Background: Emerging evidence suggests short-chain fatty acids (SCFA) play a key role in the pathogenesis of neuropathic pain by regulating tight junction integrity and microglial activation: a gut-brain-interaction. We previously reported gingerol-enriched ginger (GEG) improves GI health in diabetic rats (Wang et al. 2022) and reduced mechanosensitivity in rats with spinal nerval ligation (SNL, a model of neuropathic pain) (Shen et al. 2022). In this study, we further evaluated the effects of three dosages of GEG on spontaneous pain sensitivity, fecal SCFA, tight junction integrity, and microglial activation in SNL rats.
Objective: . To evaluate the effects of three dosages of GEG on spontaneous pain sensitivity, fecal SCFA, tight junction integrity, and microglial activation in SNL rats.
Methods: 36 male rats were divided into: Sham, SNL, SNL+200mg GEG/kg BW, p.o. (GEG200), SNL+400mg GEG/kg BW, p.o. (GEG400), and SNL+600mg GEG/kg BW, p.o. (GEG600) groups for 4 weeks. Spontaneous pain was assessed with the Rat Grimace Scale (RGS). Cecal-feces samples were collected for SCFA analysis using LC-MS. mRNA gene expression levels of tight junction integrity and mitochondrial function in colon and amygdala were determined using qRT-PCR. Data was analyzed statistically.
Results: GEG supplementation for 4 weeks significantly mitigated SNL-induced spontaneous pain, evidenced in significantly altered nose bulge, ear position, whisker change, and overall score in the RGS. Compared to the Sham rats, the SNL rats had greater concentrations of fecal SCFA, i.e., acetic acid and propanoic acid. Supplementation of GEG to the SNL rats significantly reduced the SCFA concentrations in feces (P<0.05). GEG supplementation improved tight junction integrity of gut and brain, as shown by increased claudin-3 mRNA expression in both the colon and amygdala of SNL rats (P<0.05). Furthermore, supplementation of GEG attenuated SNL-induced mRNA expression levels of microglia activation markers, namely CD11b, IBA-1, and GFAP, in the colon and amygdala of rats (P<0.05). There were no significant differences in the measured parameters between three GEG dosages.
Conclusions: This study suggests that ginger supplementation mitigates spontaneous pain in a rat neuropathic pain model, via decreasing fecal SCFA, improving tight junction integrity, and reducing glia activation.
