Repetitive motor cortex stimulation reinforces the pain modulation circuits of peripheral neuropathic pain

Cha, Min‐Ji; Um, Sun Woo; Kwon, Minjee; Nam, Taick Sang

doi:10.1038/s41598-017-08208-2

Cited by 31 publications

(20 citation statements)

References 49 publications

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“…Repetitive TMS [49] and fMRI [50] studies documented that patients suffering from chronic pain presented with altered spinocortical and intracortical excitability of primary motor cortex, that could contribute to the impairment of their motor performance and the limited modulation of chronic symptoms related to the pain condition [51]. Recent studies [52] on animal models, confirmed that the repetitive stimulation of motor cortex is able to modify synaptic connections involved in pain control, with an adjustment of mechanical hypersensitivity occurring in neuropathic pain. Activation of the motor cortex has an analgesic effect on pain conditions [53], but the motor cortical dysfunction that seemed to characterize FM patients could reduce the modulating effect on pain.…”

Section: Reduced Motor Performance and Motor Cortical Areas Activatiomentioning

confidence: 99%

Mutual interaction between motor cortex activation and pain in fibromyalgia: EEG-fNIRS study

et al. 2020

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Background Experimental and clinical studies suggested an analgesic effect on chronic pain by motor cortex activation. The present study explored the complex mechanisms of interaction between motor and pain during performing the slow and fast finger tapping task alone and in concomitant with nociceptive laser stimulation. Method The participants were 38 patients with fibromyalgia (FM) and 21 healthy subjects. We used a simultaneous multimodal method of laser-evoked potentials and functional near-infrared spectroscopy to investigate metabolic and electrical changes during the finger tapping task and concomitant noxious laser stimulation. Functional near-infrared spectroscopy is a portable and optical method to detect cortical metabolic changes. Laser-evoked potentials are a suitable tool to study the nociceptive pathways function. Results We found a reduced tone of cortical motor areas in patients with FM compared to controls, especially during the fast finger tapping task. FM patients presented a slow motor performance in all the experimental conditions, requesting rapid movements. The amplitude of laser evoked potentials was different between patients and controls, in each experimental condition, as patients showed smaller evoked responses compared to controls. Concurrent phasic pain stimulation had a low effect on motor cortex metabolism in both groups nor motor activity changed laser evoked responses in a relevant way. There were no correlations between Functional Near-Infrared Spectroscopy (FNIRS) and clinical features in FM patients.

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Section: Reduced Motor Performance and Motor Cortical Areas Activatiomentioning

confidence: 99%

Mutual interaction between motor cortex activation and pain in fibromyalgia: EEG-fNIRS study

et al. 2020

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“…no. 38450; Ugo Basile, Gemonio, Italy) [ 15 ]. Briefly, rats were placed individually in plexiglass boxes equipped with a wire mesh floor to acclimate to the testing environment for 10 min, or enough time to cease exploratory behavior.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of differentially expressed microRNAs and mRNAs in dorsal root ganglia from streptozotocin-induced diabetic rats

et al. 2018

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Diabetic peripheral neuropathy is a common complication associated with diabetes mellitus with a pathogenesis that is incompletely understood. By regulating RNA silencing and post-transcriptional gene expression, microRNAs participate in various biological processes and human diseases. However, the relationship between microRNAs and the progress of diabetic peripheral neuropathy still lacks a thorough exploration. Here we used microarray microRNA and mRNA expression profiling to analyze the microRNAs and mRNAs which are aberrantly expressed in dorsal root ganglia from streptozotocin-induced diabetic rats. We found that 37 microRNAs and 1357 mRNAs were differentially expressed in comparison to non-diabetic samples. Bioinformatics analysis indicated that 399 gene ontology terms and 29 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in diabetic rats. Additionally, a microRNA-gene network evaluation identified rno-miR-330-5p, rno-miR-17-1-3p and rno-miR-346 as important players for network regulation. Finally, quantitative real-time polymerase chain reaction analysis was used to confirm the microarray results. In conclusion, this study provides a systematic perspective of microRNA and mRNA expression in dorsal root ganglia from diabetic rats, and suggests that dysregulated microRNAs and mRNAs may be important promotors of peripheral neuropathy. Our results may be the underlying framework of future studies regarding the effect of the aberrantly expressed genes on the pathophysiology of diabetic peripheral neuropathy.

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“…A hole was made in the skull overlying the M1, and custom-made insulated bipolar platinum electrodes (height, 70 μm; exposed tip, 50 μm; distance between electrodes, 500 μm) were applied epidurally above the M1 at stereotaxic coordinates determined from previous MCS experiments (anterior, 1.8 mm; lateral, 2 mm), contralateral to the nerve injury site (Fig. 1A) 61 . The stimulation electrodes for MCS were held in place with two bone screws and dental cement.…”

Section: Stimulation Electrode Implantationmentioning

confidence: 99%

Astroglial changes in the zona incerta in response to motor cortex stimulation in a rat model of chronic neuropathy

Cha

Lee

2020

Sci Rep

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Although astrocytes are known to regulate synaptic transmission and affect new memory formation by influencing long-term potentiation and functional synaptic plasticity, their role in pain modulation is poorly understood. Motor cortex stimulation (MCS) has been used to reduce neuropathic pain through the incertothalamic pathway, including the primary motor cortex (M1) and the zona incerta (ZI). However, there has been no in-depth study of these modulatory effects and region-specific changes in neural plasticity. In this study, we investigated the effects of MCS-induced pain modulation as well as the relationship between the ZI neuroplasticity and MCS-induced pain alleviation in neuropathic pain (NP). MCS-induced threshold changes were evaluated after daily MCS. Then, the morphological changes of glial cells were compared by tissue staining. In order to quantify the neuroplasticity, MAP2, PSD95, and synapsin in the ZI and M1 were measured and analyzed with western blot. In behavioral test, repetitive MCS reduced NP in nerve-injured rats. We also observed recovered GFAP expression in the NP with MCS rats. In the NP with sham MCS rats, increased CD68 level was observed. In the NP with MCS group, increased mGluR1 expression was observed. Analysis of synaptogenesis-related molecules in the M1 and ZI revealed that synaptic changes occured in the M1, and increased astrocytes in the ZI were more closely associated with pain alleviation after MCS. Our findings suggest that MCS may modulate the astrocyte activities in the ZI and synaptic changes in the M1. Our results may provide new insight into the important and numerous roles of astrocytes in the formation and function. Chronic neuropathic pain (NP) is the result of primary lesion in peripheral nerve and/or central nervous system (CNS) dysfunction in the absence of nociceptor stimulation 1. This multidimensional clinical entity is mediated by various pathophysiological mechanisms, making its treatment difficult 2,3. Neuropathic pain refractory to medication has been treated with invasive methods, such as selective lesioning and electrical stimulation of the central or peripheral nervous system 4. MCS was initially applied to central pain secondary to thalamic stroke 5,6. Over time, its usage expanded to various types of chronic pain. Repetitive MCS relieves approximately 45 to 75% of pain 7,8 , making it a viable option for patients with severe drug-refractory symptoms. Motor cortex stimulation (MCS) treatment was first used in the early 1990s to treat a patient with chronic, drug-resistant NP 9. Despite the clinical use of MCS for pain reduction, the mechanisms underlying its effects remain unclear. The incertothalamic pathway was recently described as a novel system for regulating nociceptive processing in the thalamus 10,11. In this pathway, the zona incerta (ZI) inhibits the flow of nociceptive and somatosensory information in the posterior thalamus (Po), and this is mediated by the cholinergic system 10,12. Modulation of the ZI activity by repeated MCS was shown to...

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Repetitive motor cortex stimulation reinforces the pain modulation circuits of peripheral neuropathic pain

Cited by 31 publications

References 49 publications

Mutual interaction between motor cortex activation and pain in fibromyalgia: EEG-fNIRS study

Mutual interaction between motor cortex activation and pain in fibromyalgia: EEG-fNIRS study

Comprehensive analysis of differentially expressed microRNAs and mRNAs in dorsal root ganglia from streptozotocin-induced diabetic rats

Astroglial changes in the zona incerta in response to motor cortex stimulation in a rat model of chronic neuropathy

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