Analgesic effect of dexmedetomidine on regulating BDNF/AKT/CREB signaling pathway in elderly rats with spinal fractures
- VernacularTitle:右美托咪定调控BDNF/AKT/CREB信号通路对老年脊柱骨折大鼠的镇痛效果
- Author:
Airong AN
1
;
Yuefen ZUO
;
Ning ZHANG
;
Baomin SUN
Author Information
- Keywords: dexmedetomidine; spinal fractures; brain-derived neurotrophic factor; protein kinase B; cyclic adenosine monophosphate response element binding protein; signaling pathway; analgesia; neurological function
- From: Journal of Clinical Medicine in Practice 2025;29(9):18-24
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the analgesic effects of different doses of dexmedetomidine(Dex)in regulating the brain-derived neurotrophic factor(BDNF)/protein kinase B(AKT)/cyclica-denosine monophosphate response element binding protein(CREB)signaling pathway in elderly rats with spinal fractures.Methods Sixty rats were randomly divided into control group(skin incision only),model group(spinal fracture without any drug treatment),positive drug group(spinal fracture+0.2 μg/kg sufentanil),low-dose Dex group(spinal fracture+0.4 μg/kg Dex),medium-dose Dex group(spinal fracture+0.6 μg/kg Dex)and high-dose Dex group(spinal fracture+0.8 μg/kg Dex),with ten rats in each group.Mechanical pain threshold and thermal pain threshold were used to assess pain and sedation effects in elderly rats with spinal fractures.Modified neurological severity score(mNSS)was employed to evaluate the degree of neurological dysfunction.Enzyme-linked im-munosorbent assay(ELISA)was performed to detect serotonin(5-HT),substance P(SP),calci-tonin gene-related peptide(CGRP)neurotransmitter levels,tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)inflammatory factor levels.Colorimetric assays were used to measure malon-dialdehyde(MDA)oxidative stress expression levels;kits were applied to determine superoxide dis-mutase(SOD)and catalase(CAT)oxidative stress indicator levels.Western blotting(WB)analy-sis was conducted to examine BDNF,phosphorylated(p)-AKT and p-CREB protein expression lev-els in the spinal dorsal horn tissues of elderly rats with spinal fractures.Results Compared with the control group,the model group showed significantly increased mNSS scores,5-HT,SP,CGRP,TNF-α,IL-1 β and MDA expression levels,and significantly decreased mechanical pain thresholds,thermal pain thresholds,SOD,CAT,as well as BDNF,p-AKT and p-CREB protein expression lev-els(P＜0.05).Compared with the model group,the positive drug group and the medium-and high-dose Dex groups exhibited significantly lower mNSS scores,5-HT,SP,CGRP,TNF-α,IL-1βand MDA expression levels,and significantly higher mechanical pain thresholds,thermal pain thresholds,SOD,CAT,as well as BDNF,p-AKT and p-CREB protein expression levels(P＜0.05).Compared with the positive drug group,the low-dose Dex group had significantly higher mNSS scores,5-HT,SP,CGRP,TNF-α,IL-1 β and MDA expression levels,and significantly low-er mechanical pain thresholds,thermal pain thresholds,as well as BDNF,p-AKT andp-CREB pro-tein expression levels(P＜0.05);the high-dose Dex group showed significantly lower mNSS scores,5-HT,SP,CGRP,TNF-α,IL-1 β and MDA expression levels,and significantly higher me-chanical pain thresholds,thermal pain thresholds,as well as BDNF,p-AKT and p-CREB protein expression levels(P＜0.05).Compared with the low-dose Dex group,the medium-and high-dose Dex groups demonstrated significantly lower mNSS scores,5-HT,SP,CGRP,TNF-α,IL-1 β and MDA expression levels,and significantly higher mechanical pain thresholds,thermal pain thresh-olds,SOD,CAT,as well as BDNF,p-AKT and p-CREB protein expression levels(P＜0.05),in-dicating dose-dependent effect.Conclusion Dex may alleviate pain and reduce its impact on neu-rological function caused by spinal fractures in elderly rats through activation of the BDNF/AKT/CREB signaling pathway.
