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Sci Rep. 2017 Aug 29;7(1):9743. doi: 10.1038/s41598-017-09991-8.

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

Chung G1,2, Kim CY1,3, Yun YC1, Yoon SH1,3, Kim MH1,3, Kim YK4, Kim SJ5,6,7,8.

Author information

1
Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
2
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
4
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
5
Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. sangjkim@snu.ac.kr.
6
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea. sangjkim@snu.ac.kr.
7
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. sangjkim@snu.ac.kr.
8
Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea. sangjkim@snu.ac.kr.

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.

PMID:
28851991
PMCID:
PMC5575341
DOI:
10.1038/s41598-017-09991-8
[Indexed for MEDLINE]
Free PMC Article

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