Electrical stimulation of the posterior insula induces mechanical analgesia in a rodent model of neuropathic pain by modulating GABAergic signaling and activity in the pain circuitry

Matielo, Heloísa Alonso; Gonçalves, Elizamara S.; Campos, Mariana F. de; Oliveira, Victória R.S.; Toniolo, Elaine F.; Alves, A.S.; Lebrun, Ivo; Andrade, Daniel Ciampi de; Teixeira, Manoel Jacobsen; Britto, Luiz Roberto Giorgetti de; Hamani, Clement; Dale, Camila S.

doi:10.1016/j.brainres.2020.147237

Cited by 24 publications

(26 citation statements)

References 45 publications

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“…Using viral tracing, optogenetics, and whole-cell recording, we revealed that the IC Glu →BLA pathway was required for the sensory discriminative and aversive-affective components of pain. The multiple effects of the IC Glu →BLA pathway in pain processing are likely caused by different subregions of the IC because the posterior IC is preferentially involved in processing somatosensory features of pain, while the anterior IC preferentially mediates the affective component ( 39 , 40 , 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Meng

Yue

Liu

et al. 2022

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Meng

Yue

Liu

et al. 2022

Journal of Biological Chemistry

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“…Pain perception is affected by alterations in the cerebral pain network [ 33 ]; chronic neuropathic pain is caused by hyperexcitability. Studies have also identified an important role for central plasticity, given the long-term nature of chronic pain [ 3 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Scrambler Therapy for Chronic Pain after Burns and Its Effect on the Cerebral Pain Network: A Prospective, Double-Blinded, Randomized Controlled Trial

Lee

Park

Cho

et al. 2022

JCM

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Chronic pain is common after burn injuries, and post-burn neuropathic pain is the most important complication that is difficult to treat. Scrambler therapy (ST) is a non-invasive modality that uses patient-specific electrocutaneous nerve stimulation and is an effective treatment for many chronic pain disorders. This study used magnetic resonance imaging (MRI) to evaluate the pain network-related mechanisms that underlie the clinical effect of ST in patients with chronic burn-related pain. This prospective, double-blinded, randomized controlled trial (ClinicalTrials.gov: NCT03865693) enrolled 43 patients who were experiencing chronic neuropathic pain after unilateral burn injuries. The patients had moderate or greater chronic pain (a visual analogue scale (VAS) score of ≥5), despite treatment using gabapentin and other physical modalities, and were randomized 1:1 to receive real or sham ST sessions. The ST was performed using the MC5-A Calmare device for ten 45 min sessions (Monday to Friday for 2 weeks). Baseline and post-treatment parameters were evaluated subjectively using the VAS score for pain and the Hamilton Depression Rating Scale; MRI was performed to identify objective central nervous system changes by measuring the cerebral blood volume (CBV). After 10 ST sessions (two weeks), the treatment group exhibited a significant reduction in pain relative to the sham group. Furthermore, relative to the pre-ST findings, the post-ST MRI evaluations revealed significantly decreased CBV in the orbito-frontal gyrus, middle frontal gyrus, superior frontal gyrus, and gyrus rectus. In addition, the CBV was increased in the precentral gyrus and postcentral gyrus of the hemisphere associated with the burned limb in the ST group, as compared with the CBV of the sham group. Thus, a clinical effect from ST on burn pain was observed after 2 weeks, and a potential mechanism for the treatment effect was identified. These findings suggest that ST may be an alternative strategy for managing chronic pain in burn patients.

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“…However, high-frequency stimulation of the posterior insula raises patients' thermal pain thresholds [83]. Further, a recent study in rats has suggested that stimulation of the posterior insula provides pain alleviation by modulating GAB-Aergic signaling [84]. These findings indicate that the insula may be a potential target for pain neuromodulation by adjusting stimulation parameters and specific target locations.…”

Section: Network Connectivity Of Neuromodulation Targets For Pain Reliefmentioning

confidence: 99%

Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets

Yamamoto

Elias

Beyn

et al. 2021

Stereotact Funct Neurosurg

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Background: Chronic pain is a debilitating condition that imposes a tremendous burden on health-care systems around the world. While frontline treatments for chronic pain involve pharmacological and psychological approaches, neuromodulation can be considered for treatment-resistant cases. Neuromodulatory approaches for pain are diverse in both modality and target and their mechanism of action is incompletely understood. Objectives: The objectives of this study were to (i) understand the current landscape of pain neuromodulation research through a comprehensive survey of past and current registered clinical trials (ii) investigate the network underpinnings of these neuromodulatory treatments by performing a connectomic mapping analysis of cortical and subcortical brain targets that have been stimulated for pain relief. Methods: A search for clinical trials involving pain neuromodulation was conducted using 2 major trial databases (ClinicalTrials.gov and the International Clinical Trials Registry Platform). Trials were categorized by variables and analyzed to gain an overview of the contemporary research landscape. Additionally, a connectomic mapping analysis was performed to investigate the network connectivity patterns of analgesic brain stimulation targets using a normative connectome based on a functional magnetic resonance imaging dataset. Results: In total, 487 relevant clinical trials were identified. Noninvasive cortical stimulation and spinal cord stimulation trials represented 49.3 and 43.7% of this count, respectively, while deep brain stimulation trials accounted for <3%. The mapping analysis revealed that superficial target connectomics overlapped with deep target connectomics, suggesting a common pain network across the targets. Conclusions: Research for pain neuromodulation is a rapidly growing field. Our connectomic network analysis reinforced existing knowledge of the pain matrix, identifying both well-described hubs and more obscure structures. Further studies are needed to decode the circuits underlying pain relief and determine the most effective targets for neuromodulatory treatment.

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Electrical stimulation of the posterior insula induces mechanical analgesia in a rodent model of neuropathic pain by modulating GABAergic signaling and activity in the pain circuitry

Cited by 24 publications

References 45 publications

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Scrambler Therapy for Chronic Pain after Burns and Its Effect on the Cerebral Pain Network: A Prospective, Double-Blinded, Randomized Controlled Trial

Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets

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