Intervertebral disc injury triggers neurogenic inflammation of adjacent healthy discs.

Calcitonin gene-related peptide Disc-derived low back pain Intervertebral disc degeneration Nerve growth factor Neurogenic inflammation Substance P

Journal

The spine journal : official journal of the North American Spine Society
ISSN: 1878-1632
Titre abrégé: Spine J
Pays: United States
ID NLM: 101130732

Informations de publication

Date de publication:
10 Apr 2024
Historique:
received: 22 10 2023
revised: 14 03 2024
accepted: 04 04 2024
medline: 13 4 2024
pubmed: 13 4 2024
entrez: 12 4 2024
Statut: aheadofprint

Résumé

Intervertebral disc degeneration is common and may play a role in low back pain, but it is not well-understood. Previous studies have shown that the outer layer of the annulus fibrosus of a healthy disc is innervated by nociceptive nerve fibers. In the process of disc degeneration, it can grow into the inner annulus fibrosus or nucleus pulposus and release neuropeptides. Disc degeneration is associated with inflammation that produces inflammatory factors and potentiates nociceptor sensitization. Subsequently neurogenic inflammation is induced by neuropeptide release from activated primary afferent terminals. Because the innervation of a lumbar disc comes from multi-segmental dorsal root ganglion neurons, does neurogenic inflammation in a degenerative disc initiate neurogenic inflammation in neighboring healthy discs by antidromic activity? This study was based on animal experiments in Sprague-Dawley rats to investigate the role of neurogenic inflammation in adjacent healthy disc degeneration induced by disc injury. This was an experimental study. Seventy-five 12-week-old, male Sprague-Dawley rats were allocated to 3 groups (sham group, disc injury group and disc injury+TrkA antagonist group). The disc injury group was punctured in the tail disc between the eighth and ninth coccygeal vertebrae (Co8-9) to establish an animal model of tail intervertebral disc degeneration. The sham group underwent only skin puncture and the disc injury+TrkA antagonist group was intraperitoneally injected with GW441756 two days before disc puncture. The outcome measure included quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Disc injury induced an increase in aggrecan, NGF, TrkA, CGRP, SP, IL-1β, and IL-6 mRNA levels in the injured (Co8-9) and adjacent discs (Co7-8), which reached a peak on day 1, then gradually decreased, and returned to normal on day 14. After intraperitoneal injection of GW441756 prior to puncture, the mRNA levels of the above indicators were down-regulated in Co7-8 and Co8-9 intervertebral discs on the 1st and 7th days. The protein content of the above indicators in Co7-8 and Co8-9 intervertebral discs showed roughly the same trend as mRNA levels. Degeneration of one disc can induce neurogenic inflammation of adjacent healthy discs in a rat model. This model supports a role of neurogenic inflammation in disc degeneration, and may play a role in the experience of low back pain.

Sections du résumé

BACKGROUND CONTEXT BACKGROUND
Intervertebral disc degeneration is common and may play a role in low back pain, but it is not well-understood. Previous studies have shown that the outer layer of the annulus fibrosus of a healthy disc is innervated by nociceptive nerve fibers. In the process of disc degeneration, it can grow into the inner annulus fibrosus or nucleus pulposus and release neuropeptides. Disc degeneration is associated with inflammation that produces inflammatory factors and potentiates nociceptor sensitization. Subsequently neurogenic inflammation is induced by neuropeptide release from activated primary afferent terminals. Because the innervation of a lumbar disc comes from multi-segmental dorsal root ganglion neurons, does neurogenic inflammation in a degenerative disc initiate neurogenic inflammation in neighboring healthy discs by antidromic activity?
PURPOSE OBJECTIVE
This study was based on animal experiments in Sprague-Dawley rats to investigate the role of neurogenic inflammation in adjacent healthy disc degeneration induced by disc injury.
STUDY DESIGN METHODS
This was an experimental study.
METHODS METHODS
Seventy-five 12-week-old, male Sprague-Dawley rats were allocated to 3 groups (sham group, disc injury group and disc injury+TrkA antagonist group). The disc injury group was punctured in the tail disc between the eighth and ninth coccygeal vertebrae (Co8-9) to establish an animal model of tail intervertebral disc degeneration. The sham group underwent only skin puncture and the disc injury+TrkA antagonist group was intraperitoneally injected with GW441756 two days before disc puncture. The outcome measure included quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
RESULTS RESULTS
Disc injury induced an increase in aggrecan, NGF, TrkA, CGRP, SP, IL-1β, and IL-6 mRNA levels in the injured (Co8-9) and adjacent discs (Co7-8), which reached a peak on day 1, then gradually decreased, and returned to normal on day 14. After intraperitoneal injection of GW441756 prior to puncture, the mRNA levels of the above indicators were down-regulated in Co7-8 and Co8-9 intervertebral discs on the 1st and 7th days. The protein content of the above indicators in Co7-8 and Co8-9 intervertebral discs showed roughly the same trend as mRNA levels.
CONCLUSIONS CONCLUSIONS
Degeneration of one disc can induce neurogenic inflammation of adjacent healthy discs in a rat model.
CLINICAL SIGNIFICANCE CONCLUSIONS
This model supports a role of neurogenic inflammation in disc degeneration, and may play a role in the experience of low back pain.

Identifiants

pubmed: 38608821
pii: S1529-9430(24)00162-1
doi: 10.1016/j.spinee.2024.04.002
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no conflicts of interest.

Auteurs

Yongchao Li (Y)

Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, P.R. China.

Chen Dai (C)

Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, P.R. China.

Bing Wu (B)

Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, P.R. China.

Liang Yang (L)

Department of Orthopeadics, Featured Medical Center of Chinese People's Armed Police Forces, Tianjin, P.R. China.

Xiujie Yan (X)

Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, P.R. China.

Tanghua Liu (T)

Algology Institute of Sino-US Zhongguancun Precision Medicine Academy, Beijing, P.R. China.

Jindong Chen (J)

Department of Orthopaedics, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, P.R. China.

Zhaomin Zheng (Z)

Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China; Pain Research Center, Sun Yat-sen University, Guangzhou, P.R. China. Electronic address: zhzhaom@mail.sysu.edu.cn.

Baogan Peng (B)

Department of Orthopaedics, The Third Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, P.R. China. Electronic address: pengbaogan76611@163.com.

Classifications MeSH