IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model

Abstract

BACKGROUND CONTEXT: Lumbar intervertebral disk herniation (LDH) is a common disease that causes low back pain, radiating leg pain, and sensory impairment. Preclinical studies rely heavily upon standardized animal models of human diseases to predict clinical treatment efficacy and to identify and investigate potential adverse events in human subjects. The current method for making the LDH model involves harvesting the nucleus pulposus (NP) from autologous coccygeal disks and applying to the lumbar nerve roots just proximal to the corresponding dorsal root ganglion. However, this surgical method generates a model that exhibits very different characteristics of disk herniation than that observed in human. PURPOSE: To produce a rat LDH model that better resembles disk herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1b). STUDY DESIGN: Experimental rat LDH model. METHODS: We exposed the L5−6 disk dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disk with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1b) was injected simultaneously to heighten the pathological processes of disk degeneration, including inflammatory responses, matrix destruction, and herniation of the NP. We performed histological staining to assess morphological changes, immunohistochemistry to analyze inflammation-and pain-related expression within and around the puncture site of the L5−6 disk, and real-time polymerase chain reaction to examine expression of markers for degenerative processes. In addition, we performed locomotor tests on the rats. RESULTS: We found that the IL-1b groups showed that the border between the annulus fibrosis and nucleus pulposus was severely interrupted compared to that of the control (puncture only) group. And, the injection of IL-1b leads to accelerated disk degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1b in the exposed disk. CONCLUSIONS: The method proposed here can be used as an index to control the severity of disk degeneration and inflammation through the injected IL-1b concentration concurrent with surgically induced herniation. CLINICAL SIGNIFICANCE: Our proposed model may facilitate research in drug development to evaluate the efficacy of potential therapeutic agents for disk herniation and neuropathic pain and may also be used for nonclinical studies to more accurately assess the effectiveness of various treatment strategies according to the severity of disk degeneration.

The Thermosensitive Injectable Celecoxib-Loaded Chitosan Hydrogel for Repairing Postoperative Intervertebral Disc Defect

“…In fact, studies also showed that the degeneration grade of IVD was aggravated by the accumulation of inflammatory cytokines. TNFα and IL-1β are the important inflammatory factors for intervertebral disc degeneration, which can induce intervertebral disc degeneration by reducing the anabolism of extracellular matrix proteins Hodges;James and Diwan, 2021;Hong;Jeon and Ha, 2021). TNF-α is able to inhibit the production of extracellular matrix and increase the expression of MMP-3, MMP-9, and MMP-13.…”

Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration

“…Inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) are key cytokines involved in aging and age-related diseases, whose expression levels are related to the severity of degeneration to a certain extent ( Krupkova et al, 2018 ; Zhang Y. et al, 2019 ; Kim et al, 2021 ). IL-1 has already been shown to be involved in the pathogenesis of intervertebral disc degeneration ( Phillips et al, 2013 ).…”

“…p16 INK4a , known as a cell cycle suppressor, can inhibit cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), causing stagnation of senescent cells at G1 phase ( Kim et al, 2021 ). The expression level of p16 INK4a increases in senescent cells; thus, p16 INK4a is always used as one of the commonly senescent cell markers (others: SA-β-gal, ki67) ( Krupkova et al, 2018 ; Ogrodnik, 2021 ).…”

The role of IL-6, IL-10, and PGE2 in the treatment of intervertebral disc herniation by dual-channel endoscopic lumbar discectomy

“…Patients with the lumbar intervertebral disc are often accompanied by the inflammatory stress response, and serum-related indicators will increase significantly. There are limited clinical studies on the evaluation of serumrelated indicators of dual-channel endoscopic lumbar intervertebral disc discectomy for LDH patients (20). In this study, dual-channel endoscopic lumbar discectomy was used to treat LDH patients, and IL-6, IL-10, PGE2 and other indicators were used to evaluate the efficacy of surgical treatment, as discussed below.…”