stroke topography and CNNP is not completely understood. In this study, we address these issues comparing stroke location in a CPSP group of 35 patients with 2 control groups: 27 patients with CNNP and 27 patients with stroke without pain. Brain MRI images were analyzed by 2 complementary approaches: an exploratory analysis using voxel-wise lesion symptom mapping, to detect significant voxels damaged in CPSP across the whole brain, and a hypothesis-driven, region of interest-based analysis, to replicate previously reported sites involved in CPSP. Odds ratio maps were also calculated to demonstrate the risk for CPSP in each damaged voxel. Our exploratory analysis showed that, besides known thalamic and parietoinsular areas, significant voxels carrying a high risk for CPSP were located in the white matter encompassing thalamoinsular connections (one-tailed threshold Z > 3.96, corrected P value <0.05, odds ratio = 39.7). These results show that the interruption of thalamocortical white matter connections is an important component of CPSP, which is in contrast with findings from nonneuropathic PSP and from strokes without pain. These data can aid in the selection of patients at risk to develop CPSP who could be candidates to pre-emptive or therapeutic interventions.
- Site matters: Central neuropathic pain characteristics and somatosensory findings after brain and spinal cord lesions(2023) BARBOSA, Luciana Mendonca; VALERIO, Fernanda da; PEREIRA, Samira Luisa Apostolos; SILVA, Valquiria Aparecida da; RODRIGUES, Antonia Lilian de Lima; GALHARDONI, Ricardo; YENG, Lin Tchia; JR, Jefferson Rosi; CONFORTO, Adriana Bastos; LUCATO, Leandro Tavares; LEMOS, Marcelo Delboni; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deBackground: It is unknown if different etiologies or lesion topographies influence central neuropathic pain (CNP) clinical manifestation.Methods: We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the central nervous system to gain insight into CNP mechanisms. We compared the CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain, central poststroke pain (CPSP, n = 39), and the spinal cord central pain due to spinal cord injury (CPSCI, n = 40) in neuromyelitis optica.Results: Results are expressed as median (25th to 75th percentiles). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI (p < 0.001), and lower cold thermal limen (5.6? [0.0-12.9]) compared to CPSCI (20.0? [4.2-22.9]; p = 0.004). CPSCI also had higher mechanical pain thresholds (784.5 mN [255.0-1078.0]) compared to CPSP (235.2 mN [81.4-1078.0], p = 0.006) and higher mechanical detection threshold compared to control areas (2.7 [1.5-6.2] vs. 1.0 [1.0-3.3], p = 0.007). Evoked pain scores negatively correlated with mechanical pain thresholds (r = -0.38, p < 0.001) and wind-up ratio (r = -0.57, p < 0.001).Conclusions: CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype mechanism correlations and impact trial designs for the main etiologies of CNP, namely stroke and spinal cord lesions. This study provides evidence that topography may influence pain symptoms and sensory profile. The findings suggest that CNP mechanisms might vary according to pain etiology or lesion topography, impacting future mechanism-based treatment choices.
- Dissecting central post-stroke pain: a controlled symptom-psychophysical characterization(2022) BARBOSA, Luciana Mendonca; SILVA, Valquiria Aparecida da; RODRIGUES, Antonia Lilian de Lima; FERNANDES, Diego Toledo Reis Mendes; OLIVEIRA, Rogerio Adas Ayres de; GALHARDONI, Ricardo; YENG, Lin Tchia; ROSI JUNIOR, Jefferson; CONFORTO, Adriana Bastos; LUCATO, Leandro Tavares; LEMOS, Marcelo Delboni; PEYRON, Roland; GARCIA-LARREA, Luis; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deDissection of distinct post-stroke pain syndromes evidenced that the neuropathic pain inventory, the presence of cold thermal deficit and the finding of allodynia on bedside examination, explained 77% of the occurrence of neuropathic central post-stroke pain, a new finding that has clear diagnostic potential. Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8-41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (rho = -0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (rho = -0.4; P = 0.008) and heat pain thresholds (rho = 0.5; P = 0.003), burning pain with mechanical detection (rho = -0.4; P = 0.015) and mechanical pain thresholds (rho = -0.4, P < 0.013), evoked pain with mechanical pain threshold (rho = -0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.