CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice
<b>Background</b>: Referred pain frequently co-exists with visceral pain. However, the exact mechanism governing referred somatic hyperalgesia remains elusive. <b>Methods</b>: By injecting 20% acetic acid into the stomach, we established a mouse model of gastric ulcer (GU). H...
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2025-02-01
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| author | Ziyan Yuan Huanhuan Liu Zhijun Diao Wei Yuan Yuwei Wu Simeng Xue Xinyan Gao Haifa Qiao |
| author_facet | Ziyan Yuan Huanhuan Liu Zhijun Diao Wei Yuan Yuwei Wu Simeng Xue Xinyan Gao Haifa Qiao |
| author_sort | Ziyan Yuan |
| collection | DOAJ |
| description | <b>Background</b>: Referred pain frequently co-exists with visceral pain. However, the exact mechanism governing referred somatic hyperalgesia remains elusive. <b>Methods</b>: By injecting 20% acetic acid into the stomach, we established a mouse model of gastric ulcer (GU). Hematoxylin and eosin (H&E) staining was used as the evaluation criterion for the gastric ulcer model. Evan’s blue (EB) and von Frey tests detected the somatic sensitized area. The DRG neurons distributed among the spinal segments of the sensitized area were prepared for biochemical and electrophysiological experiments. The CCR2 antagonist was intraperitoneally (i.p.) injected into GU mice to test the effect of blocking CCR2 on somatic neurogenic inflammation. <b>Results</b>: GU not only instigated neurogenic plasma extravasation and referred somatic allodynia in the upper back regions spanning the T9 to T11 segments but also augmented the co-expression of T-type Ca<sup>2+</sup> channels and CCR2 and led to the gating properties of T-type Ca<sup>2+</sup> channel alteration in T9–T11 small-diameter DRG neurons. Moreover, the administration of the CCR2 antagonist inhibited the T-type Ca<sup>2+</sup> channel activation, consequently mitigating neurogenic inflammation and referred somatic hyperalgesia. The application of the CCR2 agonist to normal T9–T11 small-diameter DRG neurons simulates the changes in the gating properties of T-type Ca<sup>2+</sup> channel that occur in the GU group. <b>Conclusions</b>: Therefore, these findings indicate that CCR2 may function as a critical regulator in the generation of neurogenic inflammation and mechanical allodynia by modulating the gating properties of the T-type Ca<sup>2+</sup> channels. |
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| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Brain Sciences |
| spelling | doaj-art-7b632ddde11e421bb3fc1be97d8e812b2025-08-20T03:43:15ZengMDPI AGBrain Sciences2076-34252025-02-0115325510.3390/brainsci15030255CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer MiceZiyan Yuan0Huanhuan Liu1Zhijun Diao2Wei Yuan3Yuwei Wu4Simeng Xue5Xinyan Gao6Haifa Qiao7Shaanxi Key Laboratory of Integrative Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaShaanxi Key Laboratory of Integrative Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaShaanxi Key Laboratory of Integrative Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaCollege of Acupuncture-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaCollege of Acupuncture-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaShaanxi Key Laboratory of Integrative Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaCollege of Acupuncture-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaShaanxi Key Laboratory of Integrative Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China<b>Background</b>: Referred pain frequently co-exists with visceral pain. However, the exact mechanism governing referred somatic hyperalgesia remains elusive. <b>Methods</b>: By injecting 20% acetic acid into the stomach, we established a mouse model of gastric ulcer (GU). Hematoxylin and eosin (H&E) staining was used as the evaluation criterion for the gastric ulcer model. Evan’s blue (EB) and von Frey tests detected the somatic sensitized area. The DRG neurons distributed among the spinal segments of the sensitized area were prepared for biochemical and electrophysiological experiments. The CCR2 antagonist was intraperitoneally (i.p.) injected into GU mice to test the effect of blocking CCR2 on somatic neurogenic inflammation. <b>Results</b>: GU not only instigated neurogenic plasma extravasation and referred somatic allodynia in the upper back regions spanning the T9 to T11 segments but also augmented the co-expression of T-type Ca<sup>2+</sup> channels and CCR2 and led to the gating properties of T-type Ca<sup>2+</sup> channel alteration in T9–T11 small-diameter DRG neurons. Moreover, the administration of the CCR2 antagonist inhibited the T-type Ca<sup>2+</sup> channel activation, consequently mitigating neurogenic inflammation and referred somatic hyperalgesia. The application of the CCR2 agonist to normal T9–T11 small-diameter DRG neurons simulates the changes in the gating properties of T-type Ca<sup>2+</sup> channel that occur in the GU group. <b>Conclusions</b>: Therefore, these findings indicate that CCR2 may function as a critical regulator in the generation of neurogenic inflammation and mechanical allodynia by modulating the gating properties of the T-type Ca<sup>2+</sup> channels.https://www.mdpi.com/2076-3425/15/3/255referred somatic hyperalgesiadorsal root ganglionT-type Ca<sup>2+</sup> channelsthe C-C motif chemokine receptor 2Gastric ulcer |
| spellingShingle | Ziyan Yuan Huanhuan Liu Zhijun Diao Wei Yuan Yuwei Wu Simeng Xue Xinyan Gao Haifa Qiao CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice Brain Sciences referred somatic hyperalgesia dorsal root ganglion T-type Ca<sup>2+</sup> channels the C-C motif chemokine receptor 2 Gastric ulcer |
| title | CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice |
| title_full | CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice |
| title_fullStr | CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice |
| title_full_unstemmed | CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice |
| title_short | CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca<sup>2+</sup> Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice |
| title_sort | ccr2 regulates referred somatic hyperalgesia by mediating t type ca sup 2 sup channel currents of small diameter drg neurons in gastric ulcer mice |
| topic | referred somatic hyperalgesia dorsal root ganglion T-type Ca<sup>2+</sup> channels the C-C motif chemokine receptor 2 Gastric ulcer |
| url | https://www.mdpi.com/2076-3425/15/3/255 |
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