Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model

<b>Background:</b> Fibromyalgia, a chronic condition that causes long-lasting pain over several months, is a global medical issue with both personal and societal implications. It is one of the hardest types of pain to heal, given the lack of objective parameters for diagnosis and progres...

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Main Authors: Huan-Chin Lin, Hsin-Cheng Hsu, Hsien-Yin Liao, Arbee L.P. Chen, Yi-Wen Lin
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/2/396
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author Huan-Chin Lin
Hsin-Cheng Hsu
Hsien-Yin Liao
Arbee L.P. Chen
Yi-Wen Lin
author_facet Huan-Chin Lin
Hsin-Cheng Hsu
Hsien-Yin Liao
Arbee L.P. Chen
Yi-Wen Lin
author_sort Huan-Chin Lin
collection DOAJ
description <b>Background:</b> Fibromyalgia, a chronic condition that causes long-lasting pain over several months, is a global medical issue with both personal and societal implications. It is one of the hardest types of pain to heal, given the lack of objective parameters for diagnosis and progression evaluation. The main symptoms of fibromyalgia are long-lasting widespread pain alongside with anxiety, fatigue, sleep disorders, cognitive dysfunction, and obesity. Programmed cell death 1 ligand 1 (PD-L1) has been used as a target in cancer immunotherapy. It can inhibit acute and chronic pain by suppressing nociceptive neuron activity via PD-1 receptors. <b>Methods</b>: The current study aimed to investigate the role of PD-L1/PD1 in a mouse fibromyalgia pain model. Mice were exposed to intermittent cold stress (ICS) to produce a murine fibromyalgia model characterized using von Frey and Hargreaves tests. <b>Results</b>: The ICS-induced mice fibromyalgia pain model showed mechanical (2.26 ± 0.18 g) and thermal (4.36 ± 0.31 s) hyperalgesia. Nociceptive responses could be relieved with electroacupuncture, intracerebral PD-L1 injection, or <i>Trpv1</i> deletion. We also identified a lower PD-1 level in the dorsal root ganglion, spinal cord, thalamus, and somatosensory cortex. In contrast, levels of pain-related kinases increased after fibromyalgia induction, an effect which could be reversed by EA, PD-L1, or <i>Trpv1</i> deletion. <b>Conclusions</b>: Our findings shed light on the contribution of PD-L1/PD1 to EA and fibromyalgia pain, indicating its potential as a treatment target for fibromyalgia.
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spelling doaj-art-388074f1c63246f89e0d4eec2a84c4a42025-08-20T02:44:55ZengMDPI AGBiomedicines2227-90592025-02-0113239610.3390/biomedicines13020396Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain ModelHuan-Chin Lin0Hsin-Cheng Hsu1Hsien-Yin Liao2Arbee L.P. Chen3Yi-Wen Lin4College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 404328, TaiwanDepartment of Traditional Chinese Medicine, China Medical University Hsinchu Hospital, China Medical University, Hsinchu 302056, TaiwanCollege of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404328, TaiwanDepartment of Computer Science and Information Engineering, Asia University, Taichung 413305, TaiwanCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 404328, Taiwan<b>Background:</b> Fibromyalgia, a chronic condition that causes long-lasting pain over several months, is a global medical issue with both personal and societal implications. It is one of the hardest types of pain to heal, given the lack of objective parameters for diagnosis and progression evaluation. The main symptoms of fibromyalgia are long-lasting widespread pain alongside with anxiety, fatigue, sleep disorders, cognitive dysfunction, and obesity. Programmed cell death 1 ligand 1 (PD-L1) has been used as a target in cancer immunotherapy. It can inhibit acute and chronic pain by suppressing nociceptive neuron activity via PD-1 receptors. <b>Methods</b>: The current study aimed to investigate the role of PD-L1/PD1 in a mouse fibromyalgia pain model. Mice were exposed to intermittent cold stress (ICS) to produce a murine fibromyalgia model characterized using von Frey and Hargreaves tests. <b>Results</b>: The ICS-induced mice fibromyalgia pain model showed mechanical (2.26 ± 0.18 g) and thermal (4.36 ± 0.31 s) hyperalgesia. Nociceptive responses could be relieved with electroacupuncture, intracerebral PD-L1 injection, or <i>Trpv1</i> deletion. We also identified a lower PD-1 level in the dorsal root ganglion, spinal cord, thalamus, and somatosensory cortex. In contrast, levels of pain-related kinases increased after fibromyalgia induction, an effect which could be reversed by EA, PD-L1, or <i>Trpv1</i> deletion. <b>Conclusions</b>: Our findings shed light on the contribution of PD-L1/PD1 to EA and fibromyalgia pain, indicating its potential as a treatment target for fibromyalgia.https://www.mdpi.com/2227-9059/13/2/396electroacupuncturefibromyalgiaPD-L1TRPV1spinal cordsomatosensory cortex
spellingShingle Huan-Chin Lin
Hsin-Cheng Hsu
Hsien-Yin Liao
Arbee L.P. Chen
Yi-Wen Lin
Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
Biomedicines
electroacupuncture
fibromyalgia
PD-L1
TRPV1
spinal cord
somatosensory cortex
title Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
title_full Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
title_fullStr Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
title_full_unstemmed Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
title_short Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model
title_sort electroacupuncture modulates programmed cell death 1 ligand 1 on peripheral and central nervous systems in a mouse fibromyalgia pain model
topic electroacupuncture
fibromyalgia
PD-L1
TRPV1
spinal cord
somatosensory cortex
url https://www.mdpi.com/2227-9059/13/2/396
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