Antinociceptive Effects of the GPR55 Antagonist CID16020046 Injected into the Rat Anterior Cingulate Cortex
| Autor: | Brendan Harhen, Gemma Mc Laughlin, Bright N. Okine, Jessica C. Gaspar, David P. Finn, Michelle Roche |
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| Přispěvatelé: | Science Foundation Ireland, Conselho Nacionalde Desenvolvimento Cientifico e Tecnologico, Brazil |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty CID16020046 PROTEIN Pain Periaqueductal gray c-Fos Benzoates Gyrus Cinguli PERIAQUEDUCTAL GRAY Receptors G-Protein-Coupled ACTIVATION Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine FORMALIN TEST Internal medicine medicine Premovement neuronal activity Animals Receptors Cannabinoid Microinjection Anterior cingulate cortex prefrontal cortex Analgesics biology Chemistry General Neuroscience Antagonist NOCICEPTION LYSOPHOSPHATIDYLINOSITOL SENSITIZATION Rats AMYGDALA ERK 030104 developmental biology medicine.anatomical_structure Nociception Endocrinology nervous system biology.protein GPR55 Immediate early gene Azabicyclo Compounds 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 443 |
| ISSN: | 1873-7544 |
| Popis: | The G-protein coupled receptor, GPR55, modulates nociceptive processing. Given the expression of GPR55 in the anterior cingulate cortex (ACC), a key brain region involved in the cognitive and affective dimensions of pain, the present study tested the hypothesis that GPR55 signalling in the ACC facilitates inflammatory pain behaviour in rats. The expression of GPR55 in the ACC was confirmed by both western blotting and immunostaining, with evidence for neuronal localisation. Microinjection of the selective GPR55 antagonist CID16020046 into the ACC of adult male Sprague-Dawley rats significantly reduced second phase formalin-evoked nociceptive behaviour compared with vehicle-treated controls. CID16020046 administration was associated with a reduction in phosphorylation of extracellular signal-regulated kinase (ERK), a downstream target of GPR55 activation, in the ACC. Intra-ACC administration of CID16020046 prevented the formalin-induced increases in expression of mRNA coding for the immediate early gene and marker of neuronal activity, c-Fos, in the ipsilateral dorsal horn of the spinal cord. Intra-plantar injection of formalin reduced tissue levels of the endogenous GPR55 ligand 2-arachidonoyl-sn-glycero-3-phosphoinositol (2-AGPI) in the ACC, likely reflecting its increased release/utilisation. These data suggest that endogenous activation of GPR55 signalling and increased ERK phosphorylation in the ACC facilitates inflammatory pain via top-down modulation of descending pain control. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved. This work was funded by a research grant from Science Foundation Ireland (10/IN.1/B2976) and from Conselho Nacionalde Desenvolvimento Cientifico e Tecnologico, Brazil (CNPq; 207530/2014-9). peer-reviewed 2021-07-13 |
| Databáze: | OpenAIRE |
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