Science: Potential mechanisms of neuropathy affecting millions of people have been discovered: nuclear transport proteins play a key role.

Neuropathic pain is pain caused by injuries or diseases that affect the body's sensory nervous system, affecting millions of people and making devastating consequences for their health.
treatments available are limited in efficacy, and the underlying mechanisms for controlling the continued existence of the disease are unclear.
August 14, 2020, Letizia Marvaldi et al. published a research paper entitled "Importin alpha 3 regulates chronic pathways in peripheral neurons" online in Science, which found that importin alpha3 (also known as karyopherin sub-alpha 4) can control the pain response of sensory neurons around mice.
the Importin alpha3 gene knockout or sensory neuron-specific knock-down in mice reduces the response to harmful stimuli and increases tolerance to neuropathy.
reducing inhibition of c-Fos or c-Jun in sensory neurons can reduce nerve pain.
drug screening found drugs that mimic the deficiency of importin alpha3.
these drugs reduce nerve pain and reduce c-Fos nuclear positioning.
therefore, interfering with c-Fos nuclear input through importin alpha 3 in peripheral neurons can promote analgesic effects.
, opioids are the most commonly used painkillers with multiple tolerance and dependence risks that can lead to considerable abuse.
the vast majority of current drug development targets in the field of pain are ion channels and neurotransmitter receptors located in the mass membrane and synapses.
importin alpha3 provides another target for molecular identity and subcellular positioning, providing opportunities for future analgesic development.
, Muhammad Saad Yousuf et al. published a review article entitled "The Importins of pain" at Science, which systematically counted the results of the study.
neuropathic pain is pain caused by injuries or diseases that affect the body's sensory nervous system, affecting millions of people and making devastating consequences for their health.
treatments available are limited in efficacy, and the underlying mechanisms for controlling the continued existence of the disease are unclear.
Importin alpha sub-family is essential for the nuclear input of ethon cells and is involved in cytoste transfer such as neurons.
despite Impportin's specific overlap, different expression lines and different cargo affinity can still be adjusted for specific functions through a single Impportin.
the study, it was found that importin alpha3 (also known as karyopherin sub-alpha 4) controlled the pain response of sensory neurons around mice.
the Importin alpha3 gene knockout or sensory neuron-specific knock-down in mice reduces the response to harmful stimuli and increases tolerance to neuropathy.
reducing inhibition of c-Fos or c-Jun in sensory neurons can reduce nerve pain.
drug screening found drugs that mimic the deficiency of importin alpha3.
these drugs reduce nerve pain and reduce c-Fos nuclear positioning.
therefore, interfering with c-Fos nuclear input through importin alpha 3 in peripheral neurons can promote analgesic effects.
in short.
the study showed that interfering with c-Fos nuclear input through importin alpha3 in sensory neurons reduced sensitivity to harmful stimuli and provided analgesic effects specifically during the maintenance phase of neuropathic pain.
direct c-Fos inhibition is effective in both the early and maintenance stages of neuropathic pain, suggesting that other forms of c-Fos nuclear input or other transcription factors may control early pain responses, while importin alpha3 is critical to later chronic pain.
the study showed that peripheral sensory neurons were the source of the effects of importin alpha3 on persistent neuropathic pain.
Between DRGs in mice and people, the expression spectrum and levels of importin alpha3 and c-Fos are conservative, and a recent study reported a significant increase in the AP1 family gene in DRG in patients with neuropathic pain, highlighting the potential of Importin alpha3 as a painkiller.
chronic pain is currently one of the most common unsusted medical needs due to the limited pain relief effects of existing drugs and adverse side effects.
addition, opioids are the most commonly used painkillers with multiple tolerance and dependence risks that can lead to considerable abuse.
the vast majority of current drug development targets in the field of pain are ion channels and neurotransmitter receptors located in the mass membrane and synapses.
importin alpha3 provides another target for molecular identity and subcellular positioning, providing opportunities for future analgesic development.
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