ANA- 12 inhibits spinal inflammation and alleviates acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.
10.12122/j.issn.1673-4254.2022.02.09
- Author:
Jia Jia ZHAO
1
;
He Yu YANG
1
;
Zhao Di WANG
1
;
Hai Li ZHU
1
;
Min XIE
1
Author Information
1. School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
brain-derived neurotrophic factor;
microglia;
pathological pain;
tropomyosin receptor kinase B;
tumor necrosis factor-α
- MeSH:
Animals;
Brain-Derived Neurotrophic Factor/metabolism*;
Chronic Pain/drug therapy*;
Inflammation;
Rats;
Rats, Sprague-Dawley;
Receptor, trkB/metabolism*
- From:
Journal of Southern Medical University
2022;42(2):232-237
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the inhibitory effect of ANA-12 that blocks brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling on inflammatory pain in rats and explore the underlying mechanism.
METHODS:Forty-two adult SD rats were randomized into BDNF-induced acute pain group (n=24) and CFA-induced chronic pain group. The former group were randomly divided into 4 subgroups, including a control group, ANA-12 treatment group, BDNF treatment group, and BDNF+ANA-12 treatment group; the latter group were subgrouped into control group, CFA treatment group (CFA) and CFA + ANA-12 treatment group. The effects of ANA-12 treatment on pain behaviors of the rats with BDNF-induced acute pain and CFA-induced chronic inflammatory pain were observed. Western blotting was used to examine TrkB signaling and expressions of microglia marker protein Iba1 and TNF-α in the spinal cord of the rats.
RESULTS:BDNF injection into the subarachnoid space significantly increased the number of spontaneous paw withdrawal of the rats (P < 0.05), which was obviously reduced by ANA-12 treatment (P < 0.05). The rats with intraplantar injection of CFA, showed significantly increased ipsilateral mechanical stimulation sensitivity (P < 0.05), and ANA-12 treatment obviously increased the ipsilateral foot withdrawal threshold (P < 0.05). Treatment with either BDNF or CFA significantly increased the phosphorylation level of TrkB (Y705) in the spinal cord of the rats (P < 0.05), which was significantly lowered by ANA-12 treatment (P < 0.05). Treatment with BDNF and CFA both significantly up-regulated the expressions of Iba1 and TNF-α in the spinal cord (P < 0.05), but ANA-12 significantly reduced their expression levels (P < 0.05).
CONCLUSION:ANA-12 can reduce spinal cord inflammation and relieve acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.
