Song Yuanlong, Xu Zifen, Zhang Liangpin, Gao Linlin
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, China.
Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, China.
Biomolecules. 2025 Jan 6;15(1):73. doi: 10.3390/biom15010073.
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.
σ-1受体（Sig-1R）已成为疼痛管理领域的一个重要靶点，并一直是广泛研究的对象。然而，其在背根神经节（DRG）神经元炎症性疼痛中的具体功能仍未得到充分阐明。本研究利用全细胞膜片钳技术、单细胞实时PCR和免疫组织化学，研究Sig-1R对完全弗氏佐剂（CFA）诱导的大鼠炎症性疼痛的影响。我们的结果揭示了几个关键发现：（1）发现在炎症性疼痛进展过程中Sig-1R的表达上调，且有从细胞质向细胞膜的显著转位；（2）使用S1RA抑制外周Sig-1R导致CFA诱导的痛觉过敏减轻；（3）通过PRE-084激活Sig-1R导致来自CFA处理大鼠的分离DRG神经元的快速钠电流减少，这与动作电位（AP）峰值和最大去极化速率（MDR）降低以及阈强度增加有关；（4）此外，观察到PRE-084增强钠电流的慢成分，导致阈电位超极化和AP发放频率增加，同时CFA处理大鼠中慢钠通道Nav1.9的mRNA表达升高。总之，我们的研究结果表明，DRG神经元中Sig-1R对钠通道的调节在炎症性疼痛的潜在机制中起重要作用。
