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Introduction: The present study, investigated the local injection of cerium oxide nanoparticles (CeONPs) into Spinal cord injury (SCI) lesions in rats, and the effect on motor performance and neuropathic pain, together with biochemical markers.Methods: 36 adult male Wistar rats were divided into 4 groups: control group (healthy animals); sham group (laminectomy); SCI group (laminectomy+SCI induction); treatment group (laminectomy + SCI induction + intrathecal injection of 10 µL of CeONPs (1000 µg/mL) immediately after injury). SCI was induced by application of an aneurysm clip at the T12-T13 vertebral region. Immediately after SCI, CeONPs were injected into the treatment group with a Hamilton syringe and micropipet. H&E staining and measurement of the size of the cavity were performed after 6 weeks, and the BBB motor performance test and pain threshold test were performed weekly. GCSF expression, P44/42 MAPK (ERK1/ERK2), P-P44/42 MAPK (ERK1/ERK2), total Tau, total MAG, β-actin were evaluated after 6 weeks.Results: The BBB score and pain threshold improved in animals receiving CeONPs compared with SCI animals. The size of the cavity decreased in the treatment group. GCSF protein expression levels were similar in animals receiving CeONPs compared with the SCI group, but the expression of ERK1/ERK2 and phospho-ERK was lower compared with the SCI group. The expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group.Conclusion: The use of CeONPs in SCI could improve motor functional recovery, reduce pain and increase nerve cell regeneration.

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