Follistatin drives neuropathic pain in mice through IGF1R signaling in nociceptive neurons
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Le résumé fourni par la source
Neuropathic pain is a debilitating chronic condition that lacks effective treatment. The role of cytokine- and chemokine-mediated neuroinflammation in its pathogenesis has been well documented. Follistatin (FST) is a secreted protein known to antagonize the biological activity of cytokines in the transforming growth factor-β (TGF-β) superfamily. The involvement of FST in neuropathic pain and the underlying mechanism remain largely unknown. Here, we report that FST was up-regulated in A-fiber sensory neurons after spinal nerve ligation (SNL) in mice. Inhibition or deletion of FST alleviated neuropathic pain and reduced the nociceptive neuron hyperexcitability induced by SNL. Conversely, intrathecal or intraplantar injection of recombinant FST, or overexpression of FST in the dorsal root ganglion (DRG) neurons, induced pain hypersensitivity. Furthermore, exogenous FST increased neuronal excitability in nociceptive neurons. The biolayer interferometry (BLI) assay and coimmunoprecipitation (co-IP) demonstrated direct binding of FST to the insulin-like growth factor-1 receptor (IGF1R), and IGF1R inhibition reduced FST-induced activation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), as well as neuronal hyperexcitability. Further co-IP analysis revealed that the N-terminal domain of FST exhibits the highest affinity for IGF1R, and blocking this interaction with a peptide derived from FST attenuated Nav1.7-mediated neuronal hyperexcitability and neuropathic pain after SNL. In addition, FST enhanced neuronal excitability in human DRG neurons through IGF1R. Collectively, our findings suggest that FST, released from A-fiber neurons, enhances Nav1.7-mediated hyperexcitability of nociceptive neurons by binding to IGF1R, making it a potential target for neuropathic pain treatment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Follistatin drives neuropathic pain in mice through IGF1R signaling in nociceptive neurons
- Date Crossref
- 16/10/2024
- Éditeur
- American Association for the Advancement of Science (AAAS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Nantong University Institute of Pain Medicine and Special Environmental Medicine pays non établi dans la noticeUniversité ou école supérieure
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Affiliated Hospital of Nantong University pays non établi dans la noticeÉtablissement de santé
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Pain Management Institute pays non établi dans la noticeÉtablissement de santé
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Duke University Departments of Anesthesiology pays non établi dans la noticeUniversité ou école supérieure
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University of North Carolina at Chapel Hill Department of Psychology pays non établi dans la noticeUniversité ou école supérieure
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Anyang Hospital of Traditional Chinese Medicine pays non établi dans la noticeÉtablissement de santé
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Mayo Clinic Department of Neurology pays non établi dans la noticeÉtablissement de santé
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WinnMed pays non établi dans la noticeOrganisation à but non lucratif
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Huazhong University of Science and Technology Union Shenzhen Hospital Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine pays non établi dans la noticeUniversité ou école supérieure
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Nantong Hospital of Traditional Chinese Medicine Department of Pain Management pays non établi dans la noticeÉtablissement de santé
Institute of Pain Medicine and Special Environmental Medicine — Nantong University, Affiliated Hospital of Nantong University et Pain Management Institute, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.