Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain — A pilot double-blind, randomized cross-over study

Dongyang, Liu; Fernandes, Ana Mércia; Cunha, Pedro Henrique Martins da; Tibes, Raissa; Sato, João Ricardo; Listik, Clarice; Dale, Camila S.; Kubota, Gabriel Taricani; Galhardoni, Ricardo; Teixeira, Manoel Jacobsen; Silva, Valquíria Aparecida da; Rosí, Jefferson; Andrade, Daniel Ciampi de

doi:10.1016/j.neucli.2021.06.003

Cited by 29 publications

(23 citation statements)

References 43 publications

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“…Similarly, using a conditioned pain modulation paradigm to study descending pain modulation in healthy subjects, it was shown that weaker pain inhibition is related to increased connectivity between the insula and amygdala [ 118 ]. Interestingly, insular transcranial magnetic stimulation in neuropathic patients is analgesic [ 82 ]. Similar results have recently been described in rodent models [ 119 , 120 ].…”

Section: Discussionmentioning

confidence: 99%

“…In central neuropathic pain patients, repeated TMS of the posterior insula increased thermal threshold without, however, affecting neuropathic pain scores [ 81 ]. On the contrary, in a study from the same group involving peripheral neuropathic pain patients, repeated TMS had a significant analgesic effect, which, however, was short-lasting [ 82 ]. In a pilot study in epileptic patients, electrical stimulation of the anterior insula increased heat pain thresholds [ 83 ].…”

Section: Association Of the Insular Cortex Function And Pain In Human...mentioning

confidence: 99%

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The Role of the Insular Cortex in Pain

Labrakakis

2023

IJMS

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The transition from normal to chronic pain is believed to involve alterations in several brain areas that participate in the perception of pain. These plastic changes are then responsible for aberrant pain perception and comorbidities. The insular cortex is consistently found activated in pain studies of normal and chronic pain patients. Functional changes in the insula contribute to chronic pain; however, the complex mechanisms by which the insula is involved in pain perception under normal and pathological conditions are still not clear. In this review, an overview of the insular function is provided and findings on its role in pain from human studies are summarized. Recent progress on the role of the insula in pain from preclinical experimental models is reviewed, and the connectivity of the insula with other brain regions is examined to shed new light on the neuronal mechanisms of the insular cortex’s contribution to normal and pathological pain sensation. This review underlines the need for further studies on the mechanisms underlying the involvement of the insula in the chronicity of pain and the expression of comorbid disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Association Of the Insular Cortex Function And Pain In Human...mentioning

confidence: 99%

The Role of the Insular Cortex in Pain

Labrakakis

2023

IJMS

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“…Using this approach, Lenoir et al (2018) reported a decrease in thermo‐nociceptive perception in healthy volunteers when applying deep rTMS to the posterior insula via continuous theta‐burst, and similar changes in heat pain thresholds (‘anti‐allodynic’ effects) were obtained in patients with central neuropathic pain receiving 10 Hz insular rTMS (Galhardoni et al, 2019). However, while there is emerging consensus that insular stimulation can change the perception of external stimuli, its effect on clinical ongoing pain remains equivocal: no clinical improvement was found in central neuropathic pain patients receiving deep insular rTMS (Galhardoni et al, 2019), while in a subsequent study patients with peripheral neuropathic pain showed analgesic responses to the same mode of stimulation (Dongyang et al, 2021). Although these data need replication, they tend to underscore again that different subsets of patients may be responsive to different types of intervention.…”

Section: Stimulating Extra‐motor Targetsmentioning

confidence: 99%

“…This strategy showed, for example, that patients responding positively to botulinum toxin clustered into specific sensory phenotypes and not in others (Bouhassira et al, 2021). This same strategy was recently applied to patients receiving rTMS to the posterior insula and disclosed that none of the responders to the intervention had a sensory phenotype characterized by predominant allodynic symptoms (Dongyang et al, 2021; Cunha & de Andrade 2022). Despite the obvious limitations of such post hoc analyses, the results suggest that selecting specific clinical presentations based on symptom profiles may increase the efficacy of rTMS at the individual level.…”

Section: Could It Be Simpler Than It Seems?—a Look At Patient's Symptomsmentioning

confidence: 99%

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Ciampi de Andrade,

García‐Larrea

2023

European Journal of Pain

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Background and ObjectiveRepetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex provides supplementary relief for some individuals with chronic pain who are refractory to pharmacological treatment. As rTMS slowly enters treatment guidelines for pain relief, its starts to be confronted with challenges long known to pharmacological approaches: efficacy at the group‐level does not grant pain relief for a particular patient. In this review, we present and discuss a series of ongoing attempts to overcome this therapeutic challenge in a personalized medicine framework.Databases and Data TreatmentRelevant scientific publications published in main databases such as PubMed and EMBASE from inception until March 2023 were systematically assessed, as well as a wide number of studies dedicated to the exploration of the mechanistic grounds of rTMS analgesic effects in humans, primates and rodents.ResultsThe main strategies reported to personalize cortical neuromodulation are: (i) the use of rTMS to predict individual response to implanted motor cortex stimulation; (ii) modifications of motor cortex stimulation patterns; (iii) stimulation of extra‐motor targets; (iv) assessment of individual cortical networks and rhythms to personalize treatment; (v) deep sensory phenotyping; (vi) personalization of location, precision and intensity of motor rTMS. All approaches except (i) have so far low or moderate levels of evidence.ConclusionsAlthough current evidence for most strategies under study remains at best moderate, the multiple mechanisms set up by cortical stimulation are an advantage over single‐target ‘clean’ drugs, as they can influence multiple pathophysiologic paths and offer multiple possibilities of individualization.SignificanceNon‐invasive neuromodulation is on the verge of personalised medicine. Strategies ranging from integration of detailed clinical phenotyping into treatment design to advanced patient neurophysiological characterisation are being actively explored and creating a framework for actual individualisation of care.

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“…In human patients, its efficacy remains unsettled: one sham-controlled study involving n =17 patients with visceral pain was reported positive 20 , but has not been replicated. In neuropathic pain, one ramdomised control trial on n =33 patients with central pain failed to demonstrate clinical effect 82 while another on n =31 subjects with peripheral neuropathic pain, studied by the same group, was positive 83 . Despite its inherent relevance as a target and the need of further controlled studies, the multimodal nature of the insula makes this region more susceptible than M1 to adverse effects from stimulation.…”

Section: Transcranial Magnetic Repetitive Stimulationmentioning

confidence: 99%

Non-invasive cortical stimulation for drug-resistant pain

García-Larrea

2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review Neuromodulation techniques are being increasingly used to alleviate pain and enhance quality of life. Non-invasive cortical stimulation was originally intended to predict the efficacy of invasive (neurosurgical) techniques, but has now gained a place as an analgesic procedure in its own right. Recent findings Repetitive transcranial magnetic stimulation (rTMS): Evidence from 14 randomised, placebo-controlled trials (~750 patients) supports a significant analgesic effect of high-frequency motor cortex rTMS in neuropathic pain. Dorsolateral frontal stimulation has not proven efficacious so far. The posterior operculo-insular cortex is an attractive target but evidence remains insufficient. Short-term efficacy can be achieved with NNT (numbers needed to treat) ~2–3, but long-lasting efficacy remains a challenge. Like rTMS, transcranial direct-current stimulation (tDCS) induces activity changes in distributed brain networks and can influence various aspects of pain. Lower cost relative to rTMS, few safety issues and availability of home-based protocols are practical advantages. The limited quality of many published reports lowers the level of evidence, which will remain uncertain until more prospective controlled studies are available. Summary Both rTMS and tDCS act preferentially upon abnormal hyperexcitable states of pain, rather than acute or experimental pain. For both techniques, M1 appears to be the best target for chronic pain relief, and repeated sessions over relatively long periods of time may be required to obtain clinically significant benefits. Patients responsive to tDCS may differ from those improved by rTMS.

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Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain — A pilot double-blind, randomized cross-over study

Cited by 29 publications

References 43 publications

The Role of the Insular Cortex in Pain

The Role of the Insular Cortex in Pain

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Non-invasive cortical stimulation for drug-resistant pain

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