Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration

  • Oxid Med Cell Longev. 2021 May 14:2021:6681815. doi: 10.1155/2021/6681815.
Jiancheng Zheng  1  2  3 ,  Jian Zhang  4 ,  Xingkai Zhang  1  3 ,  Zhiping Guo  2 ,  Wenjian Wu  1  3 ,  Zhe Chen  1  3 ,  Jitian Li  2
Affiliations
  • 1. Department of Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
  • 2. Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Zhengzhou 450000, China.
  • 3. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
  • 4. Department of Spine Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China.
PMID: 34093962 DOI: 10.1155/2021/6681815
Abstract

Reactive Oxygen Species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining. The results suggested a significant correlation between the ROS level and the severity of LBP. Subsequently, a puncture-induced LBP model was established in rats, and ROS levels significantly increased compared with those in the sham surgery group, accompanied with severe puncture-induced IVD degeneration. In addition, when ROS levels were increased by H2O2 administration or decreased by NAC treatment, the rats showed increased or decreased LBP, respectively. Based on this evidence, we further determined that stimulation with H2O2 in nucleus pulposus cells (NPCs) in vivo or in vitro resulted in upregulation of substance P (SP), a peptide thought to be involved in the synaptic transmission of pain, and that the severity of LBP decreased when SP levels were increased by exogenous SP administration or neutralized via aprepitant treatment in the IVDs of rats. In conclusion, ROS are primary inducers of LBP based on clinical and animal data, and the mechanism involves ROS stimulation of NPCs to secrete SP, which is a critical neurotransmitter peptide, to promote LBP in IVDs. Therefore, reducing the level of ROS with specific drugs and inhibiting SP may be alternative methods to treat LBP in the clinic.

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