Peng BG, Li YC, Yang L. Role of neurogenic inflammation in intervertebral disc degeneration. World J Orthop 2025; 16(1): 102120 [PMID: 39850033 DOI: 10.5312/wjo.v16.i1.102120]
Corresponding Author of This Article
Bao-Gan Peng, MD, PhD, Chief Physician, Professor, Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People’s Liberation Army, No. 69 Yongding Road, Beijing 100039, China. pengbaogan@163.com
Research Domain of This Article
Orthopedics
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Orthop. Jan 18, 2025; 16(1): 102120 Published online Jan 18, 2025. doi: 10.5312/wjo.v16.i1.102120
Role of neurogenic inflammation in intervertebral disc degeneration
Bao-Gan Peng, Yong-Chao Li, Liang Yang
Bao-Gan Peng, Yong-Chao Li, Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing 100039, China
Liang Yang, Department of Orthopeadics, Featured Medical Center of Chinese People’s Armed Police Forces, Tianjin 300000, China
Author contributions: Peng BG, Li YC, and Yang L analyzed the data and wrote the manuscript; all authors read and approved the final manuscript; All authors contributed equally to this study.
Conflict-of-interest statement: The authors report having no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Gan Peng, MD, PhD, Chief Physician, Professor, Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People’s Liberation Army, No. 69 Yongding Road, Beijing 100039, China. pengbaogan@163.com
Received: October 9, 2024 Revised: November 29, 2024 Accepted: December 20, 2024 Published online: January 18, 2025 Processing time: 96 Days and 0.2 Hours
Abstract
In healthy intervertebral discs (IVDs), nerves and blood vessels are present only in the outer annulus fibrosus, while in degenerative IVDs, a large amount of nerve and blood vessel tissue grows inward. Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration. Recently, non-neuronal cells, including IVD cells and infiltrating immune cells, have emerged as important players in neurogenic inflammation. IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system. In return, IVD cells and immune cells produce neuropeptides and nerve growth factor, which stimulate nerve fibers. This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD. Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs. These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs. Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.
Core Tip: The outer layer of the annulus fibrosus and the vertebral endplate are innervated by nociceptive nerves fibers. Injury to the annulus fibrosus or endplate excites nociceptive stimuli, releasing neuropeptides such as substance P and calcitonin gene related peptide, which results in neurogenic inflammation within the intervertebral disc. Neurogenic inflammation further leads to progressive disc degeneration and chronic discogenic pain through complex interactions between the nervous and immune systems.
