Emerging evidence shows that the gut microbiota plays an important role in neuropathic pain (NP) via the gut–brain axis. Male rats were divided into sham, spinal nerve ligation (SNL), SNL + 200 mg GEG/kg BW (GEG200), and SNL + 600 mg GEG/kg BW (GEG600) for 5 weeks. The dosages of 200 and 600 mg GEG/kg BW for rats correspond to 45 g and 135 g raw ginger for human daily consumption, respectively. Both GEG groups mitigated SNL-induced NP behavior. GEG-supplemented animals had a decreased abundance of Rikenella, Muribaculaceae, Clostridia UCG-014, Mucispirillum schaedleri, RF39, Acetatifactor, and Clostridia UCG-009, while they had an increased abundance of Flavonifactor, Hungatella, Anaerofustis stercorihominis, and Clostridium innocuum group. Relative to sham rats, Fos and Gadd45g genes were upregulated, while Igf1, Ccl2, Hadc2, Rtn4rl1, Nfkb2, Gpr84, Pik3cg, and Abcc8 genes were downregulated in SNL rats. Compared to the SNL group, the GEG200 group and GEG600 group had increases/decreases in 16 (10/6) genes and 11 (1/10) genes, respectively. GEG downregulated Fos and Gadd45g genes and upregulated Hdac2 genes in the amygdala. In summary, GEG alleviates NP by modulating the gut microbiome and reversing a molecular neuroimmune signature.

This study examined the effects of turmeric bioactive compounds, curcumin C3 complex® (CUR) and bisdemethoxycurcumin (BDMC), on mechanical hypersensitivity and the gene expression of markers for glial activation, mitochondrial function, and oxidative stress in the spinal cord and amygdala of rats with neuropathic pain (NP). Twenty-four animals were randomly assigned to four groups: sham, spinal nerve ligation (SNL, an NP model), SNL+100 mg CUR/kg BW p.o., and SNL+50 mg BDMC/kg BW p.o. for 4 weeks. Mechanical hypersensitivity was assessed by the von Frey test (VFT) weekly. The lumbosacral section of the spinal cord and the right amygdala (central nucleus) were collected to determine the mRNA expression of genes (IBA-1, CD11b, GFAP, MFN1, DRP1, FIS1, PGC1α, PINK, Complex I, TLR4, and SOD1) utilizing qRT-PCR. Increased mechanical hypersensitivity and increased gene expression of markers for microglial activation (IBA-1 in the amygdala and CD11b in the spinal cord), astrocyte activation (GFAP in the spinal cord), mitochondrial dysfunction (PGC1α in the amygdala), and oxidative stress (TLR4 in the spinal cord and amygdala) were found in untreated SNL rats. Oral administration of CUR and BDMC significantly decreased mechanical hypersensitivity. CUR decreased CD11b and GFAP gene expression in the spinal cord. BDMC decreased IBA-1 in the spinal cord and amygdala as well as CD11b and GFAP in the spinal cord. Both CUR and BDMC reduced PGC1α gene expression in the amygdala, PINK1 gene expression in the spinal cord, and TLR4 in the spinal cord and amygdala, while they increased Complex I and SOD1 gene expression in the spinal cord. CUR and BDMC administration decreased mechanical hypersensitivity in NP by mitigating glial activation, oxidative stress, and mitochondrial dysfunction.

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. 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. 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. 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. Texas Tech University Health Sciences Center, Lubbock, TX.