Vincristine increases sensation/neuropathic pain by potentiating PIEZO2
Posted: Tue Mar 26, 2024 4:39 am
from a previous article: "PIEZO2 function is needed for triggering a touch-evoked erection reflex and successful mating in both male and female mice. Humans with complete loss of PIEZO2 function have genital hyposensitivity and experience no direct pleasure from gentle touch or vibration"
on the hypothetical idea that PIEZO2 might have something to do with the hypoesthesia of PSSD, this 2023 study from China is interesting:
Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity
Full text: https://www.sciencedirect.com/science/a ... 3523001569
says that vincristine, a widely used chemotherapeutic agent for treating different cancers, often induces severe peripheral neuropathic pain / mechanical hypersensitivity in a PIEZO2 channel-dependent manner, since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity.
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.
more PIEZO2 = increased sensation of touch
less PIEZO2 = decreased sensation of touch
if a depotentiation of PIEZO2 were responsible for genital hypoesthesia in PSSD, Vincristine could increase excitability and sensations
conversely, in cases of PGAD where there is a burning and painful hyperexcitation in the genitals, a PIEZO2 inhibitor would reduce these neuropathic sensations.
but PIEZO2 is involved in myriad important things in the body if you look at the various studies and perhaps if there is a problem with PIEZO2 in PSSD it is a local one and does not involve the whole system.
could it also be involved with feelings of 'anaesthesia' to environmental stimuli underlying emotional numbness and anhedonia?
are there ways to locally potentiate and depotentiate PIEZO2, for example topically on the genitals or with targeted injections in rats?
on the hypothetical idea that PIEZO2 might have something to do with the hypoesthesia of PSSD, this 2023 study from China is interesting:
Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity
Full text: https://www.sciencedirect.com/science/a ... 3523001569
says that vincristine, a widely used chemotherapeutic agent for treating different cancers, often induces severe peripheral neuropathic pain / mechanical hypersensitivity in a PIEZO2 channel-dependent manner, since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity.
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.
more PIEZO2 = increased sensation of touch
less PIEZO2 = decreased sensation of touch
if a depotentiation of PIEZO2 were responsible for genital hypoesthesia in PSSD, Vincristine could increase excitability and sensations
conversely, in cases of PGAD where there is a burning and painful hyperexcitation in the genitals, a PIEZO2 inhibitor would reduce these neuropathic sensations.
but PIEZO2 is involved in myriad important things in the body if you look at the various studies and perhaps if there is a problem with PIEZO2 in PSSD it is a local one and does not involve the whole system.
could it also be involved with feelings of 'anaesthesia' to environmental stimuli underlying emotional numbness and anhedonia?
are there ways to locally potentiate and depotentiate PIEZO2, for example topically on the genitals or with targeted injections in rats?