Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models

Neuropathic pain (NP) is a common symptom of many diseases and is caused by direct or indirect damage to the nervous system. Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors are typical drugs used in clinical practice to suppress pain. However, these drugs have drawbacks, i...

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Main Authors: Kai Zhang, Rui Ran, Cheng-Jun Zhang, Linna Wang, Hai-Hong Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1555732/full
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author Kai Zhang
Kai Zhang
Rui Ran
Rui Ran
Cheng-Jun Zhang
Linna Wang
Hai-Hong Zhang
Hai-Hong Zhang
author_facet Kai Zhang
Kai Zhang
Rui Ran
Rui Ran
Cheng-Jun Zhang
Linna Wang
Hai-Hong Zhang
Hai-Hong Zhang
author_sort Kai Zhang
collection DOAJ
description Neuropathic pain (NP) is a common symptom of many diseases and is caused by direct or indirect damage to the nervous system. Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors are typical drugs used in clinical practice to suppress pain. However, these drugs have drawbacks, including a short duration of action, a limited analgesic effect, and possible dependence and side effects. Therefore, developing more effective NP treatment strategies has become a priority in medical research and has attracted much research attention. P2X7 receptor (P2X7R) is a non-selective cation channel activated by adenosine triphosphate and is mainly expressed in microglia in the central nervous system. Microglial P2X7R plays an important role in pain regulation, suggesting that it could be a potential target for drug development. This review comprehensively and objectively discussed the latest research progress of P2X7R, including its structural characteristics, functional properties, relationship with microglial activation and polarization, mechanism of action, and potential therapeutic strategies in multiple NP models. This study aimed to provide in-depth insights into the association between P2X7R and NP and explore the mechanism of action of P2X7R in the pathological process of NP and the translational potential and clinical application prospects of P2X7R antagonists in pain treatment, providing a scientific basis for the precise treatment of NP.
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issn 1663-9812
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publishDate 2025-03-01
publisher Frontiers Media S.A.
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spelling doaj-art-85937a5c31d94c8db824c4cdb07adf882025-08-20T02:40:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15557321555732Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain modelsKai Zhang0Kai Zhang1Rui Ran2Rui Ran3Cheng-Jun Zhang4Linna Wang5Hai-Hong Zhang6Hai-Hong Zhang7Department of Orthopedics, The Second Hospital of Lanzhou University, Lanzhou, ChinaOrthopedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopedics, The Second Hospital of Lanzhou University, Lanzhou, ChinaOrthopedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou Biotechnique Development Co., Ltd., Lanzhou, ChinaLanzhou Biotechnique Development Co., Ltd., Lanzhou, ChinaDepartment of Orthopedics, The Second Hospital of Lanzhou University, Lanzhou, ChinaOrthopedics Key Laboratory of Gansu Province, Lanzhou, ChinaNeuropathic pain (NP) is a common symptom of many diseases and is caused by direct or indirect damage to the nervous system. Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors are typical drugs used in clinical practice to suppress pain. However, these drugs have drawbacks, including a short duration of action, a limited analgesic effect, and possible dependence and side effects. Therefore, developing more effective NP treatment strategies has become a priority in medical research and has attracted much research attention. P2X7 receptor (P2X7R) is a non-selective cation channel activated by adenosine triphosphate and is mainly expressed in microglia in the central nervous system. Microglial P2X7R plays an important role in pain regulation, suggesting that it could be a potential target for drug development. This review comprehensively and objectively discussed the latest research progress of P2X7R, including its structural characteristics, functional properties, relationship with microglial activation and polarization, mechanism of action, and potential therapeutic strategies in multiple NP models. This study aimed to provide in-depth insights into the association between P2X7R and NP and explore the mechanism of action of P2X7R in the pathological process of NP and the translational potential and clinical application prospects of P2X7R antagonists in pain treatment, providing a scientific basis for the precise treatment of NP.https://www.frontiersin.org/articles/10.3389/fphar.2025.1555732/fullneuropathic painP2X7RmicrogliaM1/M2 polarizationcytokineneuroinflammation
spellingShingle Kai Zhang
Kai Zhang
Rui Ran
Rui Ran
Cheng-Jun Zhang
Linna Wang
Hai-Hong Zhang
Hai-Hong Zhang
Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
Frontiers in Pharmacology
neuropathic pain
P2X7R
microglia
M1/M2 polarization
cytokine
neuroinflammation
title Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
title_full Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
title_fullStr Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
title_full_unstemmed Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
title_short Focus on P2X7R in microglia: its mechanism of action and therapeutic prospects in various neuropathic pain models
title_sort focus on p2x7r in microglia its mechanism of action and therapeutic prospects in various neuropathic pain models
topic neuropathic pain
P2X7R
microglia
M1/M2 polarization
cytokine
neuroinflammation
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1555732/full
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