Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors
Chronic pain often predicts the onset of psychological distress. Symptoms including anxiety and depression after pain chronification reportedly are caused by brain remodeling/recruitment of the limbic and reward/aversion circuitries. Pain is the primary precipitating factor that has caused opioid ov...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | NeuroImage |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811920308296 |
| _version_ | 1818521494343385088 |
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| author | Sabrina L. McIlwrath Marena A. Montera Katherine M. Gott Yirong Yang Colin M. Wilson Reed Selwyn Karin N. Westlund |
| author_facet | Sabrina L. McIlwrath Marena A. Montera Katherine M. Gott Yirong Yang Colin M. Wilson Reed Selwyn Karin N. Westlund |
| author_sort | Sabrina L. McIlwrath |
| collection | DOAJ |
| description | Chronic pain often predicts the onset of psychological distress. Symptoms including anxiety and depression after pain chronification reportedly are caused by brain remodeling/recruitment of the limbic and reward/aversion circuitries. Pain is the primary precipitating factor that has caused opioid overprescribing and continued overuse of opioids leading to the current opioid epidemic. Yet experimental pain therapies often fail in clinical trials. Better understanding of underlying pathologies contributing to pain chronification is needed to address these chronic pain related issues. In the present study, a chronic neuropathic pain model persisting 10 weeks was studied. The model develops both anxiety- and pain-related behavioral measures to mimic clinical pain. The manganese-enhanced magnetic resonance imaging (MEMRI) utilized improved MRI signal contrast in brain regions with higher neuronal activity in the rodent chronic constriction trigeminal nerve injury (CCI-ION) model. T1-weighted MEMRI signal intensity was increased compared to controls in supraspinal regions of the anxiety and aversion circuitry, including anterior cingulate gyrus (ACC), amygdala, habenula, caudate, ventrolateral and dorsomedial periaqueductal gray (PAG). Despite continuing mechanical hypersensitivity, MEMRI T1 signal intensity as the neuronal activity measure, was not significantly different in thalamus and decreased in somatosensory cortex (S1BF) of CCI-ION rats compared to naïve controls. This is consistent with decreased fMRI BOLD signal intensity in thalamus and cortex of patients with longstanding trigeminal neuropathic pain reportedly associated with gray matter volume decrease in these regions. Significant increase in MEMRI T2 signal intensity in thalamus of CCI-ION animals was indication of tissue water content, cell dysfunction and/or reactive astrogliosis. Decreased T2 signal intensity in S1BF cortex of rats with CCI-ION was similar to findings of reduced T2 signals in clinical patients with chronic orofacial pain indicating prolonged astrocyte activation. These findings support use of MEMRI and chronic rodent models for preclinical studies and therapeutic trials to reveal brain sites activated only after neuropathic pain has persisted in timeframes relevant to clinical pain and to observe treatment effects not possible in short-term models which do not have evidence of anxiety-like behaviors. Potential improvement is predicted in the success rate of preclinical drug trials in future studies with this model. |
| first_indexed | 2024-12-11T01:51:48Z |
| format | Article |
| id | doaj.art-d185cf759c4e4b15b6f68d9b00831e6e |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-11T01:51:48Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-d185cf759c4e4b15b6f68d9b00831e6e2022-12-22T01:24:44ZengElsevierNeuroImage1095-95722020-12-01223117343Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviorsSabrina L. McIlwrath0Marena A. Montera1Katherine M. Gott2Yirong Yang3Colin M. Wilson4Reed Selwyn5Karin N. Westlund6Research Services New Mexico VA HealthCare System Albuquerque NM 87108 USA; Corresponding author.University of New Mexico Health Sciences Center, Albuquerque, NM USAUniversity of New Mexico Health Sciences Center, Albuquerque, NM USAUniversity of New Mexico Health Sciences Center, Albuquerque, NM USAUniversity of New Mexico Health Sciences Center, Albuquerque, NM USAUniversity of New Mexico Health Sciences Center, Albuquerque, NM USAResearch Services New Mexico VA HealthCare System Albuquerque NM 87108 USA; University of New Mexico Health Sciences Center, Albuquerque, NM USAChronic pain often predicts the onset of psychological distress. Symptoms including anxiety and depression after pain chronification reportedly are caused by brain remodeling/recruitment of the limbic and reward/aversion circuitries. Pain is the primary precipitating factor that has caused opioid overprescribing and continued overuse of opioids leading to the current opioid epidemic. Yet experimental pain therapies often fail in clinical trials. Better understanding of underlying pathologies contributing to pain chronification is needed to address these chronic pain related issues. In the present study, a chronic neuropathic pain model persisting 10 weeks was studied. The model develops both anxiety- and pain-related behavioral measures to mimic clinical pain. The manganese-enhanced magnetic resonance imaging (MEMRI) utilized improved MRI signal contrast in brain regions with higher neuronal activity in the rodent chronic constriction trigeminal nerve injury (CCI-ION) model. T1-weighted MEMRI signal intensity was increased compared to controls in supraspinal regions of the anxiety and aversion circuitry, including anterior cingulate gyrus (ACC), amygdala, habenula, caudate, ventrolateral and dorsomedial periaqueductal gray (PAG). Despite continuing mechanical hypersensitivity, MEMRI T1 signal intensity as the neuronal activity measure, was not significantly different in thalamus and decreased in somatosensory cortex (S1BF) of CCI-ION rats compared to naïve controls. This is consistent with decreased fMRI BOLD signal intensity in thalamus and cortex of patients with longstanding trigeminal neuropathic pain reportedly associated with gray matter volume decrease in these regions. Significant increase in MEMRI T2 signal intensity in thalamus of CCI-ION animals was indication of tissue water content, cell dysfunction and/or reactive astrogliosis. Decreased T2 signal intensity in S1BF cortex of rats with CCI-ION was similar to findings of reduced T2 signals in clinical patients with chronic orofacial pain indicating prolonged astrocyte activation. These findings support use of MEMRI and chronic rodent models for preclinical studies and therapeutic trials to reveal brain sites activated only after neuropathic pain has persisted in timeframes relevant to clinical pain and to observe treatment effects not possible in short-term models which do not have evidence of anxiety-like behaviors. Potential improvement is predicted in the success rate of preclinical drug trials in future studies with this model.http://www.sciencedirect.com/science/article/pii/S1053811920308296Magnetic resonance imagingNeuropathic painChronic painTrigeminal nerveOrofacial painCCI-ION |
| spellingShingle | Sabrina L. McIlwrath Marena A. Montera Katherine M. Gott Yirong Yang Colin M. Wilson Reed Selwyn Karin N. Westlund Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors NeuroImage Magnetic resonance imaging Neuropathic pain Chronic pain Trigeminal nerve Orofacial pain CCI-ION |
| title | Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors |
| title_full | Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors |
| title_fullStr | Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors |
| title_full_unstemmed | Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors |
| title_short | Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors |
| title_sort | manganese enhanced mri reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain and anxiety like behaviors |
| topic | Magnetic resonance imaging Neuropathic pain Chronic pain Trigeminal nerve Orofacial pain CCI-ION |
| url | http://www.sciencedirect.com/science/article/pii/S1053811920308296 |
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