神経成長因子により引き起こされる痛覚過敏とそのメカニズム

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  • Thermal ⁄ mechanical hyperalgesia induced by nerve growth factor and their mechanisms

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<p>We focus in the present review on the molecular mechanisms for nerve growth factor (NGF) to induce thermal ⁄ mechanical hyperalgesia. Transient receptor potential vanilloid 1 (TRPV1) is pivotal to sensitize nociceptor to heat after NGF administration. Acceleration of membrane trafficking of TRPV1 through protein kinase C pathway without increase in gene expression contributes acute thermal hyperalgesia. Signaling endosome of NGF–receptor tyrosine kinase A (TrkA) complex is transported from periph­eral axonal terminal to the cell body and activate transcription factors. This transcriptional activation causes upregulation of some sodium channels, neuropeptides and acid–sensing ion channels to induce long–lasting sensitization to heat. Histamine and serotonin released from activated mast cells and neutrophils by NGF also indirectly contribute to inducing thermal hyperalgesia.</p><p>NGF also causes mechanical hyperalgesia in not only animals but also human. Repetitive administration of NGF induces long–lasting and wide–spreading mechanical hyperalgesia, that is reduced by TrkA signaling pathway inhibition. Recent report demonstrates NGF and Piezo2 are involved in mechanical sensitization of the silent nocicep­tor. However, mechanism of mechanical sensitization by NGF is still unclear, as mechanical transducer channels are not fully identified in other nociceptors. We hope molecular mechanism in NGF–induced hyperalgesia will be clarified in the future.</p>

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  • PAIN RESEARCH

    PAIN RESEARCH 37 (3), 131-140, 2022-10-20

    日本疼痛学会

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