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Investigating the inhibitory effect of glutamate subunit 8 metabotropic receptor stimulation in the periaqueductal gray area in the central neuropathic pain model
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Marjan Hosseini   , Mohsen Parviz , Alireza P. Shabanzadeh , Elham Zamani , Parvaneh Mohseni-Moghaddam , Leila Gholami , Shima Mehrabadi , Roham Mazloom |
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Abstract: (238 Views) |
Introduction: The pathophysiology of neuropathic pain is very complex. It involves several environmental and central mechanisms. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, in a model of chronic central neuropathic pain in male rats.
Methods and Materials: In this study, a total of 50 Wistar rats were used, which were randomly divided into 5 groups of 10; Three weeks after the induction of spinal cord injury (in order to induce central neuropathic pain, we used the spinal cord compression model in T6-T8 spinal cord cut), DCPG, siRNA and normal saline (solvent drugs) were injected into the periaqueductal gray area by stereotaxic surgery. Before the injection of drugs and 30 and 60 minutes after injection, Paw's withdrawal response to acetone (cold allodynia) was assessed through an acetone test. The brains of some animals were removed for immunohistochemical examination of the activity level of Off cells in the RVM region after transcardial perfusion, and several samples were also used for western blotting analysis of the expression level of mGluR8.
Results: Intracerebral administration (PAG) of metabotropic receptor agonist No. 8 increased the pain threshold of animals when exposed to the non-painful cold stimulus; In addition, immunohistochemical examination of Off cells in the RVM area showed that DCPG injection can increase the inhibitory activity of these cells. Also, there was a decrease in the expression of 8 mGluR in SCI and siRNA group animals and a relative increase in the expression of these receptors after treatment.
Conclusion: The results of this study showed that increasing the activity of mGluR8 in the periaqueductal gray area will be able to improve some central neuropathic pain symptoms (including cold allodynia) by modulating the activity of inhibitory cells in the RVM region to an acceptable extent. Finally, by observing the increased expression of mGluR8, we came to the conclusion that the activation of these receptors can have an inhibitory role on cell death caused by damage to the central nervous system.
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| Keywords: Metabotropic Glutamate Receptor 8, Central Neuropathic Pain, Spinal Cord Injury, Periaqueductal Gray Area |
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Full-Text [PDF 265 kb]
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Type of Study: Research |
Subject:
General
Received: 2024/01/23 | Accepted: 2023/08/1 | Published: 2023/08/1
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