Curcumin and Curcuminoid Effects Modulating Chronic Mechanical Sensitivity in Spinal Nerve Ligation Model Revert Mitochondria Dysfunction and Oxidative Stress

Abstract Objectives Studies have explored the role of curcumin in the mitigation of neuropathic pain (NP) due to curcumin's antioxidant and anti-inflammatory properties. We evaluated the effects of curcumin C3 complex® (CUR) and bisdemethoxycurcumin (CMO) on the mRNA expression of oxidative stress and mitochondrial dysfunction in nervous tissues (amygdala and spinal cord) that are associated with pain processing in a NP model. Methods Twenty-three animals were randomly assigned to four groups: Sham, spinal cord ligation (SNL), SNL + 100 mg CUR/Kg BW, and SNL + 50 mg CMO/Kg BW for 4 weeks. Mechanical sensitivity was observed by the von Frey test weekly. The lumbosacral section of the spinal cord and the amygdala were collected to determine the mRNA expression of genes related to oxidative stress (SOD1, NRF2, and UQCRC1) and mitochondrial function (MFN1, MFN2, OPA1 for mitochondrial fusion, and PINK1 for mitochondrial fission/mitophagy) utilizing qRT-PCR. Results CUR and CMO significantly decreased the mechanical hypersensitivity in SNL-operated groups, compared to SNL rats. The SNL procedure induced oxidative stress, shown by increased mRNA expression levels of NRF2 as well as decreased mRNA expression levels of SOD1 and UQCRC1. CUR and CMO administration mitigated the negative impacts of SNL on NRF2, SOD1, and UQCRC1 mRNA expression levels in the lumbosacral section of the spinal cord. Both CUR and CMO administration decreased the mRNA expression of MFN1 in the spinal cord and amygdala in SNL rats. CUR and CMO administration decreased OPA1 mRNA expression in the amygdala, while CMO administration increased OPA1 mRNA expression in the spinal cord of SNL rats. Moreover, compared to untreated SNL rats, CUR and CMO administration to SNL rats significantly decreased the mRNA expression of PINK1 in the spinal cord and amygdala. Conclusions CUR and CMO administration decreased mechanical hypersensitivity in SNL-operated rats. Based on the PCR results, CUR and CMO administration reduced SNL-induced oxidative stress and reverted mitochondrial dysfunction. Funding Sources Texas Tech University Health Sciences Center, Lubbock, TX.