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Journal Article Epublish 9 citations

PubMed: 39458557 DOI: 10.3390/nu16203563

Beneficial Effects of Ginger Root Extract on Pain Behaviors, Inflammation, and Mitochondrial Function in the Colon and Different Brain Regions of Male and Female Neuropathic Rats: A Gut-Brain Axis Study.

Nutrients 16(20)

Authors: Julianna Maria Santos, Hemalata Deshmukh, Moamen M Elmassry, Vadim Yakhnitsa, Guangchen Ji, Takaki Kiritoshi, Peyton Presto, Nico Antenucci, Xiaobo Liu, Volker Neugebauer, Chwan-Li Shen

Affiliations

  • Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Department of Microanatomy and Cellular Biology, Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
  • Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Obesity Research Institute, Texas Tech University, Lubbock, TX 79401, USA.

Abstract

BACKGROUND

Neuroinflammation and mitochondrial dysfunction have been implicated in the progression of neuropathic pain (NP) but can be mitigated by supplementation with gingerol-enriched ginger (GEG). However, the exact benefits of GEG for each sex in treating neuroinflammation and mitochondrial homeostasis in different brain regions and the colon remain to be determined.

OBJECTIVE

Evaluate the effects of GEG on emotional/affective pain and spontaneous pain behaviors, neuroinflammation, as well as mitochondria homeostasis in the amygdala, frontal cortex, hippocampus, and colon of male and female rats in the spinal nerve ligation (SNL) NP model.

METHODS

One hundred rats (fifty males and fifty females) were randomly assigned to five groups: sham + vehicle, SNL + vehicle, and SNL with three different GEG doses (200, 400, and 600 mg/kg BW) for 5 weeks. A rat grimace scale and vocalizations were used to assess spontaneous and emotional/affective pain behaviors, respectively. mRNA gene and protein expression levels for tight junction protein, neuroinflammation, mitochondria homeostasis, and oxidative stress were measured in the amygdala, frontal cortex, hippocampus, and colon using qRT-PCR and Western blot (colon).

RESULTS

GEG supplementation mitigated spontaneous pain in both male and female rats with NP while decreasing emotional/affective responses only in male NP rats. GEG supplementation increased intestinal integrity (claudin 3) and suppressed neuroinflammation [glial activation (GFAP, CD11b, IBA1) and inflammation (TNFα, NFκB, IL1β)] in the selected brain regions and colon of male and female NP rats. GEG supplementation improved mitochondrial homeostasis [increased biogenesis (TFAM, PGC1α), increased fission (FIS, DRP1), decreased fusion (MFN2, MFN1) and mitophagy (PINK1), and increased Complex III] in the selected brain regions and colon in both sexes. Some GEG dose-response effects in gene expression were observed in NP rats of both sexes.

CONCLUSIONS

GEG supplementation decreased emotional/affective pain behaviors of males and females via improving gut integrity, suppressing neuroinflammation, and improving mitochondrial homeostasis in the amygdala, frontal cortex, hippocampus, and colon in both male and female SNL rats in an NP model, implicating the gut-brain axis in NP. Sex differences observed in the vocalizations assay may suggest different mechanisms of evoked NP responses in females.

MeSH

Hippocampus, Genes, Frontal Lobe, Pain, Homeostasis, Brain, Mitochondria, Colon, Central Nervous System, Food, Amygdala, Sex, Pharmaceutical Vehicles

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