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Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats

BACKGROUND: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have sh...

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Autores principales: Mehrabadi, Shima, Karimiyan, Seyed Morteza, Ashabi, Ghorbangol, Moradbeygi, Khadijeh, Hoseini, Marjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pasteur Institute of Iran 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601548/
https://www.ncbi.nlm.nih.gov/pubmed/32660223
http://dx.doi.org/10.29252/ibj.24.6.374
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author Mehrabadi, Shima
Karimiyan, Seyed Morteza
Ashabi, Ghorbangol
Moradbeygi, Khadijeh
Hoseini, Marjan
author_facet Mehrabadi, Shima
Karimiyan, Seyed Morteza
Ashabi, Ghorbangol
Moradbeygi, Khadijeh
Hoseini, Marjan
author_sort Mehrabadi, Shima
collection PubMed
description BACKGROUND: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in TRPV-1 expression during administration of morphine have a pivotal role in developing morphine tolerance. Therefore, the effect of baclofen on TRPV-1 expression during chronic administration of morphine was investigated in this study. METHODS: A total of 48 rats were divided into four groups of control, morphine single injection, morphine tolerance, and morphine tolerance + baclofen. To induce morphine tolerance in rats, animals received 10 mg/kg of i.p. morphine sulfate once a day for 10 days. In the treatment group, baclofen (0.5 mg/kg) was injected for 10 days, before morphine injection. Finally, to evaluate baclofen treatment on morphine analgesia and hyperalgesia, thermal hyperalgesia and formalin test were used. TRPV-1 and PKC expression and protein production in DRG of spinal cord were then evaluated by real-time PCR and Western blot. RESULTS: In baclofen treatment group, thermal hyperalgesia and formalin test improved in comparison with morphine tolerance group. In morphine tolerance group, both TRPV-1/PKC gene expression and protein levels increased in comparison with the control group. However, following the baclofen treatment, the TRPV-1 and PKC levels decreased. CONCLUSION: Baclofen can enhance anti-nociceptive effect of morphine by modulating TRPV-1 channel and PKC activity.
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spelling pubmed-76015482020-11-13 Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats Mehrabadi, Shima Karimiyan, Seyed Morteza Ashabi, Ghorbangol Moradbeygi, Khadijeh Hoseini, Marjan Iran Biomed J Full Length BACKGROUND: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in TRPV-1 expression during administration of morphine have a pivotal role in developing morphine tolerance. Therefore, the effect of baclofen on TRPV-1 expression during chronic administration of morphine was investigated in this study. METHODS: A total of 48 rats were divided into four groups of control, morphine single injection, morphine tolerance, and morphine tolerance + baclofen. To induce morphine tolerance in rats, animals received 10 mg/kg of i.p. morphine sulfate once a day for 10 days. In the treatment group, baclofen (0.5 mg/kg) was injected for 10 days, before morphine injection. Finally, to evaluate baclofen treatment on morphine analgesia and hyperalgesia, thermal hyperalgesia and formalin test were used. TRPV-1 and PKC expression and protein production in DRG of spinal cord were then evaluated by real-time PCR and Western blot. RESULTS: In baclofen treatment group, thermal hyperalgesia and formalin test improved in comparison with morphine tolerance group. In morphine tolerance group, both TRPV-1/PKC gene expression and protein levels increased in comparison with the control group. However, following the baclofen treatment, the TRPV-1 and PKC levels decreased. CONCLUSION: Baclofen can enhance anti-nociceptive effect of morphine by modulating TRPV-1 channel and PKC activity. Pasteur Institute of Iran 2020-11 2020-06-21 /pmc/articles/PMC7601548/ /pubmed/32660223 http://dx.doi.org/10.29252/ibj.24.6.374 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Length
Mehrabadi, Shima
Karimiyan, Seyed Morteza
Ashabi, Ghorbangol
Moradbeygi, Khadijeh
Hoseini, Marjan
Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title_full Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title_fullStr Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title_full_unstemmed Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title_short Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats
title_sort repeated administration of baclofen modulates trpv-1 channel expression by pkc pathway in dorsal root ganglia of spinal cord in a morphine tolerance model of rats
topic Full Length
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601548/
https://www.ncbi.nlm.nih.gov/pubmed/32660223
http://dx.doi.org/10.29252/ibj.24.6.374
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