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Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms
OBJECTIVE: N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466914/ https://www.ncbi.nlm.nih.gov/pubmed/27381504 http://dx.doi.org/10.1136/acupmed-2015-010986 |
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author | Lu, Kung-Wen Hsieh, Ching-Liang Yang, Jun Lin, Yi-Wen |
author_facet | Lu, Kung-Wen Hsieh, Ching-Liang Yang, Jun Lin, Yi-Wen |
author_sort | Lu, Kung-Wen |
collection | PubMed |
description | OBJECTIVE: N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model. METHODS: A model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry. RESULTS: Acid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18±0.27 g, p<0.05 vs controls), which was reversed by EA (4.23±0.33 g, p<0.05 vs FM group) but not by MA (2.37±0.14 g, p<0.05 vs EA group). Expression levels of phosphorylated N-methyl-D-aspartate receptor (pNR)1 and pNR2B were significantly increased in the dorsal root ganglion of FM model mice (132.21±14.4% and 116.69±3.22% of control values), whereas NR1 and NR2B levels were unchanged (97.31±3.79% and 97.07%±2.27%, respectively). Expression levels of pCaMKIIα and pCREB were also higher in the FM group, and these changes were reversed by EA but not by MA. Similar changes in expression were observed in spinal cord neurons. CONCLUSIONS: Reduced NMDAR−CaMKIIα−pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment. |
format | Online Article Text |
id | pubmed-5466914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54669142017-07-19 Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms Lu, Kung-Wen Hsieh, Ching-Liang Yang, Jun Lin, Yi-Wen Acupunct Med Original Paper OBJECTIVE: N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model. METHODS: A model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry. RESULTS: Acid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18±0.27 g, p<0.05 vs controls), which was reversed by EA (4.23±0.33 g, p<0.05 vs FM group) but not by MA (2.37±0.14 g, p<0.05 vs EA group). Expression levels of phosphorylated N-methyl-D-aspartate receptor (pNR)1 and pNR2B were significantly increased in the dorsal root ganglion of FM model mice (132.21±14.4% and 116.69±3.22% of control values), whereas NR1 and NR2B levels were unchanged (97.31±3.79% and 97.07%±2.27%, respectively). Expression levels of pCaMKIIα and pCREB were also higher in the FM group, and these changes were reversed by EA but not by MA. Similar changes in expression were observed in spinal cord neurons. CONCLUSIONS: Reduced NMDAR−CaMKIIα−pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment. BMJ Publishing Group 2017-02 2016-07-05 /pmc/articles/PMC5466914/ /pubmed/27381504 http://dx.doi.org/10.1136/acupmed-2015-010986 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Original Paper Lu, Kung-Wen Hsieh, Ching-Liang Yang, Jun Lin, Yi-Wen Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title | Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title_full | Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title_fullStr | Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title_full_unstemmed | Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title_short | Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl-D-aspartate receptors and related mechanisms |
title_sort | effects of electroacupuncture in a mouse model of fibromyalgia: role of n-methyl-d-aspartate receptors and related mechanisms |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466914/ https://www.ncbi.nlm.nih.gov/pubmed/27381504 http://dx.doi.org/10.1136/acupmed-2015-010986 |
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