(P03-071-23) Ginger Differentially Mitigates Neuroinflammation and Improves Mitochondrial Function in Male and Female Rats With Neuropathic Pain: Gut-Brain Axis

Objectives: Evaluate the effects of GEG on hypersensitivity, neuroinflammation, and mitochondria function in the amygdala and colon of female and male rats with neurophatic pain (NP)

Methods: 37 male and 33 female Sprague-Dawley rats were assigned to 5 groups: control (SHam surgery+vehicle), SNL+vehicle, and SNL with 3 different GEG doses (SNL+200mg/Kg GEG, SNL+400mg/Kg GEG, and SNL+600mg/Kg) for 5 weeks. To assess NP, the mechanical paw withdrawal reflex threshold was measured. RNA was extracted from the colon and right amygdala (AMR) followed by cDNA conversion and qRT-PCR to evaluate the genes expression involved in neuroinflammation (NF-kB and TNFα), and mitochondria function (MFN2, FIS1, PGC1α, Complex I, and Complex III). All statistical comparison was done using one-way ANOVA with post hoc Tukey's test.

Results: Male SNL rats showed a decrease in reflex thresholds after 5 weeks. The female SNL rats only showed a trend for hypersensitivity, suggesting that female SNL rats are more resistant to pain compared to male rats. In male rats, 600GEG increased the reflex thresholds, indicating less hypersensitivity while the lower doses of GEG200 and GEG400 showed only a trend towards increased reflex thresholds. In female SNL rats, GEG400 increased the reflex thresholds. In both male and female SNL rats, the levels of NF-kB and TNFα in the colon and AMR were increased, while GEG supplementation suppressed those. GEG significantly decreased mRNA expression levels of MFN2 in the AMR and colon of male SNL rats, while GEG400 and GEG600 increased MFN2 mRNA expression in the colon of female SNL rats. GEG200 increased the mRNA expression of FIS1 in the colon of male SNL rats, but GEG400 and GEG600 decreased FIS1 in the colon of female SNL rats. GEG supplementation increased the mRNA expression level of PGC1α in the colon and AMR of both sexes. GEG also upregulated the mRNA expression levels of mitochondrial Complex I and III in both tissues and sexes.

Conclusions: This study suggests that GEG supplementation reduced pain behaviors and inflammation and restored mitochondria function in the SNL rat model of NP.

Funding Sources: This study was supported by USDA-NIFA 2021-67017-34026.