Effects of hyaluronic acid applied by different methods on intervertebral disc degeneration: Reduction of inflammation and histological damage via CD44 and RHAMM receptors

This study investigated the effects of epidural (ED) and intradiscal (ID) hyaluronic acid (HA) injections on intervertebral disc degeneration (IDD) in rats. IDD, a common cause of spinal pain and disability, lacks effective treatment options. HA, known for its anti-inflammatory and regenerative properties, has shown potential in managing disc degeneration. The aim was to compare the efficacy of ED and ID HA injections in reducing IDD and promoting disc health. Sixty male Sprague-Dawley rats (10–12 weeks old) were randomly assigned to six different groups. Control (CG) and intervertebral disc degeneration (IDDG); sham (S)+ID, S+ED, IDDG+ED, and IDDG+ID HA injection (0.1 mL, single dose on the day of the procedure) were established in six groups. Histological changes and blood levels of IL-6 and TNF-α were measured. No significant changes in body weight, infection, or mortality were observed. Histologically, the Sham+ID group showed mild disc tears, vacuoles, and serpentine appearance, while the IDDG+ID group displayed indistinct nucleus pulposus(NP) and annulus fibrosus(AF) borders, necrosis, and vacuoles. The IDDG+ED group exhibited regular collagen fibers, reduced vacuoles, and edema, with a complete absence of necrosis. IL-6 and TNF-alpha were elevated in IDDG and Sham+ID groups. However, both cytokines were significantly reduced in the IDDG+ED and IDDG+ID groups. These findings suggest that HA injection reduces inflammation and histological damage, with the epidural method proving more effective than the intradiscal method. HA likely acts by interacting with membrane receptors such as CD44 and RHAMM. No weight change or mortality was observed after HA treatment.