The Effect of Intra Spinal Administration of Cerium Oxide Nanoparticles on Central pain mechanism: An Experimental Study Running Title: CeONP Administration Effect on Chronic Pain

Abstract

Background: Cerium oxide nanoparticles (CeONPs) have antioxidant and anti-inflammatory attributes. This study investigated its effect on central neuropathic pain (NP), which is resistant to treatment, along with part of the mechanism of action. Materials and Methods: The compressive method of spinal cord injury (SCI) model was used for pain induction. For that purpose, three groups were formed by a random allocation of 24 rats. In the treatment group, CeONPs were injected above and below the lesion site immediately after inducing SCI. We evaluated pain symptoms using acetone, Radian Heat, and Von Frey tests weekly for six weeks. Finally, we counted fibroblasts using H & E staining. We evaluated the expression of Connexin43 (a pain marker), GAD65 (an anti-pain marker), and HDAC2 (an epigenetic marker of pain) proteins using the western blot method. The analysis of results was done by PRISM software. Results: At the end of the study, we found CeONPs reduced pain symptoms to levels similar to those observed in normal animals. CeONPs also increased the expression of GAD65 and CX43 proteins but did not affect HDAC2 inhibition. Conclusion: Our study suggests CeONPs have a pain-alleviating effect on chronic pain, which is likely achieved by preventing the reduction of GAD65 and CX43 protein expression and inhibiting the entry of fibroblasts. These findings give us a new understanding of the potential therapeutic applications of CeONPs for NP management. Further research is needed to validate these findings and explore the optimal dosage and administration of CeONPs for NP treatment.