Spinal intracellular metabotropic glutamate receptor 5 (mGluR5) contributes to pain and c-fos expression in a rat model of inflammatory pain
| Autor: | André Laferrière, Shu Fan Wang, Terence J. Coderre, Naresh Kumar, Kathleen Vincent |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Proto-Oncogene Proteins c-jun Microdialysis Receptor Metabotropic Glutamate 5 Freund's Adjuvant Intracellular Space Glutamic Acid Pain Histone Deacetylase 1 Biology Pharmacology 03 medical and health sciences 0302 clinical medicine Spinal Cord Dorsal Horn mental disorders Animals Rats Long-Evans Inflammation Cyclodextrins Metabotropic glutamate receptor 5 Metabotropic glutamate receptor 4 Metabotropic glutamate receptor 7 Glutamate receptor Metabotropic glutamate receptor 6 Cadherins Rats Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine Spinal Cord nervous system Neurology Metabotropic glutamate receptor Conditioning Operant Metabotropic glutamate receptor 1 Neurology (clinical) Excitatory Amino Acid Transporter 4 Proto-Oncogene Proteins c-fos Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Pain. 158:705-716 |
| ISSN: | 1872-6623 0304-3959 |
| DOI: | 10.1097/j.pain.0000000000000823 |
| Popis: | Metabotropic glutamate receptor 5 (mGluR5) is an excitatory G-protein-coupled receptor (GPCR) present in the spinal cord dorsal horn (SCDH) where it has a well-established role in pain. In addition to its traditional location on the cytoplasmic membrane, recent evidence shows that these receptors are present intracellularly on the nuclear membrane in the spinal cord dorsal horn and are implicated in neuropathic pain. Nuclear mGluR5 is a functional receptor that binds glutamate entering the cell through the neuronal glutamate transporter (GT) EAAT3 and activates transcription factor c-fos, whereas plasma membrane mGluR5 is responsible for c-jun activation. Here, we extend these findings to a model of inflammatory pain using complete Freund's adjuvant (CFA) and show that nuclear mGluR5 is also upregulated in the spinal cord dorsal horn following inflammation. We also show that pretreatment with an excitatory amino acid transporter (EAAT) inhibitor attenuates pain and decreases Fos, but not Jun, expression in complete Freund's adjuvant rats. In contrast, selective glial glutamate transporter inhibitors are pronociceptive and increase spinal glutamate concentrations. Additionally, we found that permeable mGluR5 antagonists are more effective at attenuating pain and Fos expression than nonpermeable group I mGluR antagonists. Taken together, these results suggest that under inflammatory conditions, intracellular mGluR5 is actively involved in the relay of nociceptive information in the spinal cord. |
| Databáze: | OpenAIRE |
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