Intradiscal Inflammatory Stimulation Induces Spinal Pain Behavior and Intervertebral Disc Degeneration In Vivo

Abstract

Degeneration of the intervertebral disc (IVD) is known to occur naturally over time, with the severity of pain varying widely. Other components of the degenerative environment, including structural disruption and inflammatory cytokine levels, and their correlation with pain severity have been studied. However, the role of the inflammatory environment in activating degenerative changes that manifest as a pain phenotype has not been elucidated. Previous studies have aimed to recreate the sustained inflammatory environment exhibited during human disc degeneration in a rat model. Most commonly, a puncture injury has been used causing structural damage and only initiating an acute inflammatory response. This study utilized injection of lipopolysaccharide (LPS), a pro-inflammatory stimulus, into the rat disc in vivo to create the desired sustained inflammatory environment independent of physical disruption. LPS injections resulted in upregulation of pro-inflammatory cytokines and an immunogenic response. The structural integrity of the IVD was also altered demonstrated by changes in histological score, disc height, and mechanical properties. Ultimately, a sustained inflammatory environment led to both local and radiating mechanical sensitivity, demonstrating that the pain phenotype experienced during disc degeneration can be initiated solely by a sustained inflammatory profile. Markers indicative of nerve ingrowth into the IVD were also expressed suggesting a potential mechanism for the pain exhibited by animals. This rat injury model will allow for future study of the direct relationship between inflammation and pain in the degenerative environment.