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Moving Toward Objective Diagnosis in Fibromyalgia: Emerging Biomarkers and Digital Phenotyping Tools
 
 
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Volume 14
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10.3390/biomedicines14030584
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Article

Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice

by
Hung-Yu Huang
1,2,
Younbyoung Chae
3,
Ming-Chia Lin
4,
I-Han Hsiao
5,6,
Hsin-Cheng Hsu
7,
Chien-Yi Ho
8,9,10,11 and
Yi-Wen Lin
1,12,*
1
Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung 404328, Taiwan
2
Department of Neurology, China Medical University Hospital, Taichung 404327, Taiwan
3
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02453, Republic of Korea
4
Department of Nuclear Medicine, E-DA Hospital, I-Shou University, Kaohsiung 82445, Taiwan
5
School of Medicine, College of Medicine, China Medical University, Taichung 404328, Taiwan
6
Department of Neurosurgery, China Medical University Hospital, Taichung 404327, Taiwan
7
Department of Traditional Chinese Medicine, China Medical University Hsinchu Hospital, Hsinchu 302233, Taiwan
8
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404328, Taiwan
9
Division of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu 302233, Taiwan
10
Physical Examination Center, China Medical University Hsinchu Hospital, Hsinchu 302233, Taiwan
11
Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302233, Taiwan
12
Chinese Medicine Research Center, China Medical University, Taichung 404328, Taiwan
 
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Biomedicines 2026, 14(3), 584; https://doi.org/10.3390/biomedicines14030584
Submission received: 13 January 2026 / Revised: 20 February 2026 / Accepted: 2 March 2026 / Published: 5 March 2026
(This article belongs to the Special Issue Fibromyalgia and Neuroinflammation: Unraveling Pathophysiological Links and Therapeutic Targets)
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Abstract

Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both for individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand 1 (PD-L1)/PD-1 were first identified to be involved in cancer immunotherapy, and their application to pain management has not been yet investigated. Methods: In this study, we aimed to explore the mechanism underlying the action of PD-L1 on the PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, and transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1-neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia management.
Keywords: fibromyalgia; electroacupuncture; PD-L1; Trpv1; neutralization; cerebellum fibromyalgia; electroacupuncture; PD-L1; Trpv1; neutralization; cerebellum

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MDPI and ACS Style

Huang, H.-Y.; Chae, Y.; Lin, M.-C.; Hsiao, I.-H.; Hsu, H.-C.; Ho, C.-Y.; Lin, Y.-W. Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice. Biomedicines 2026, 14, 584. https://doi.org/10.3390/biomedicines14030584

AMA Style

Huang H-Y, Chae Y, Lin M-C, Hsiao I-H, Hsu H-C, Ho C-Y, Lin Y-W. Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice. Biomedicines. 2026; 14(3):584. https://doi.org/10.3390/biomedicines14030584

Chicago/Turabian Style

Huang, Hung-Yu, Younbyoung Chae, Ming-Chia Lin, I-Han Hsiao, Hsin-Cheng Hsu, Chien-Yi Ho, and Yi-Wen Lin. 2026. "Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice" Biomedicines 14, no. 3: 584. https://doi.org/10.3390/biomedicines14030584

APA Style

Huang, H.-Y., Chae, Y., Lin, M.-C., Hsiao, I.-H., Hsu, H.-C., Ho, C.-Y., & Lin, Y.-W. (2026). Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice. Biomedicines, 14(3), 584. https://doi.org/10.3390/biomedicines14030584

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