PEDRO HENRIQUE MARTINS DA CUNHA
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- Non-invasive insular stimulation for peripheral neuropathic pain: Influence of target or symptom?(2022) CUNHA, Pedro Henrique Martins da; Liu Dongyang; FERNANDES, Ana Mercia; THIBES, Raissa Benocci; SATO, Joao; TANAKA, Harki; DALE, Camila; LAPA, Jorge Dornellys da Silva; MORAIS, Adriano Donizeth Silva de; SOARES, Felipe Henriques Carvalho; SILVA, Valquiria Aparecida da; GRAVEN-NIELSEN, Thomas; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deObjectives: The posterior-superior insula (PSI) has been shown to be a safe and potentially effective target for neuromodulation in peripheral neuropathic pain (PNP) in humans and animal models. However, it remains unknown whether there is a measurable responder profile to PSI stimulation. Two factors were hypothesized to influence the response of repetitive transcranial magnetic stimulation (rTMS) of the PSI: differences in rTMS target (discrete subregions of the PSI) or PNP phenotype. Methods: This is a secondary analysis from a randomized, double-blind, sham-controlled, crossover trial assessing PSI-rTMS in PNP (N = 31, 5 days rTMS) (10.1016/j.neucli.2021.06.003). Active PSI-rTMS true responders (>50% pain reduction from baseline after active but not after sham series of treatment) were compared with not true responders, to determine whether they differed with respect to 1) rTMS neuro-navigational target coordinates, and/or 2) specific neuropathic pain symptom inventory (NPSI) clusters (pinpointed pain, evoked pain, and deep pain) at baseline. Results: Mean rTMS target coordinates did not differ between true (n = 45.1%) and not true responders (p = 0.436 for X, p = 0.120 for Y, and p = 0.116 for Z). The Euclidian distance between true and not true responders was 4.04 mm. When comparing differences in responders between NPSI clusters, no participant within the evoked pain cluster was a true responder (p = 0.024). Conclusion: Response to PSI-rTMS may depend on pain cluster subtype rather than on differences in targeting within the PSI.
- The fast-posterior superior insula (Fast-PSI): A neuronavigation-free targeting method for non-invasive neuromodulation(2022) CUNHA, Pedro Henrique Martins da; TANAKA, Harki; LAPA, Jorge Dornellys da Silva; Liu Dongyang; SORTE JUNIOR, Anselmo Alves Boa; PEREIRA, Tamara Maria Ribeiro; SOARES, Felipe Henriques Carvalho; FERNANDES, Ana Mercia; SILVA, Valquiria Aparecida da; GRAVEN-NIELSEN, Thomas; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi de
- 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.
- Prevalence and characteristics of new-onset pain in COVID-19 survivours, a controlled study(2021) SOARES, Felipe Henriques Carvalho; KUBOTA, Gabriel Taricani; FERNANDES, Ana Mercia; HOJO, Bruno; COURAS, Catarina; COSTA, Barbara Venturoti; LAPA, Jorge Dornellys da Silva; BRAGA, Luiza Mansur; ALMEIDA, Matheus Merula de; CUNHA, Pedro Henrique Martins da; PEREIRA, Vitor Hugo Honorato; MORAIS, Adriano Donizeth Silva de; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deBackground We assessed whether COVID-19 is associated with de novo pain and de novo chronic pain (CP). Methods This controlled cross-sectional study was based on phone interviews of patients discharged from hospital after COVID-19 compared to the control group composed of individuals hospitalized during the same period due to non-COVID-19 causes. Patients were classified as having previous CP based on the ICD-11/IASP criteria, de novo pain (i.e. any new type of pain, irrespective of the pain status before hospital stay), and de novo CP (i.e. persistent or recurring de novo pain, lasting more than 3 months) after COVID-19. We assessed pain prevalence and its characteristics, including headache profile, pain location, intensity, interference, and its relationship with fatigue, and persistent anosmia. Forty-six COVID-19 and 73 control patients were included. Both groups had similar sociodemographic characteristics and past medical history. Results Length of in-hospital-stay and ICU admission rates were significantly higher amongst COVID-19 survivours, while mechanical ventilation requirement was similar between groups. Pre-hospitalisation pain was lower in COVID-19 compared to control group (10.9% vs. 42.5%; p = 0.001). However, the COVID-19 group had a significantly higher prevalence of de novo pain (65.2% vs. 11.0%, p = 0.001), as well as more de novo headache (39.1%) compared to controls (2.7%, p = 0.001). New-onset CP was 19.6% in COVID-19 patients and 1.4% (p = 0.002) in controls. These differences remained significant (p = 0.001) even after analysing exclusively (COVID: n = 40; controls: n = 34) patients who did not report previous pain before the hospital stay. No statistically significant differences were found for mean new-onset pain intensity and interference with daily activities between both groups. COVID-19 pain was more frequently located in the head/neck and lower limbs (p < 0.05). New-onset fatigue was more common in COVID-19 survivours necessitating inpatient hospital care (66.8%) compared to controls (2.5%, p = 0.001). COVID-19 patients who reported anosmia had more new-onset pain (83.3%) compared to those who did not (48.0%, p = 0.024). Conclusion COVID-19 was associated with a significantly higher prevalence of de novo CP, chronic daily headache, and new-onset pain in general, which was associated with persistent anosmia. Significance There exists de novo pain in a substantial number of COVID-19 survivours, and some develop chronic pain. New-onset pain after the infection was more common in patients who reported anosmia after hospital discharge.
- Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation(2023) KUBOTA, Gabriel T.; SOARES, Felipe H. C.; FONSECA, Alessandra S. da; ROSA, Talita dos Santos; SILVA, Valquiria A. da; GOUVEIA, Gisele R.; FARIA, Viviane G.; CUNHA, Pedro H. M. da; BRUNONI, Andre R.; TEIXEIRA, Manoel J.; ANDRADE, Daniel C. deBackgroundNew-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. MethodsA prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. ResultsThe present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. ConclusionsPost-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SignificanceCOVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.
- Burst Transspinal Magnetic Stimulation Alleviates Nociceptive Pain in Parkinson Disease-A Pilot Phase II Double-Blind, Randomized Study(2023) LAPA, Jorge Dornellys da Silva; CUNHA, Pedro Henrique Martins da; TEIXEIRA, Manoel Jacobsen; MEDEIROS, Vitor Macedo Brito; FERNANDES, Ana Mercia; MORAIS, Adriano Donizeth Silva de; GRAVEN-NIELSEN, Thomas; CURY, Rubens Gisbert; ANDRADE, Daniel Ciampi deBackground and Aims: Nociception is the most prevalent pain mechanism in Parkinson disease (PD). It negatively affects quality of life, and there is currently no evidence-based treatment for its control. Burst spinal cord stimulation has been used to control neuropathic pain and recently has been shown to relieve pain of nociceptive origin. In this study, we hypothesize that burst transspinal magnetic stimulation (bTsMS) reduces nociceptive pain in PD.Materials and Methods: Twenty-six patients were included in a double-blind, sham-controlled, randomized parallel trial design, and the analgesic effect of lower-cervical bTsMS was assessed in patients with nociceptive pain in PD. Five daily induction sessions were followed by maintenance sessions delivered twice a week for seven weeks. The primary outcome was the number of responders (& GE; 50% reduction of average pain intensity assessed on a numerical rating scale ranging from 0-10) during the eight weeks of treatment. Mood, quality of life, global impression of change, and adverse events were assessed throughout the study.Results: Twenty-six patients (46.2% women) were included in the study. The number of responders during treatment was significantly higher after active than after sham bTsMS (p = 0.044), mainly owing to the effect of the first week of treatment, when eight patients (61.5%) responded to active and two (15.4%) responded to sham bTsMS (p = 0.006); the number needed to treat was 2.2 at week 1. Depression symptom scores were lower after active (4.0 & PLUSMN; 3.1) than after sham bTsMS (8.7 & PLUSMN; 5.3) (p = 0.011). Patients' global impressions of change were improved after active bTsMS (70.0%) compared with sham bTsMS (18.2%; p = 0.030). Minor adverse events were reported in both arms throughout treatment sessions. One major side effect unrelated to treatment occurred in the active arm (death due to pulmonary embolism). Blinding was effective.Conclusion: BTsMS provided significant pain relief and improved the global impression of change in PD in this phase-II trial. Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT04546529.