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Guided reading
Guided readingMore than 300 million people in China suffer from chronic pain
.
Drug therapy is one of the main measures for clinical pain relief
More than 300 million people in China suffer from chronic pain
However, the above common analgesics have different degrees of side effects in the digestive tract, cardiovascular, nervous system, etc.
A recent study in Cell Research revealed a new target for the treatment of chronic pain
01
01 01Hv1 may have new neurobiological functions
Hv1 or has a new neurobiological functionHv1 or has a new neurobiological functionHv1 belongs to the superfamily of voltage-gated ion channels and is one of the simplest voltage-gated ion channels
.
In the mammalian nervous system, Hv1 is the only proton-selective ion channel
The research team found that Hv1 was expressed in mouse dorsal root ganglion (DRG) neurons, and that Hv1 expression was significantly up-regulated after acute and chronic inflammatory stimulation or neuronal hyperexcitability
.
Expression of Hv1 was also found in human skin nerve endings
.
This finding suggests that Hv1 may have a new neurobiological function
Ion channel-like proteins are very lacking in selective pharmacological tools
.
The Hv1 channel system is small, and the development of inhibitors faces additional difficulties
Yang Huaiyu's team has revealed that targeting the intermediate state of ion channels can be used to discover inhibitors
.
Drawing on this non-classical regulation strategy, in this study, the research team designed an inhibitor YHV98-4 targeting the dynamic intermediate state of Hv1 channel
Using a novel inhibitor, Hv1KO mice, and an AAV virus-mediated strategy for specific knockdown of Hv1 on dorsal root ganglion sensory neurons, we isolated, characterized, and evaluated Hv1-mediated effects on DRG neurons under normal and inflammatory conditions.
We found that Hv1-mediated proton currents were significantly up-regulated in inflammatory states or neuropathic pain states
.
Next, the proton imaging technique revealed that Hv1 plays an important role in the maintenance of proton homeostasis in DRG neurons: inhibition of Hv1 was found to alleviate the intracellular pH alkalinization of sensory neurons in the lower dorsal root ganglia of chronic pain, thereby inhibiting NOX-dependent ROS generation
.
02
02 02Inhibition of Hv1 is effective in relieving pathological pain Title
Inhibition of Hv1 is effective in relieving pathological pain Title Inhibiting Hv1 is effective in relieving pathological pain TitleIn order to further verify that Hv1 is involved in the development of chronic inflammation and pain, in animal-level experiments, the authors combined pharmacology, Hv1 gene knockout and Hv1-specific knockdown in DRG neurons, and found that inhibiting Hv1 can effectively relieve pathological pain.
Improve inflammatory conditions
.
Next, the authors used pharmacological inhibition and Hv1 knockdown in DRG neurons, and found that inhibition of Hv1 can indeed effectively alleviate the side effects of morphine use and reduce ROS production
.
In short, this study is the first to report a novel function of Hv1 in a new cell type in the nervous system and to develop the first Hv1 inhibitors with good selectivity and potential for in vivo applications
.
Elsewhere, the researchers revealed that Hv1 may be a potential new target for chronic pain treatment and amelioration of morphine-induced adverse effects
Original source:
Original source:Zhang, Q.
Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects
