Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection

Abstract

Objectives: Emerging evidence suggests an important role of the gut-brain axis in the development of neuropathic pain (NP). We investigated the effects of gingerol-enriched ginger (GEG) on pain behaviors, as well as mRNA expressions of inflammation via tight junction proteins in GI tissues (colon) and brain tissues (amygdala, both left and right) in animals with NP.Methods: Seventeen male rats were randomly divided into three groups: Sham, spinal nerve ligation (SNL, pain model), and SNL+0.375% GEG (wt/wt in diet) for 4 weeks. Mechanosensitivity was assessed by von Frey filament tests and hindpaw compression tests. Emotional responsiveness was measured from evoked audible and ultrasonic vocalizations. Ongoing spontaneous pain was measured in rodent grimace tests. Intestinal permeability was assessed by the lactulose/D-mannitol ratio in urine. The mRNA expression levels of neuroinflammation (NF-κB, TNF-α) in the colon and amygdala (right and left) were determined by qRT-PCR. Data was analyzed statistically.Results: Compared to the sham group, the SNL group had significantly greater mechanosensitivity (von Frey and compression tests), emotional responsiveness (audible and ultrasonic vocalizations to innocuous and noxious mechanical stimuli), and spontaneous pain (rodent grimace tests). GEG supplementation significantly reduced mechanosensitivity, emotional responses, and spontaneous pain measures in SNL rats. GEG supplementation also tended to decrease SNL-induced intestinal permeability markers. The SNL group had increased mRNA expression of NF-κB and TNF-α in the right amygdala and colon; GEG supplementation mitigated these changes in SNL-treated rats.Conclusion: This study suggests GEG supplementation palliated a variety of pain spectrum behaviors in a preclinical NP animal model. GEG also decreased SNL-induced intestinal permeability and neuroinflammation, which may explain the behavioral effects of GEG.

Essential Oil Constituents as Anti-Inflammatory and Neuroprotective Agents: An Insight through Microglia Modulation

“…EOs may also impact neuroinflammation through the gut-brain axis [38]. Studies suggest that EOs modulate intestinal permeability and gut microbiota, potentially indirectly influencing microglia-related function by improving gut health and reducing gut-derived inflammation.…”

Ginger Polyphenols Reverse Molecular Signature of Amygdala Neuroimmune Signaling and Modulate Microbiome in Male Rats with Neuropathic Pain: Evidence for Microbiota–Gut–Brain Axis

“…Our previous work linked ginger's anti-inflammatory and antioxidant properties to antinociception [17,18]. Single-dosage gingerol-enriched ginger (GEG) dietary supplementation significantly mitigated mechanical hypersensitivity in rats with spinal nerve ligation (SNL)-induced NP via, in part, (i) modulation of the gut microbiota and metabolites [17] and (ii) suppression of mRNA NF-κB and TNF-α expression in the amygdala and colon [18]. Here, we explored the effects of GEG on neuroimmune signaling with a focus on the amygdala for the following reasons.…”

“…Neuroplasticity in the amygdala has been linked to pain behaviors. While most research on underlying mechanisms has focused on neuronal mechanisms such as synaptic plasticity and hyperexcitability, recent evidence suggests that neuroimmune signaling contributes to pain mechanisms in the amygdala [18,21]. Finally, the amygdala has been recognized as a key region and hub for brain-gut interactions [22,23].…”

“…In addition, we also conducted pain assessment and gut microbiome analysis in the cecal feces of the animals. Different from previous studies where GEG was delivered via diet at a single dosage [17,18], in the present study, GEG was given via oral gavage at two dosages (200 mg/kg and 600 mg/kg body weight daily) to evaluate if there was any response in the outcome parameters, namely, mechanical hypersensitivity, gut microbiome composition, and neuroinflammation signature gene expression.…”

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function

“…Emerging evidence shows dietary bioactive compounds modulate gut health, intestinal barrier function [ 9 , 10 ], and mitochondrial activity, representing a novel option to modulate energy expenditure and energetic metabolism in cells and tissues [ 5 , 11 ]. Gingerol-enriched-ginger (GEG) with antioxidant and anti-inflammatory properties has been reported to improve glucose metabolism and enhance insulin sensitivity in diabetic animals [ 12 , 13 , 14 , 15 ].…”