Investigation of spinal nerve ligation-mediated functional activation of the rat brain using manganese-enhanced MRI

Jeong, Keun‐Yeong; Kang, Ji-Hyuk

doi:10.1538/expanim.17-0033

Cited by 11 publications

(18 citation statements)

References 26 publications

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Section: Discussionmentioning

confidence: 99%

“…Since MEMRI studies were used to demonstrate the identifying pain pathways in the brain, various pain imaging studies have been performed in the spinal cord and brain [6,7]. Nerve injury [10] and thermal [11] stimulus-induced abnormal brain activities have been shown using MEMRI. In addition, our previous formalin-induced pain study also showed that MEMRI could be a good indicator of pain-induced changes in the CNS [7].…”

Section: Introductionmentioning

confidence: 99%

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Manganese-enhanced MRI depicts a reduction in brain response to nociception by mTOR inhibition in chronic pain rats

Cha

Choi

Kim

et al. 2020

Preprint

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Neuropathic pain induced by a nerve injury could lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in the chronic pain model were difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed the cerebrocortical excitability changes and compared the regional Mn 2+ enhancement after mTOR inhibitions. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1 and XL388) effects were compared within groups using MEMRI. In the results, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region (S1HL), motor cortex 1/2 (M1/2), and anterior cingulate cortex (ACC) regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, the rostral-caudal analysis of the IC indicated that the rostral region of the IC was more associated with pain perception than caudal region. Our data suggest that MEMRI could present the pain-related signal changes in the brain, and mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Manganese-enhanced MRI depicts a reduction in brain response to nociception by mTOR inhibition in chronic pain rats

Cha

Choi

Kim

et al. 2020

Preprint

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“…Until now, the effects of mTOR inhibitor using animal MRI have not been studied. Several studies have used the MEMRI method to assess pain in the central nervous system or to observe changes in pain through analgesic use [3,10,24]. However, the MEMRI method has several di culties in observing the effects of pain reduction or changes in neuronal activities.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental hyperalgesia produces the up-regulated neuronal activation of brain responses within pain-processing regions, including the anterior cingulate cortex (ACC), insular cortex (IC), and primary (SI) and secondary somatosensory cortices (SII) [7][8][9]. With MEMRI studies having been found useful in identifying pain pathways in the brain, various pain imaging studies have been performed in the spinal cord and brain [5,6], allowing researchers to visualize nerve injury [10] and thermal [11] stimulus-induced abnormal brain activities. Similarly, our previous formalininduced pain study also showed that MEMRI could be a good indicator of pain-induced changes in the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

Manganese-enhanced MRI depicts a reduction in brain response to nociception upon mTOR inhibition in chronic pain rats

Cha

Choi

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn 2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

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“…Thus, the contralateral RSgA in the SNI model seems an important hub, which integrates the nociceptive information and works directly with numerous painrelated structures in a segregated network. Other studies have demonstrated an increase of the cerebral blood flow, BOLD, and manganese-enhanced signals within the retrosplenial cortex in different pain models, 10,26 suggesting that RSgA activation is conserved through different types of chronic pain. Moreover, aberrant DMN functioning in chronic pain patients has been reported with the functional connectivity between the PFC and the retrosplenial cortex (posterior cingulate) correlated with pain rumination, underlying their involvement in the emotional aspect of pain.…”

Section: The Retrosplenial Cortex As a Pain Integrator Structurementioning

confidence: 94%

Structural and functional alterations in the retrosplenial cortex following neuropathic pain

Barrière

Hamieh

Magalhães

et al. 2019

Pain

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Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions. In this article, we conducted a longitudinal and multimodal study to assess how chronic pain affects the brain. Using the spared nerve injury model which promotes both long-lasting mechanical and thermal allodynia/hyperalgesia but also painassociated comorbidities, we showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 1 and 2 months after injury. We found that both functional metrics and connectivity of the part A of the retrosplenial granular cortex (RSgA) were significantly correlated with the development of neuropathic pain behaviours. In addition, we found that the functional RSgA connectivity to the subiculum and the prelimbic system are significantly increased in spared nerve injury animals and correlated with peripheral pain thresholds. These brain regions were previously linked to the development of comorbidities associated with neuropathic pain. Using a voxel-based morphometry approach, we showed that neuropathic pain induced a significant increase of the gray matter concentration within the RSgA, associated with a significant activation of both astrocytes and microglial cells. Together, functional and morphological imaging metrics of the RSgA could be used as a predictive biomarker of neuropathic pain.

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Investigation of spinal nerve ligation-mediated functional activation of the rat brain using manganese-enhanced MRI

Cited by 11 publications

References 26 publications

Manganese-enhanced MRI depicts a reduction in brain response to nociception by mTOR inhibition in chronic pain rats

Manganese-enhanced MRI depicts a reduction in brain response to nociception by mTOR inhibition in chronic pain rats

Manganese-enhanced MRI depicts a reduction in brain response to nociception upon mTOR inhibition in chronic pain rats

Structural and functional alterations in the retrosplenial cortex following neuropathic pain

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