Upregulation of prefrontal metabotropic glutamate receptor 5 mediates neuropathic pain and negative mood symptoms after spinal nerve injury in rats

Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor...

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Published inScientific reports Vol. 7; no. 1; pp. 9743 - 14
Main Authors Chung, Geehoon, Kim, Chae Young, Yun, Yeong-Chan, Yoon, Sang Ho, Kim, Myoung-Hwan, Kim, Yu Kyeong, Kim, Sang Jeong
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 29.08.2017
Nature Publishing Group
Subjects
631/378/1457/1945
631/378/1689/1414
631/378/1689/2610
692/699/375/1692
692/699/476/1414
Affect
Animals
Anxiety
Chronic pain
Comorbidity
Disease Models, Animal
Emotions
Glutamic acid receptors (metabotropic)
Humanities and Social Sciences
Hypersensitivity
Mental depression
Mood
multidisciplinary
Neuralgia
Neuralgia - physiopathology
Pain
Pain Perception
Positron emission tomography
Prefrontal cortex
Prefrontal Cortex - diagnostic imaging
Prefrontal Cortex - physiology
Radioactive tracers
Rats
Receptor, Metabotropic Glutamate 5 - biosynthesis
Rodents
Science
Science (multidisciplinary)
Spinal cord
Spinal Nerves
Up-Regulation
Wounds and Injuries
Online AccessGet full text

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Abstract Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats. Among the brain areas, a prominent upregulation of mGluR5 was shown in the prelimbic region (PrL) of the medial prefrontal cortex (mPFC) of chronic neuropathic pain animals. A pharmacological blockade of upregulated mGluR5 in the PrL ameliorated the negative symptoms including tactile hypersensitivity and depressive-like behavior, which relieved the subjects from the unpleasant state of chronic neuropathic pain condition. Conversely, lentiviral overexpression of the mGluR5 in the PrL of naïve rats successfully induced comorbid pain and negative moods. Our data provide deeper insight into the shared mechanism of pain perception and negative emotions, identifying a therapeutic target for the treatment of chronic pain and mood disorders.
AbstractList Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats. Among the brain areas, a prominent upregulation of mGluR5 was shown in the prelimbic region (PrL) of the medial prefrontal cortex (mPFC) of chronic neuropathic pain animals. A pharmacological blockade of upregulated mGluR5 in the PrL ameliorated the negative symptoms including tactile hypersensitivity and depressive-like behavior, which relieved the subjects from the unpleasant state of chronic neuropathic pain condition. Conversely, lentiviral overexpression of the mGluR5 in the PrL of naïve rats successfully induced comorbid pain and negative moods. Our data provide deeper insight into the shared mechanism of pain perception and negative emotions, identifying a therapeutic target for the treatment of chronic pain and mood disorders.
Abstract Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats. Among the brain areas, a prominent upregulation of mGluR5 was shown in the prelimbic region (PrL) of the medial prefrontal cortex (mPFC) of chronic neuropathic pain animals. A pharmacological blockade of upregulated mGluR5 in the PrL ameliorated the negative symptoms including tactile hypersensitivity and depressive-like behavior, which relieved the subjects from the unpleasant state of chronic neuropathic pain condition. Conversely, lentiviral overexpression of the mGluR5 in the PrL of naïve rats successfully induced comorbid pain and negative moods. Our data provide deeper insight into the shared mechanism of pain perception and negative emotions, identifying a therapeutic target for the treatment of chronic pain and mood disorders.
ArticleNumber 9743
Author Kim, Sang Jeong
Chung, Geehoon
Kim, Yu Kyeong
Yoon, Sang Ho
Kim, Myoung-Hwan
Kim, Chae Young
Yun, Yeong-Chan
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  organization: Department of Physiology, Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul National University College of Medicine
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  givenname: Yu Kyeong
  surname: Kim
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  organization: Department of Nuclear Medicine, Seoul National University College of Medicine
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  organization: Department of Physiology, Seoul National University College of Medicine, Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Department of Biomedical Sciences, Seoul National University College of Medicine, Neuroscience Research Institute, Seoul National University College of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28851991$$D View this record in MEDLINE/PubMed
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Snippet Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive...
Abstract Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the...
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SubjectTerms 631/378/1457/1945
631/378/1689/1414
631/378/1689/2610
692/699/375/1692
692/699/476/1414
Affect
Animals
Anxiety
Chronic pain
Comorbidity
Disease Models, Animal
Emotions
Glutamic acid receptors (metabotropic)
Humanities and Social Sciences
Hypersensitivity
Mental depression
Mood
multidisciplinary
Neuralgia
Neuralgia - physiopathology
Pain
Pain Perception
Positron emission tomography
Prefrontal cortex
Prefrontal Cortex - diagnostic imaging
Prefrontal Cortex - physiology
Radioactive tracers
Rats
Receptor, Metabotropic Glutamate 5 - biosynthesis
Rodents
Science
Science (multidisciplinary)
Spinal cord
Spinal Nerves
Up-Regulation
Wounds and Injuries
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Title Upregulation of prefrontal metabotropic glutamate receptor 5 mediates neuropathic pain and negative mood symptoms after spinal nerve injury in rats
URI https://link.springer.com/article/10.1038/s41598-017-09991-8
https://www.ncbi.nlm.nih.gov/pubmed/28851991
https://www.proquest.com/docview/1958290362
https://search.proquest.com/docview/1933944029
https://pubmed.ncbi.nlm.nih.gov/PMC5575341
Volume 7
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