Analgesic Effect and Mechanism of Osteoking on Dorsal Root Ganglion Compression Model Rats
10.13422/j.cnki.syfjx.20231645
- VernacularTitle:恒古骨伤愈合剂对背根节压迫模型大鼠的镇痛作用及机制
- Author:
Wuqiong HOU
1
;
Ying ZONG
2
;
Fangting ZHOU
2
;
Sensen LI
2
;
Liting XU
2
;
Xueying TAO
2
;
Chunfang LIU
2
;
Chao WANG
2
;
Na LIN
1
Author Information
1. Chengde Medical University， Chengde 067000， China
2. Institute of Chinese Materia Medica， China Academy of Chinese Medicine Sciences， Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
Osteoking;
nerve compression in lumbar disc herniation;
chronic compression of dorsal root ganglion （CCD）;
neuropathic pain;
neuroactive ligand-receptor signaling pathway;
hypoxia-inducible factor-1 （HIF-1） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(24):30-41
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the analgesic effect and mechanism of Osteoking （OK） on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion （CCD） was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group， low， medium， and high dose OK groups （1.31， 2.63， 5.25 mL·kg-1·d-1）， and pregabalin group （5 mg·kg-1）， with eight rats in each group. Another eight SD rats were taken as the blank group， and the same volume of normal saline was given by gavage. Behavioral tests， side effect evaluation， network analysis， Western blot， immunofluorescence， and antagonist application were used to explore the effect. ResultCompared with the blank group， the mechanical hyperalgesia threshold， thermal hyperalgesia threshold， and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased （P<0.01）， and the related indicators of the affected foot footprints are significantly down-regulated （P<0.01）. The expression of signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， and phosphorylated extracellular regulated protein kinase （p-ERK） in microglia in the spinal dorsal horn is significantly increased in the model group （P<0.01）. Compared with the model group， low， medium， and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats （P<0.05， P<0.01） in a dose-dependent manner， improve the gait of CCD rats （P<0.05， P<0.01）， and reduce the expression of inflammatory factors in the spinal dorsal horn （P<0.05， P<0.01）. The expression of STAT3， VEGFA， and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased （P<0.05， P<0.01）， and the acetic acid-induced nociceptive response in rats is effectively reduced （P<0.05， P<0.01）. In addition， there is no tolerance. The results of the body mass test， organ index， forced swimming， and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group （P<0.01）. ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects， and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3， VEGFA， p-ERK， and other elements in microglia.
