ArticleFrontiers in pharmacology2018
Role of Keap1-Nrf2 Signaling in Anhedonia Symptoms in a Rat Model of Chronic Neuropathic Pain: Improvement With Sulforaphane.
Article in Frontiers in pharmacology, 2018. 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, 37 citations in OpenAlex.
- Nitroxidative Stress, Cell-Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain.International journal of molecular sciences · 2025Review
- Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia.Anesthesia and analgesia · 2024Article
- Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling.Journal of translational medicine · 2023Article
- The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain.Antioxidants (Basel, Switzerland) · 2022Review
- Biological mechanisms and clinical efficacy of sulforaphane for mental disorders.General psychiatry · 2022Review
- Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation.Experimental and therapeutic medicine · 2021Article
- Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents.Translational psychiatry · 2021Article
- Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.The international journal of neuropsychopharmacology · 2021Article
- Evaluation of Molecular and Cellular Alterations Induced by Neuropathic Pain in Rat Brain Glial cells.Iranian journal of pharmaceutical research : IJPR · 2021Article
- OCT4 Represses Inflammation and Cell Injury During Orchitis by Regulating CIP2A Expression.Frontiers in cell and developmental biology · 2021Article
- Dexmedetomidine Relieves Neuropathic Pain in Rats With Chronic Constriction Injury via the Keap1-Nrf2 Pathway.Frontiers in cell and developmental biology · 2021Article
- Article
- Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling.Anesthesiology · 2020Article
- Analgesic and Antidepressant Effects of Oltipraz on Neuropathic Pain in Mice by Modulating Microglial Activation.Journal of clinical medicine · 2019Article
- Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain.Translational psychiatry · 2019Article
- Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling.Frontiers in pharmacology · 2019Article
- Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages.Frontiers in pharmacology · 2018Review
- Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective.Frontiers in pharmacology · 2018Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
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Abstract
Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia (loss of pleasure), which is a core clinical manifestation of depression. Accumulating studies have shown the beneficial effects of the natural compound sulforaphane (SFN), an activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), on depression-like phenotype through a potent anti-inflammatory effect. However, it is unknown whether SFN confers beneficial effects in neuropathic pain-associated anhedonia. Spared nerve injury (SNI) is classical rodent model of chronic neuropathic pain. We here used a rat model of SNI. Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without an anhedonia phenotype. Nrf2 protein expression was significantly decreased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, and skeletal muscle, but not in the nucleus accumbens, in anhedonia-susceptible rats compared with sham or anhedonia-resistant rats. The expression of Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1), a partner of Nrf2, in mPFC, hippocampus, and muscle of anhedonia-susceptible rats was also significantly lower than that in sham or anhedonia-resilient rats. Subsequent SFN administration after SNI surgery exerted therapeutic effects on reduced mechanical withdrawal threshold (MWT) scores, but not on sucrose preference, through the normalization of Keap1-Nrf2 signaling in the spinal cords of anhedonia-susceptible rats. Interestingly, treatment with SFN 30 min prior to SNI surgery significantly attenuated reduced MWT scores and sucrose preference, and restored tissue Keap1 and Nrf2 levels. In conclusion, this study suggests that decreased Keap1-Nrf2 signaling in mPFC, hippocampus, and muscle may contribute to anhedonia susceptibility post-SNI surgery, and that SFN exerts beneficial effects in SNI rats by normalization of decreased Keap1-Nrf2 signaling.
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