Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity
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 mechanic...
Gespeichert in:
| Hauptverfasser: | , , , , , , |
|---|---|
| Format: | Buch |
| Veröffentlicht: |
Elsevier,
2023-08-01T00:00:00Z.
|
| Schlagworte: | |
| Online-Zugang: | Connect to this object online. |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Zusammenfassung: | 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 vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity. |
|---|---|
| Beschreibung: | 2211-3835 10.1016/j.apsb.2023.05.010 |