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Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity 被引量:1
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作者 mingli duan Yurui Jia +4 位作者 Lifang Huo Yiting Gao Jia Wang Wei Zhang Zhanfeng Jia 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第8期3365-3381,共17页
Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodyn... Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia.However,mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood.In the present study,we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity.Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting(RA)mechanically-activated(MA)currents in rat dorsal root ganglion(DRG)neurons.We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension(SPMT)of these cells following vincristine treatment.Reducing SPMT of DRG neurons by cytochalasin D(CD),a disruptor of the actin filament,abolishes vincristine-induced potentiation of PIEZO2 MA currents,and suppresses vincristine-induced mechanical hypersensitivity in rats.Collectively,enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristineinduced mechanical allodynia and hyperalgesia in rats.Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity. 展开更多
关键词 VINCRISTINE Peripheral neuropathic pain Mechanical hypersensitivity Dorsal root ganglion neurons PIEZO2mechanically-activated currents
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