Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons
The sigma-1 receptor (Sig-1R) has emerged as a significant target in the realm of pain management and has been the subject of extensive research. Nonetheless, its specific function in inflammatory pain within dorsal root ganglion (DRG) neurons remains inadequately elucidated. This study utilized who...
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2025-01-01
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| author | Yuanlong Song Zifen Xu Liangpin Zhang Linlin Gao |
| author_facet | Yuanlong Song Zifen Xu Liangpin Zhang Linlin Gao |
| author_sort | Yuanlong Song |
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| description | The sigma-1 receptor (Sig-1R) has emerged as a significant target in the realm of pain management and has been the subject of extensive research. Nonetheless, its specific function in inflammatory pain within dorsal root ganglion (DRG) neurons remains inadequately elucidated. This study utilized whole-cell patch clamp techniques, single-cell real-time PCR, and immunohistochemistry to examine the influence of Sig-1R on inflammatory pain induced by complete Freund’s adjuvant (CFA) in a rat model. Our results revealed several key findings: (1) The expression of Sig-1R was found to be upregulated during the progression of inflammatory pain, with a notable translocation from the cytoplasm to the membrane; (2) Inhibition of peripheral Sig-1R using S1RA resulted in a reduction of CFA-induced allodynia; (3) Activation of Sig-1R through PRE-084 led to a decrease in the fast sodium current in isolated DRG neurons from CFA-treated rats, which was associated with a diminished action potential (AP) peak and maximum depolarizing rate (MDR), as well as an increased rheobase; (4) Furthermore, PRE-084 was observed to enhance the slow component of the sodium current, resulting in hyperpolarization of the threshold potential and an increase in AP firing frequency, alongside an elevation in the mRNA expression of the slow sodium channel Nav1.9 in CFA-treated rats. In conclusion, our findings suggest that the modulation of sodium channels by Sig-1R in DRG neurons plays a significant role in the mechanisms underlying inflammatory pain. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-f9c7b026a1fd496ab7868eac0fd5ced72025-01-24T13:25:04ZengMDPI AGBiomolecules2218-273X2025-01-011517310.3390/biom15010073Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG NeuronsYuanlong Song0Zifen Xu1Liangpin Zhang2Linlin Gao3Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, ChinaThe sigma-1 receptor (Sig-1R) has emerged as a significant target in the realm of pain management and has been the subject of extensive research. Nonetheless, its specific function in inflammatory pain within dorsal root ganglion (DRG) neurons remains inadequately elucidated. This study utilized whole-cell patch clamp techniques, single-cell real-time PCR, and immunohistochemistry to examine the influence of Sig-1R on inflammatory pain induced by complete Freund’s adjuvant (CFA) in a rat model. Our results revealed several key findings: (1) The expression of Sig-1R was found to be upregulated during the progression of inflammatory pain, with a notable translocation from the cytoplasm to the membrane; (2) Inhibition of peripheral Sig-1R using S1RA resulted in a reduction of CFA-induced allodynia; (3) Activation of Sig-1R through PRE-084 led to a decrease in the fast sodium current in isolated DRG neurons from CFA-treated rats, which was associated with a diminished action potential (AP) peak and maximum depolarizing rate (MDR), as well as an increased rheobase; (4) Furthermore, PRE-084 was observed to enhance the slow component of the sodium current, resulting in hyperpolarization of the threshold potential and an increase in AP firing frequency, alongside an elevation in the mRNA expression of the slow sodium channel Nav1.9 in CFA-treated rats. In conclusion, our findings suggest that the modulation of sodium channels by Sig-1R in DRG neurons plays a significant role in the mechanisms underlying inflammatory pain.https://www.mdpi.com/2218-273X/15/1/73sigma-1 receptorsingle-cell PCRDRG neuronsvoltage-gated sodium currentNav1.9 |
| spellingShingle | Yuanlong Song Zifen Xu Liangpin Zhang Linlin Gao Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons Biomolecules sigma-1 receptor single-cell PCR DRG neurons voltage-gated sodium current Nav1.9 |
| title | Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons |
| title_full | Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons |
| title_fullStr | Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons |
| title_full_unstemmed | Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons |
| title_short | Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons |
| title_sort | sigma 1 receptor modulates cfa induced inflammatory pain via sodium channels in small drg neurons |
| topic | sigma-1 receptor single-cell PCR DRG neurons voltage-gated sodium current Nav1.9 |
| url | https://www.mdpi.com/2218-273X/15/1/73 |
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