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Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats

PURPOSE: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca(2+))-channel protein...

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Autores principales: Xu, Songchao, Yi, Yusheng, Wang, Yanting, Wang, Pei, Zhao, Yang, Feng, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397435/
https://www.ncbi.nlm.nih.gov/pubmed/36016537
http://dx.doi.org/10.2147/JPR.S378893
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author Xu, Songchao
Yi, Yusheng
Wang, Yanting
Wang, Pei
Zhao, Yang
Feng, Wei
author_facet Xu, Songchao
Yi, Yusheng
Wang, Yanting
Wang, Pei
Zhao, Yang
Feng, Wei
author_sort Xu, Songchao
collection PubMed
description PURPOSE: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca(2+))-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α2) adrenoreceptor agonist that mediates intracellular Ca(2+) levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG). METHODS: The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. RESULTS: Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors. CONCLUSION: The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG.
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spelling pubmed-93974352022-08-24 Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats Xu, Songchao Yi, Yusheng Wang, Yanting Wang, Pei Zhao, Yang Feng, Wei J Pain Res Original Research PURPOSE: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca(2+))-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α2) adrenoreceptor agonist that mediates intracellular Ca(2+) levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG). METHODS: The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. RESULTS: Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors. CONCLUSION: The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG. Dove 2022-08-19 /pmc/articles/PMC9397435/ /pubmed/36016537 http://dx.doi.org/10.2147/JPR.S378893 Text en © 2022 Xu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Xu, Songchao
Yi, Yusheng
Wang, Yanting
Wang, Pei
Zhao, Yang
Feng, Wei
Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title_full Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title_fullStr Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title_full_unstemmed Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title_short Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats
title_sort dexmedetomidine alleviates neuropathic pain via the trpc6-p38 mapk pathway in the dorsal root ganglia of rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397435/
https://www.ncbi.nlm.nih.gov/pubmed/36016537
http://dx.doi.org/10.2147/JPR.S378893
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