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TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhanc...

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Autores principales: Sintsova, Oksana, Gladkikh, Irina, Klimovich, Anna, Palikova, Yulia, Palikov, Viktor, Styshova, Olga, Monastyrnaya, Margarita, Dyachenko, Igor, Kozlov, Sergey, Leychenko, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301426/
https://www.ncbi.nlm.nih.gov/pubmed/34201624
http://dx.doi.org/10.3390/biomedicines9070716
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author Sintsova, Oksana
Gladkikh, Irina
Klimovich, Anna
Palikova, Yulia
Palikov, Viktor
Styshova, Olga
Monastyrnaya, Margarita
Dyachenko, Igor
Kozlov, Sergey
Leychenko, Elena
author_facet Sintsova, Oksana
Gladkikh, Irina
Klimovich, Anna
Palikova, Yulia
Palikov, Viktor
Styshova, Olga
Monastyrnaya, Margarita
Dyachenko, Igor
Kozlov, Sergey
Leychenko, Elena
author_sort Sintsova, Oksana
collection PubMed
description Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.
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spelling pubmed-83014262021-07-24 TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation Sintsova, Oksana Gladkikh, Irina Klimovich, Anna Palikova, Yulia Palikov, Viktor Styshova, Olga Monastyrnaya, Margarita Dyachenko, Igor Kozlov, Sergey Leychenko, Elena Biomedicines Communication Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular. MDPI 2021-06-23 /pmc/articles/PMC8301426/ /pubmed/34201624 http://dx.doi.org/10.3390/biomedicines9070716 Text en © 2021 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 Communication
Sintsova, Oksana
Gladkikh, Irina
Klimovich, Anna
Palikova, Yulia
Palikov, Viktor
Styshova, Olga
Monastyrnaya, Margarita
Dyachenko, Igor
Kozlov, Sergey
Leychenko, Elena
TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title_full TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title_fullStr TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title_full_unstemmed TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title_short TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation
title_sort trpv1 blocker hcrg21 suppresses tnf-α production and prevents the development of edema and hypersensitivity in carrageenan-induced acute local inflammation
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301426/
https://www.ncbi.nlm.nih.gov/pubmed/34201624
http://dx.doi.org/10.3390/biomedicines9070716
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