Effect of spinal reelin protein expression on neuropathic pain in rats
10.3760/cma.j.cn431274-20241018-01571
- VernacularTitle:脊髓Reelin蛋白表达对大鼠神经性疼痛的影响
- Author:
Jingjin LI
1
;
Zhonghai WANG
;
Bin ZENG
;
Hongwei LI
Author Information
1. 郴州市第一人民医院麻醉科，郴州 423001
- Publication Type:Journal Article
- Keywords:
Reelin protein;
Calcium-calmodulin-dependent protein kinase type 2;
Extracellular signal-regulated kinase 1/2;
Neuropathic pain
- From:
Journal of Chinese Physician
2025;27(9):1355-1360
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of spinal Reelin protein (RELN) in neuropathic pain and its related mechanisms.Methods:A rat model of neuropathic pain induced by chronic constriction injury (CCI) was established using the sciatic nerve ligation method. The mechanical threshold and thermal threshold of the injured side and contralateral side in the sham-operation group and CCI group were compared. Western blot was used to detect the differences in the expressions of spinal RELN, calcium/calmodulin-dependent protein kinase Ⅱ (CAMKⅡ) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) proteins. On the 7th day after CCI modeling, the CCI model rats were further divided into three groups: CCI group (without any treatment), CCI+ RELN overexpression group (intrathecal injection of 15 μl of 5 μg/μl RELN overexpression plasmid, once a day for 2 consecutive days) and CCI+ PBS group (intrathecal injection of PBS). The mechanical threshold and thermal threshold among the three groups were compared, and Western blot was used again to detect the differences in the expressions of RELN, CaMKⅡ and p-ERK1/2 proteins in the three groups.Results:CCI successfully induced neuropathic pain in rats. On the 7th day after CCI, compared with the contralateral hind paw or the injured hind paw in the sham-operation group, the mechanical threshold and thermal threshold of the injured hind paw in the CCI group were significantly lower, with statistically significant differences (all P<0.001). Western blot results showed that compared with the sham-operation group, the protein expression of RELN in the spinal dorsal horn of the injured side in the CCI group was lower ( P=0.031), the protein expression of CAMKⅡ and the level of p-ERK1/2 were higher (all P<0.05), and there was no statistically significant difference in the level of ERK1/2 among the groups ( P>0.05). The thermal threshold and mechanical threshold of the injured side in the CCI+ RELN overexpression group were significantly higher than those in the CCI group and CCI+ PBS group (all P<0.05). Western blot results showed that 24 hours after the transfection of RELN overexpression plasmid, compared with the CCI+ PBS group, the protein expression of RELN in the CCI+ RELN overexpression group was significantly increased, with a statistically significant difference ( P<0.05), indicating that the transfection of RELN overexpression plasmid was successful. Compared with the CCI+ PBS group, the protein expression of CAMKⅡ and the phosphorylation level of ERK2 in the CCI+ RELN overexpression group were lower (all P<0.05), while there was no statistically significant difference in the phosphorylation level of ERK1 ( P>0.05). Conclusions:The overexpression of the RELN gene in the spinal cord weakens the maintenance of neuropathic pain by inhibiting the activation of the CAMKⅡ/ERK2 pathway, which suggests that RELN may become a new target for pain treatment.
