ArticleCNS neuroscience & therapeutics2023
Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain.
Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Effects ofFoods (Basel, Switzerland) · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Electroacupuncture Attenuates Cyclophosphamide-Induced Bladder Pain by Restoring Autophagy in Spinal Inhibitory Interneurons.ACS omega · 2026Article
- Farnesoid X receptor deficiency accelerates aging and systemic functional decline in male mice.Biogerontology · 2026Article
- Hyodeoxycholic acid relieves neuropathic pain by activating farnesoid X receptor signaling.Journal of advanced research · 2026Article
- Article
- Targeting the Gut Microbiota: Mechanistic Investigation of Polyphenol Modulation of the Gut-Brain Axis in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- The liver-brain axis, from its function to preventive therapeutic strategies in diseases.Frontiers in endocrinology · 2026Review
- The bridging role of gut microbiota-derived metabolites in neuropathic pain comorbid with anxiety.Frontiers in neuroscience · 2026Review
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- TRPC4 Mediates Trigeminal Neuropathic Pain via CaCNS neuroscience & therapeutics · 2025Article
- Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy.Nutrients · 2025Article
- Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways.Current issues in molecular biology · 2025Review
- Spinal astrocytes involved in the pathogenesis and treatment of neuropathic pain.Frontiers in cellular neuroscience · 2025Review
- Gut-Spinal Cord Axis in Spinal Cord Injury: Bidirectional Inflammatory Mechanisms and Microbiota-Targeted Therapeutic Strategies.Journal of inflammation research · 2025Review
- Emerging Roles of Bile Acids and TGR5 in the Central Nervous System: Molecular Functions and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.Biomolecules & therapeutics · 2024Review
- Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain.CNS neuroscience & therapeutics · 2023Article
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
aimsBeyond digestion, bile acids have been recognized as signaling molecules with broad paracrine and endocrine functions by activating plasma membrane receptor (Takeda G protein-coupled receptor 5, TGR5) and the nuclear farnesoid X receptor (FXR). The present study investigated the role of bile acids in alleviating neuropathic pain by activating TGR5 and FXR.
methodNeuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. TGR5 or FXR agonist was injected intrathecally. Pain hypersensitivity was measured with Von Frey test. The amount of bile acids was detected using a bile acid assay kit. Western blotting and immunohistochemistry were used to assess molecular changes.
resultsWe found that bile acids were downregulated, whereas the expression of cytochrome P450 cholesterol 7ahydroxylase (CYP7A1), a rate-limiting enzyme for bile acid synthesis, was upregulated exclusively in microglia in the spinal dorsal horn after SNI. Furthermore, the expression of the bile acid receptors TGR5 and FXR was increased in glial cells and GABAergic neurons in the spinal dorsal horn on day 7 after SNI. Intrathecal injection of either TGR5 or FXR agonist on day 7 after SNI alleviated the established mechanical allodynia in mice, and the effects were blocked by TGR5 or FXR antagonist. Bile acid receptor agonists inhibited the activation of glial cells and ERK pathway in the spinal dorsal horn. All of the above effects of TGR5 or FXR agonists on mechanical allodynia, on the activation of glial cells, and on ERK pathway were abolished by intrathecal injection of the GABA
conclusionThese results suggest that activation of TGR5 or FXR counteracts mechanical allodynia. The effect was mediated by potentiating function of GABA
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