Epidural Posterior Insular Stimulation Alleviates Neuropathic Pain Manifestations in Rats With Spared Nerve Injury Through Endogenous Opioid System

Komboz, Fares; Mehsein, Zeinab; Kobaïter-Maarrawi, Sandra; Chehade, Hiba-Douja; Maarrawi, Joseph

doi:10.1016/j.neurom.2022.01.002

Cited by 4 publications

(5 citation statements)

References 53 publications

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“…The integration and processing of nociceptive inputs in the brain involve multiple cortical areas beyond sensory‐motor and prefrontal cortices (Garcia‐Larrea & Bastuji, 2018; Kucyi & Davis, 2017; Peyron et al, 2019). Structures of the so‐called ‘nociceptive matrix’ such as the parietal operculum and posterior insula are the target of most spinothalamic projections reaching the primate cortex (Dum et al, 2009; Garcia‐Larrea & Peyron, 2013), and experimental studies in animals have reported that epidural or deep brain stimulation of insular areas analogous to the human posterior insula led to analgesia, which needed opioid, cannabinoid and/or GABA receptors availability to occur (Alonso‐Matielo et al, 2021; Chehade et al, 2021; Dimov et al, 2018; Franca et al, 2013; Komboz et al, 2022). In humans, direct electric stimulation of the posterior superior insula at ‘inhibitory’ high frequencies (150 Hz) increased heat pain thresholds in patients undergoing stereo‐EEG for focal epilepsy surgery (Denis et al, 2016).…”

Section: Stimulating Extra‐motor Targetsmentioning

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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Section: Stimulating Extra‐motor Targetsmentioning

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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“…Although studies have not yet extended ICS to the human insula, one preclinical study in rodents suggests a potential role for low frequency intracortical pI stimulation in relief from chronic neuropathic pain. Importantly for this review, all forms of analgesia examined in this study were blocked by naloxone, clearly implicating endogenous opioid release ( Komboz et al, 2022 ). Although opioid peptides and receptors are prominent in pI, it remains to be determined whether local opioid signaling, activation of afferents from other structures, or projections to the DPMS are involved.…”

Section: Future Outlookmentioning

confidence: 86%

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

Lubejko

Graham

Livrizzi

et al. 2022

Front. Syst. Neurosci.

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Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.

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“…On the other hand, the present study did not evaluate receptor activation or expression, what in fact may stand for differences after nerve injury and ESI. Glial cells are crucial for the development and maintenance of neuropathic pain 17,40 . Activated glia sustains neuronal functions, regulates synapses, and facilitates nociceptive neurotransmission, while participating in the sensitization of neurons located in the dorsal horn of the spinal cord 17,40 .…”

Section: Discussionmentioning

confidence: 99%

“…Glial cells are crucial for the development and maintenance of neuropathic pain 17,40 . Activated glia sustains neuronal functions, regulates synapses, and facilitates nociceptive neurotransmission, while participating in the sensitization of neurons located in the dorsal horn of the spinal cord 17,40 . Activation of astrocytes in dorsal horn has been described after CCI 15,41 and has been suggested to play a role in the genesis of allodinia 42 .…”

Section: Discussionmentioning

confidence: 99%

Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cord

Gonçalves,

Matielo,

Teixeira

et al. 2022

BRJP

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BACKGROUND AND OBJECTIVES: Half of neuropathic pain patients still end up failing clinical treatments. Electrical stimulation of the posterior insular cortex (ESI) modulates sensory and nociceptive circuits. This study evaluated the effects of a range of frequencies of ESI proposed to improve neuropathic pain. METHODS: Male Sprague Dawley rats, 280-340 g, submitted to the chronic constriction of the right sciatic nerve were tested for mechanical sensitivity using the paw pressure and von Frey filaments tests, and for thermal sensitivity using the hot plate test. The rats were submitted to ESI 10, 60 or 100 Hz (one, five or seven ESI, 15 min, 210 µs, 1V), applied to the posterior insular cortex, and were evaluated in the tests before and after ESI, or in follow-up of 48, 72 and 168h. The open field evaluated general activity after ESI 5. The involvment of opioid and cannabinoid testes were evaluated through treatment with naloxone and SR1416A -antagonist Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cordA estimulação elétrica do córtex insular posterior induz antinocicepção opioide e canabinoide dependente e regula células da glia na medula espinal

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Epidural Posterior Insular Stimulation Alleviates Neuropathic Pain Manifestations in Rats With Spared Nerve Injury Through Endogenous Opioid System

Cited by 4 publications

References 53 publications

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

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

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cord

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