ArticleJournal of neuroinflammation2015
The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of success and refractoriness in neuropathic pain?
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Motor cortex stimulation: a systematic literature-based analysis of effectiveness and case series experience.BMC neurology · 2019Pooled it
- The endocannabinoid system in the brain undergoes long-lasting changes following neuropathic pain.iScience · 2024Review
- Therapeutic potential of EVs loaded with CB2 receptor agonist in spinal cord injury via the Nrf2/HO-1 pathway.Redox report : communications in free radical research · 2024Article
- Article
- Neurocircuitry basis of motor cortex-related analgesia as an emerging approach for chronic pain management.Nature. Mental health · 2024Article
- Brain stimulation for chronic pain management: a narrative review of analgesic mechanisms and clinical evidence.Neurosurgical review · 2023Review
- Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain.International journal of molecular sciences · 2023Article
- Exercise facilitates regeneration after severe nerve transection and further modulates neural plasticity.Brain, behavior, & immunity - health · 2022Article
- Inhibition of Monoacylglycerol Lipase by NSD1819 as an Effective Strategy for the Endocannabinoid System Modulation against Neuroinflammation-Related Disorders.International journal of molecular sciences · 2022Article
- Cortical stimulation for chronic pain: from anecdote to evidence.European journal of physical and rehabilitation medicine · 2022Review
- Efficacy of a vegetal mixture composed ofFrontiers in nutrition · 2022Article
- Neuroimmune Interactions in Pain and Stress: An Interdisciplinary Approach.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2021Review
- Astroglial changes in the zona incerta in response to motor cortex stimulation in a rat model of chronic neuropathy.Scientific reports · 2020Article
- Bupivacaine effectively relieves inflammation-induced pain by suppressing activation of the NF-κB signalling pathway and inhibiting the activation of spinal microglia and astrocytes.Experimental and therapeutic medicine · 2017Article
- Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway.Journal of neurophysiology · 2017Article
- Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMotor cortex stimulation (MCS) is an effective treatment in neuropathic pain refractory to pharmacological management. However, analgesia is not satisfactorily obtained in one third of patients. Given the importance of understanding the mechanisms to overcome therapeutic limitations, we addressed the question: what mechanisms can explain both MCS effectiveness and refractoriness? Considering the crucial role of spinal neuroimmune activation in neuropathic pain pathophysiology, we hypothesized that modulation of spinal astrocyte and microglia activity is one of the mechanisms of action of MCS.
methodsRats with peripheral neuropathy (chronic nerve injury model) underwent MCS and were evaluated with a nociceptive test. Following the test, these animals were divided into two groups: MCS-responsive and MCS-refractory. We also evaluated a group of neuropathic rats not stimulated and a group of sham-operated rats. Some assays included rats with peripheral neuropathy that were treated with AM251 (a cannabinoid antagonist/inverse agonist) or saline before MCS. Finally, we performed immunohistochemical analyses of glial cells (microglia and astrocytes), cytokines (TNF-α and IL-1β), cannabinoid type 2 (CB2), μ-opioid (MOR), and purinergic P2X4 receptors in the dorsal horn of the spinal cord (DHSC).
findingsMCS reversed mechanical hyperalgesia, inhibited astrocyte and microglial activity, decreased proinflammatory cytokine staining, enhanced CB2 staining, and downregulated P2X4 receptors in the DHSC ipsilateral to sciatic injury. Spinal MOR staining was also inhibited upon MCS. Pre-treatment with AM251 blocked the effects of MCS, including the inhibitory mechanism on cells. Finally, MCS-refractory animals showed similar CB2, but higher P2X4 and MOR staining intensity in the DHSC in comparison to MCS-responsive rats.
conclusionsThese results indicate that MCS induces analgesia through a spinal anti-neuroinflammatory effect and the activation of the cannabinoid and opioid systems via descending inhibitory pathways. As a possible explanation for MCS refractoriness, we propose that CB2 activation is compromised, leading to cannabinoid resistance and consequently to the perpetuation of neuroinflammation and opioid inefficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.