Background & Aims

Neuroinflammation plays a key role in the development of neuropathic pain (NP) (Sommer 2018). The relationship between a “leaky gut” and NP has received increased attention (Shen 2022, Ruga 2023). We previously reported gingerol-enriched ginger (GEG) supplementation into the diet mitigated pain and decreased intestinal permeability in male rats with NP (Shen 2022). However, the comparisons between male and female NP rats treated with different doses of GEG on outcome measures such as spontaneous pain, leaky gut, fecal metabolites, and gene expression markers of neuroinflammation are lacking. This study was designed to address this knowledge gap and investigate the effects of 3 different doses of GEG on spontaneous pain, intestinal permeability, fecal metabolites, and mRNA levels of molecules related to neuroinflammation in the dorsal root ganglion (DRG) and colon in the spinal nerve ligation (SNL) model of NP.

Methods

Neuroinflammation plays a key role in the development of neuropathic pain (NP) (Sommer 2018). The relationship between a “leaky gut” and NP has received increased attention (Shen 2022, Ruga 2023). We previously reported gingerol-enriched ginger (GEG) supplementation into the diet mitigated pain and decreased intestinal permeability in male rats with NP (Shen 2022). However, the comparisons between male and female NP rats treated with different doses of GEG on outcome measures such as spontaneous pain, leaky gut, fecal metabolites, and gene expression markers of neuroinflammation are lacking. This study was designed to address this knowledge gap and investigate the effects of 3 different doses of GEG on spontaneous pain, intestinal permeability, fecal metabolites, and mRNA levels of molecules related to neuroinflammation in the dorsal root ganglion (DRG) and colon in the spinal nerve ligation (SNL) model of NP.

Results

37 male and 33 female Sprague-Dawley rats were assigned to 5 groups: a control group (Sham surgery and vehicle: corn oil, p.o.), an SNL group (SNL surgery and vehicle: corn oil, p.o.), and SNL groups with 3 varying GEG doses [SNL+200mg/kg GEG, SNL+400mg/kg GEG, and SNL+600mg/kg GEG, p.o.] given post-surgery for 4 weeks. The levels of spontaneous pain were assessed by Rodent Grimace Test (RGT) scoring prior to surgery (baseline) and at the end of study (4 weeks of GEG or vehicle treatment). At the end of study, intestinal permeability was evaluated with plasma lipopolysaccharide binding protein (LBP) concentrations using ELISA. Gene expression levels of neuroinflammation markers were measured in the DRG (L5, level of SNL) and colon using qRT-PCR. Protein expression levels in the colon were determined using western blotting. Fecal negative and positive hydrophilic metabolites were measured using LC-MS/MS analysis. Data was analyzed by one-way ANOVA, and followed-up by post hoc Tukey’s te

Conclusions

GEG mitigates spontaneous pain responses in both male and female rats with NP, in part, via improved intestinal integrity, modulated fecal metabolites/pathways, and decreased neuroinflammatory gene expression in the DRG and colon.

References

•Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. 2018 Mar;159(3):595-602. doi: 10.1097/j.pain.0000000000001122.
•Shen CL, Wang R, Yakhnitsa V, Santos JM, Watson C, Kiritoshi T, Ji G, Hamood AN, Neugebauer V. Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection. Front Pharmacol. 2022 Jul 8;13:912609. doi: 10.3389/fphar.2022.912609.
•Ruga S, Galla R, Ferrari S, Invernizzi M, Uberti F. Novel Approach to the Treatment of Neuropathic Pain Using a Combination with Palmitoylethanolamide and Equisetum arvense L. in an In Vitro Study. Int J Mol Sci. 2023 Mar 13;24(6):5503. doi: 10.3390/ijms24065503.

Presenting Author

Chwan-Li Shen

Poster Authors

Chwan-Li Shen

PhD

Texas Tech University Health Sciences Center

Lead Author

E-mail

Julianna Santos PhD

Texas Tech University Health Sciences Center

Lead Author

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Hemalata Deshmukh PhD

Texas Tech University Health Sciences Center

Lead Author

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Moamen Elmassry PhD

Princeton University

Lead Author

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Fang Chen PhD

Texas Tech University

Lead Author

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Peyton Presto

Texas Tech University Health Sciences Center

Lead Author

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Jacob Lovett

Texas Tech University Health Sciences Center

Lead Author

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Volker Neugebauer PhD

Texas Tech University Health Sciences Center

Lead Author

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Topics

  • Models: Chronic Pain - Neuropathic