Role of ferroptosis in dorsal root gangions in neuropathic pain in rats
10.3760/cma.j.cn131073.20220714.01113
- VernacularTitle:背根神经节铁死亡在大鼠神经病理性痛中的作用
- Author:
Yifan DENG
1
;
Jianfen LIANG
;
Zhenye ZHANG
;
Ziqing HEI
;
Xiang LI
Author Information
1. 中山大学附属第三医院麻醉科，广州 510630
- Keywords:
Ganglia, spinal;
Ferroptosis;
Neuralgia
- From:
Chinese Journal of Anesthesiology
2022;42(11):1334-1338
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of ferroptosis in the dorsal root gangions in neuropathic pain (NP) in rats.Methods:Thirty-two healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were randomized into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), NP group, NP+ solvent control group (NP+ Veh group), and NP+ liproxstatin-1 (Lip-1) group (NP+ Lip group). NP was induced by chronic constrictive injury (CCI) to sciatic nerve in anesthetized animals.In NP+ Lip group, liproxstatin-1 (diluted to 10 μg/μl in DMSO) 30 μl was intrathecally injected for 3 consecutive days after surgery.NP+ Veh group received intrathecal injection of DMSO 30 μl for 3 consecutive days after surgery.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 3 days before surgery and on days 1, 3, 5, 7 and 10 after surgery.Rats were sacrificed after the end of pain threshold measurement on day 10 after surgery, and DRGs of the lumbar segment (L 3-5) on the left side were removed for determination of the levels of iron ion, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), expression of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot), and expression of ACSL4 in each nerve cells of DRGs (by immunofluorescence) and for microscopic examination of the ultrastructure of mitochondria in DRGs (by transmission electron microscopy). Results:Compared with Sham group, MWT was significantly decreased and TWL was shortened at T 2-6, levels of iron ions, ROS and MDA in DGRs were increased, activities of SOD and GSH-Px were decreased, ACSL4 expression was up-regulated, GPX4 expression was down-regulated, and ACSL4 expression in astrocytes and Schwann cells of DRGs was up-regulated in NP group ( P<0.05). Compared with NP group, MWT was significantly increased and TWL was prolonged at T 3-6, levels of iron ions, ROS and MDA in DGRs were decreased, activities of SOD and GSH-Px were increased, ACSL4 expression was down-regulated, GPX4 expression was up-regulated, and ACSL4 expression in astrocytes and Schwann cells of DRGs was down-regulated ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ Veh group ( P>0.05). The results of electron microscopy showed that collapsed mitochondrial cristae and membrane rupture were found in astrocytes and Schwann cells of DRGs in NP group, and the number of collapsed mitochondrial cristae and membrane rupture was significantly decreased in NP + Lip group when compared with NP group. Conclusions:The ferroptosis in DRGs is involved in NP in rats.
