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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Frontiers Media S.A.
2025-03-01
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| 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. |
| format | Article |
| id | doaj-art-85937a5c31d94c8db824c4cdb07adf88 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| 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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