SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107
- VernacularTitle:SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛
- Author:
Ming WEI
1
;
Feng-jiao GAO
1
;
Lin YANG
2
;
Lai-bao SUN
1
;
Xue-nong ZOU
3
;
Wen-qi HUANG
1
Author Information
1. Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
2. Department of Anesthesiology, Panyu Central Hospital, Guangzhou 511400, China
3. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou 510700, China
- Publication Type:Journal Article
- Keywords:
lumbar disc herniation;
nucleus pulposus;
radicular pain;
SDF-1;
CXCR4
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(3):373-380
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of SDF-1/CXCR4 in radicular pain induced by autograft of nucleus pulposus. MethodsThree parts were included. ① 26 rats were randomly divided into sham group and model group. Autograft of nucleus pulposus was done in model group. Paw withdrawal threshold (PWT) was tested by von Fray filaments. The expression of SDF-1, CXCR4, pERK and pAKT of spinal cord was tested by western blot. Immunofluorescence staining was used to locate the expression of SDF-1 and CXCR4. ② 54 rats were randomly and equally divided into sham group, model group, vehicle group, SDF-1 neutralizing antibody group, AMD3100 group, and isotype IgG group. Drug was administered intrathecally. PWT and the expression of pERK and pAKT of spinal cord were tested. ③ 18 rats were randomly and equally divided into model group, U0126 group and LY294002 group. Drug was administered intrathecally. PWT was tested. Results① Autologous nucleus pulposus transplantation in rats reduced PWT (P<0.001) and increased the expressions of SDF-1, CXCR4, pERK and pAKT in spinal cord of rats (P<0.05). SDF-1 was mainly co-expressed with neuron, while CXCR4 was co-expressed with neuron and astrocyte. ② SDF-1 neutralizing antibody and CXCR4 inhibitor AMD3100 reduced PWT (P<0.05). The expression of pERK and pAKT in spinal cord of SDF-1 neutralizing antibody group and AMD3100 group was reduced (P<0.05). ③ Intrathecally administration of MEK inhibitor U0126 or PI3K inhibitor LY294002 reduced PWT (P<0.05). ConclusionSDF-1/CXCR4 activates ERK and PI3K/AKT signaling, which contributes to the pathogenesis of radicular pain induced by autograft of nucleus pulposus.