Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid...

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Published in:Neurochemistry international 2024-07, Vol.177, p.105764-105764, Article 105764
Main Authors: Niu, Le, Zuo, Chun-Jiang, Zhang, Yong-Ling, Ma, Cui-Xia, Zhou, Xiang-Wen, Sun, Shi-Ru, Tang, Xue-Xue, Huang, Guo-Quan, Zhai, Si-Cheng
Format: Article
Language:English
Subjects:
Animals
Central nervous system
Ganglia, Spinal - drug effects
Ganglia, Spinal - metabolism
Intervertebral Disc Displacement - metabolism
Lower limb pain
Lumbar degeneration
Lumbar Vertebrae
Male
Oligopeptides - pharmacology
Opioid peptides
Oxidative Stress - drug effects
Oxidative Stress - physiology
Rats
Rats, Sprague-Dawley
Reactive oxygen species
Receptors, Opioid, mu - metabolism
Sciatica - drug therapy
Sciatica - metabolism
Spinal Cord - drug effects
Spinal Cord - metabolism
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Summary:Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS. •Mechanical allodynia occurred in LDHS rats.•Spinal EM2 was significantly decreased in LDHS rats.•Decreased spinal EM2 contributed to mechanical allodynia.•Spinal decreased EM2 was induced by increased activity of DPP IV.•Oxidative stress was the causative factor for increased activity of DPP IV.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2024.105764