Dietary Supplementation of Gingerols- and Shogaols-Enriched Ginger Root Extracts Attenuate Pain-Associated Behaviors in Animals with Spinal Nerve Ligation

Abstract

Abstract Objectives Neuropathic pain (NP), arising from damage to the nervous system, could be a consequence of the imbalance between reactive oxygen species (ROS) and endogenous antioxidants after nerve injury, leading to neuroinflammation. Therefore, this study was to evaluate the effects of two ginger root extracts rich in gingerols and shogoals, respectively, on pain sensitivity and anxiety-like behaviors in neuropathic animals. We also assessed the plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) damage, a biomarker of excessive mitochondria-derived ROS linked to inflammation. Methods Sixteen male rats were randomly divided into 4 groups: sham group, spinal nerve ligation (SNL) group as the pain control group, SNL+ gingerols-enriched ginger (GEG) extract group, and SNL+ shogoals-enriched ginger (SEG) extract group. Animals in GEG and SEG groups were fed with their respective diets on the day of SNL surgery for 30 days. At 1 day before and 10, 20, and 30 days post operation, (i) paw withdrawal mechanical thresholds were measured using von Frey filaments for pain sensory assessment; and (ii) center frequency and center duration in the open field test (OFT) were measured to assess anxiety-like behavior. At Day 30, plasma was obtained for ccf-mtDNA concentration measurement. Data were analyzed by one-way ANOVA or one-way repeated measures analysis of variance follow by post-hoc analysis. Results Compared to the sham group, the SNL group had significant greater pain sensitivity to mechanical stimuli. When compared to the SNL group, both GEG and SEG groups showed significantly (50%) reduced pain sensitivity (increased thresholds) as early as at 10 days and sustained at 30 days. Relative to the SNL group, both GEG and SEG groups also had less anxiety-like behavior (as indicated by the elongated center duration and increased center frequency in OFT). The SNL group had significantly higher plasma ccf-mtDNA levels relative to the sham group. When SNL-animals were fed a diet supplemented with either gingerols or shogaols, both groups showed reduction in plasma ccf-mtDNA. Conclusions Both gingerols and shogaols supplementation decreased pain sensitivity and improved anxiety-like behavior mediated in part through the suppression of mitochondrial damage. Funding Sources Texas Tech University Health Sciences Center.