(P25-035-24) Effects of Ginger Supplementation on Neuroinflammation and Mitochondrial Function in Spinal Cords of Rats With Neuropathic Pain: Evidence for Sex Differences

Objectives: Neuroinflammation and mitochondrial dysfunction in the spinal cord play key roles in the development of neuropathic pain (NP). We examined and compared the effects of 3 different gingerol-enriched ginger (GEG) doses on nocifensive reflexes and neuroinflammation- and mitochondria-related gene expression in the spinal cord of male and female rats with NP.

Methods: 37 male and 33 female SD rats were assigned to 5 groups: control group (sham surgery and corn oil, p.o.), SNL group (spinal nerve ligation surgery and corn oil, p.o.), and SNL with 3 different GEG doses (SNL+200mg/kg GEG, SNL+400mg/kg GEG, and SNL+600mg/kg GEG, p.o.) for 4 weeks. Nocifensive reflexes evoked by paw compression were assessed prior to surgery (baseline) and at the end of the study. The spinal cord (L4-L5) was harvested for the analysis of mRNA expression of markers related to mitochondrial function and neuroinflammation. Data were analyzed by one-way ANOVA with post hoc Tukey’s test for the male and female cohort, respectively.

Results: GEG supplementation mitigated SNL-induced decreased nocifensive reflex thresholds in both male and female NP rats, regardless of GEG doses. GEG supplementation led to lower gene expression levels of markers for neuroinflammation [CD11b (male), TNF-α (male), IL-1b (male, female)], glial activation [microglia, IBA-1 (male), astrocytes, GFAP (female)], mitochondrial fission [DRP1 (male, female)], mitochondrial fusion [MFN1 (male), MFN2 (male)], mitochondrial biosynthesis [PGC1α (male)] and mitophagy [PINK1 (male)]. GEG supplementation increased gene expression levels of mitochondrial fission adaptor [FIS1 (male)], mitochondrial transcription factor [TFAM (male)], and antioxidant factors [NRF1 (male, female), Complex I (male, female)] in the spinal cord of NP rats. Compared to GEG’s effect in male NP rats, GEG exhibited opposite trends on MFN1, MFN2, and PGC1α in the spinal cord of female NP rats.

Conclusions: GEG mitigates SNL-induced pain hypersensitivity in male and female rats, in part, via reducing neuroinflammation, improving mitochondrial function, and increasing antioxidant/anti-oxidative stress capacity in the spinal cord. However, the underlying molecular mechanisms appear to be sex specific.

Funding Sources: USDA-NIFA grant 2021-67017-34026 and NIH grant R01NS038261