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The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition
Neuropathic pain is a chronic disabling condition with a 7–10% of prevalence in the general population that is largely undertreated. Available analgesic therapies are poorly effective and are often accompanied by numerous side effects. Growing evidence indicates cannabinoids are a valuable treatment...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295062/ https://www.ncbi.nlm.nih.gov/pubmed/37371642 http://dx.doi.org/10.3390/biomedicines11061546 |
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author | Borgonetti, Vittoria Mugnaini, Claudia Corelli, Federico Galeotti, Nicoletta |
author_facet | Borgonetti, Vittoria Mugnaini, Claudia Corelli, Federico Galeotti, Nicoletta |
author_sort | Borgonetti, Vittoria |
collection | PubMed |
description | Neuropathic pain is a chronic disabling condition with a 7–10% of prevalence in the general population that is largely undertreated. Available analgesic therapies are poorly effective and are often accompanied by numerous side effects. Growing evidence indicates cannabinoids are a valuable treatment opportunity for neuropathic pain. The endocannabinoid system is an important regulator of pain perception through the CB1 receptors, but CB1 agonists, while largely effective, are not always satisfactory pain-relieving agents in clinics because of their serious adverse effects. Recently, several CB2 agonists have shown analgesic, anti-hyperalgesic, and anti-allodynic activity in the absence of CB1-induced psychostimulant effects, offering promise in neuropathic pain management. The aim of this study was to evaluate the anti-neuropathic activity of a novel selective CB2 agonist, COR167, in a preclinical model of peripheral neuropathy, the spared nerve injury (SNI). Oral COR167, in a dose-dependent manner, attenuated mechanical allodynia and thermal hyperalgesia after acute and repeated administration, showing the absence of tolerance induction. At anti-neuropathic doses, COR167 did not show any alteration in the locomotor behavior. SNI mice showed increased microglial levels of HDAC1 protein in the ipsilateral side of the spinal cord, along with NF-kB activation. COR167 treatment prevented the HDAC1 overexpression and the NF-kB activation and increased the levels of the anti-inflammatory cytokine IL-10 through a CB2-mediated mechanism. Oral administration of COR167 shows promising therapeutic potential in the management of neuropathic pain conditions. |
format | Online Article Text |
id | pubmed-10295062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102950622023-06-28 The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition Borgonetti, Vittoria Mugnaini, Claudia Corelli, Federico Galeotti, Nicoletta Biomedicines Article Neuropathic pain is a chronic disabling condition with a 7–10% of prevalence in the general population that is largely undertreated. Available analgesic therapies are poorly effective and are often accompanied by numerous side effects. Growing evidence indicates cannabinoids are a valuable treatment opportunity for neuropathic pain. The endocannabinoid system is an important regulator of pain perception through the CB1 receptors, but CB1 agonists, while largely effective, are not always satisfactory pain-relieving agents in clinics because of their serious adverse effects. Recently, several CB2 agonists have shown analgesic, anti-hyperalgesic, and anti-allodynic activity in the absence of CB1-induced psychostimulant effects, offering promise in neuropathic pain management. The aim of this study was to evaluate the anti-neuropathic activity of a novel selective CB2 agonist, COR167, in a preclinical model of peripheral neuropathy, the spared nerve injury (SNI). Oral COR167, in a dose-dependent manner, attenuated mechanical allodynia and thermal hyperalgesia after acute and repeated administration, showing the absence of tolerance induction. At anti-neuropathic doses, COR167 did not show any alteration in the locomotor behavior. SNI mice showed increased microglial levels of HDAC1 protein in the ipsilateral side of the spinal cord, along with NF-kB activation. COR167 treatment prevented the HDAC1 overexpression and the NF-kB activation and increased the levels of the anti-inflammatory cytokine IL-10 through a CB2-mediated mechanism. Oral administration of COR167 shows promising therapeutic potential in the management of neuropathic pain conditions. MDPI 2023-05-26 /pmc/articles/PMC10295062/ /pubmed/37371642 http://dx.doi.org/10.3390/biomedicines11061546 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Borgonetti, Vittoria Mugnaini, Claudia Corelli, Federico Galeotti, Nicoletta The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title | The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title_full | The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title_fullStr | The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title_full_unstemmed | The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title_short | The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition |
title_sort | selective cb2 agonist cor167 reduced symptoms in a mice model of trauma-induced peripheral neuropathy through hdac-1 inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295062/ https://www.ncbi.nlm.nih.gov/pubmed/37371642 http://dx.doi.org/10.3390/biomedicines11061546 |
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