Reactive Oxygen Species Induced Upregulation of TRPV1 in Dorsal Root Ganglia Results in Low Back Pain in Rats

Abstract

Background

Dorsal root ganglia (DRGs) contain sensory neurons that innervate intervertebral discs (IVDs) and may play a critical role in mediating low-back pain (LBP), but the potential pathophysiological mechanism needs to be clarified.

Methods

A discogenic LBP model in rats was established by penetration of a lumbar IVD. The severity of LBP was evaluated through behavioral analysis, and the gene and protein expression levels of pro-algesic peptide substance P (SP) and calcitonin gene–related peptide (CGRP) in DRGs were quantified. The level of reactive oxygen species (ROS) in bilateral lumbar DRGs was also quantified using dihydroethidium staining. Subsequently, hydrogen peroxide solution or N-acetyl-L-cysteine was injected into DRGs to evaluate the change in LBP, and gene and protein expression levels of transient receptor potential vanilloid-1 (TRPV1) in DRGs were analyzed. Finally, an inhibitor or activator of TRPV1 was injected into DRGs to observe the change in LBP.

Results

The rats had remarkable LBP after disc puncture, manifesting as mechanical and cold allodynia and increased expression of the pro-algesic peptides SP and CGRP in DRGs. Furthermore, there was significant overexpression of ROS in bilateral lumbar DRGs, while manipulation of the level of ROS in DRGs attenuated or aggravated LBP in rats. In addition, excessive ROS in DRGs stimulated upregulation of TRPV1 in DRGs. Finally, activation or inhibition of TRPV1 in DRGs resulted in a significant increase or decrease of discogenic LBP, respectively, suggesting that ROS-induced TRPV1 has a strong correlation with discogenic LBP.

Conclusion

Increased ROS in DRGs play a primary pathological role in puncture-induced discogenic LBP, and excessive ROS–induced upregulation of TRPV1 in DRGs may be the underlying pathophysiological mechanism to cause nerve sensitization and discogenic LBP. Therapeutic targeting of ROS or TRPV1 in DRGs may provide a promising method for the treatment of discogenic LBP.

Keywords:

• lower back pain
• reactive oxygen species
• dorsal root ganglion
• transient receptor potential vanilloid-1
• substance p
• calcitonin gene related peptide
• intervertebral disc

Abbreviations

LBP, low back pain; IVD, intervertebral disc; DRG, dorsal root ganglion; ROS, reactive oxygen species; TRPV1, transient receptor potential vanilloid-1; SP, substance P; CGRP, calcitonin gene related peptide.

Data Sharing Statement

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgments

This work was supported by a grant from the Science and Technology Development Fund Project (Grant No. QKY2023-19) of Qingpu District, and the Health Commission research project (Grant No. QWJ2023-06) in Qingpu District. We would appreciate the contribution from Mrs djt.C for the illustration of Figure 5. We thank LetPub (Accdon LLC) for its linguistic assistance during the preparation of this manuscript.

Disclosure

The authors declare no conflicts of interest regarding the publication of this paper.