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

BACKGROUND CONTEXT

Lumbar intervertebral disc 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 discs 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 disc herniation than that observed in human.

PURPOSE

To produce a rat LDH model that better resembles disc herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1β).

STUDY DESIGN

Experimental rat LDH model.

METHODS

We exposed the L5-6 disc dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disc with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1β) was injected simultaneously to heighten the pathological processes of disc 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 disc, 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-1β 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-1β leads to accelerated disc degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1β in the exposed disc.

CONCLUSIONS

The method proposed here can be used as an index to control the severity of disc degeneration and inflammation through the injected IL-1β 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 disc 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 disc degeneration.