Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain
Background: Fibromyalgia (FM) is characterized by complex pain symptoms lacking impersonal considerations in diagnosis and treatment evaluation, which often happens in women. Chronic and persistent widespread pain is the key symptom disturbing patients with FM, leading to depression, obesity, and sl...
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MDPI AG
2023-05-01
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| Online Access: | https://www.mdpi.com/2075-1729/13/5/1160 |
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| author | Po-Chih Lai Chia-Ming Yen Ming-Chia Lin Yung-Hsiang Chen Hsien-Yin Liao Yu-Wei Huang Yi-Wen Lin |
| author_facet | Po-Chih Lai Chia-Ming Yen Ming-Chia Lin Yung-Hsiang Chen Hsien-Yin Liao Yu-Wei Huang Yi-Wen Lin |
| author_sort | Po-Chih Lai |
| collection | DOAJ |
| description | Background: Fibromyalgia (FM) is characterized by complex pain symptoms lacking impersonal considerations in diagnosis and treatment evaluation, which often happens in women. Chronic and persistent widespread pain is the key symptom disturbing patients with FM, leading to depression, obesity, and sleep disturbances. Toll-like receptor 4 (TLR4) activation produces a harmful sensory input involved in central pain; this is the focus of this study. Electroacupuncture (EA) has beneficial effects in reducing FM pain, but its connection with TLR4 signaling is still unknown. Methods: Intermittent cold stress significantly induced mechanical and thermal pain. EA, but not sham EA, reliably attenuated mechanical and thermal hyperalgesia. The increased inflammatory mediators in FM mice were reduced in the EA group, but not in the sham group. Results: All TLR4 and related molecule levels increased in the FM mice’s hypothalamus, periaqueductal gray (PAG), and cerebellum. These increases could be attenuated by EA but not sham stimulation. Activation of TLR4 by lipopolysaccharide (LPS) significantly induced FM and can be further reversed by a TLR4 antagonist. Conclusions: These mechanisms provide evidence that the analgesic effect of EA is related to the TLR4 pathway. In addition, we showed that inflammation can activate the TLR4 pathway and provided new possible therapeutic targets for FM pain. |
| first_indexed | 2024-03-11T03:34:55Z |
| format | Article |
| id | doaj.art-e84fec9eea144b02ac3c5a43ef142a10 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T03:34:55Z |
| publishDate | 2023-05-01 |
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| series | Life |
| spelling | doaj.art-e84fec9eea144b02ac3c5a43ef142a102023-11-18T02:09:30ZengMDPI AGLife2075-17292023-05-01135116010.3390/life13051160Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse BrainPo-Chih Lai0Chia-Ming Yen1Ming-Chia Lin2Yung-Hsiang Chen3Hsien-Yin Liao4Yu-Wei Huang5Yi-Wen Lin6College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, TaiwanDepartment of Anesthesiology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, TaiwanDepartment of Nuclear Medicine, E-DA Hospital, College of Medicine, I-Shou University, Kaohsiung 82445, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung 40402, TaiwanCollege of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, TaiwanEmergency and Critical Care Center, E-Da Hospital, Kaohsiung 80708, TaiwanCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, TaiwanBackground: Fibromyalgia (FM) is characterized by complex pain symptoms lacking impersonal considerations in diagnosis and treatment evaluation, which often happens in women. Chronic and persistent widespread pain is the key symptom disturbing patients with FM, leading to depression, obesity, and sleep disturbances. Toll-like receptor 4 (TLR4) activation produces a harmful sensory input involved in central pain; this is the focus of this study. Electroacupuncture (EA) has beneficial effects in reducing FM pain, but its connection with TLR4 signaling is still unknown. Methods: Intermittent cold stress significantly induced mechanical and thermal pain. EA, but not sham EA, reliably attenuated mechanical and thermal hyperalgesia. The increased inflammatory mediators in FM mice were reduced in the EA group, but not in the sham group. Results: All TLR4 and related molecule levels increased in the FM mice’s hypothalamus, periaqueductal gray (PAG), and cerebellum. These increases could be attenuated by EA but not sham stimulation. Activation of TLR4 by lipopolysaccharide (LPS) significantly induced FM and can be further reversed by a TLR4 antagonist. Conclusions: These mechanisms provide evidence that the analgesic effect of EA is related to the TLR4 pathway. In addition, we showed that inflammation can activate the TLR4 pathway and provided new possible therapeutic targets for FM pain.https://www.mdpi.com/2075-1729/13/5/1160electroacupuncturefibromyalgiahypothalamusmicrogliaTLR4cerebellum |
| spellingShingle | Po-Chih Lai Chia-Ming Yen Ming-Chia Lin Yung-Hsiang Chen Hsien-Yin Liao Yu-Wei Huang Yi-Wen Lin Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain Life electroacupuncture fibromyalgia hypothalamus microglia TLR4 cerebellum |
| title | Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain |
| title_full | Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain |
| title_fullStr | Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain |
| title_full_unstemmed | Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain |
| title_short | Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain |
| title_sort | electroacupuncture attenuates fibromyalgia pain via toll like receptor 4 in the mouse brain |
| topic | electroacupuncture fibromyalgia hypothalamus microglia TLR4 cerebellum |
| url | https://www.mdpi.com/2075-1729/13/5/1160 |
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