Neuropathic pain: One of the potential clinical applications of NK cells
Neuropathic pain refers to pain directly caused by a certain injury or disease affecting the somatosensory system. Peripheral neuropathy causing pain may result from physical damage causing disconnection of nerve branches from their peripheral targets, or chemical neurotoxicity causing death of axons from their terminals. Axonal loss after injury is characterized by the mechanism of Wallerian degeneration, which promotes subsequent clearance of debris by immune cells. Simultaneously, a genetic program of axonal growth is permissive environment created by infiltrating immune cells. While this adaptive response to axonal injury promotes phagocytosis of debris and ultimately axonal regeneration, it also contributes to the maladaptive symptoms of neuropathic pain.
In an article in "Trends in Neurosciences", researchers pointed out that NK cells have the ability to remove damaged nerve cells that may cause pain, and may become a safe and effective treatment in the future. NK cells may target a variety of key cellular components related to neuropathic pain, playing a role through direct cytotoxicity or immunomodulation of NK cells in peripheral nerves [2]. Direct cytotoxicity is reflected in the ability of NK cells to recognize the RAE1 antigen expressed by damaged neuronal cells, thereby lysing the damaged neural cells [3]. NK cells may also help restore normal sensory function and reduce pain by eliminating misplaced sensory-innervated nerve endings. In addition, nerve cells will begin to age after nerve damage, and NK cells can play a role in clearing senescent cells and can help reduce neuropathic pain. Finally, NK cells can also regulate inflammatory responses by releasing factors, affecting the functions of dendritic cells, neutrophils and macrophages, thereby further affecting neurological recovery.
In an article in "Trends in Neurosciences", researchers pointed out that NK cells have the ability to remove damaged nerve cells that may cause pain, and may become a safe and effective treatment in the future. NK cells may target a variety of key cellular components related to neuropathic pain, playing a role through direct cytotoxicity or immunomodulation of NK cells in peripheral nerves [2]. Direct cytotoxicity is reflected in the ability of NK cells to recognize the RAE1 antigen expressed by damaged neuronal cells, thereby lysing the damaged neural cells [3]. NK cells may also help restore normal sensory function and reduce pain by eliminating misplaced sensory-innervated nerve endings. In addition, nerve cells will begin to age after nerve damage, and NK cells can play a role in clearing senescent cells and can help reduce neuropathic pain. Finally, NK cells can also regulate inflammatory responses by releasing factors, affecting the functions of dendritic cells, neutrophils and macrophages, thereby further affecting neurological recovery.
So far, preclinical research suggests that NK cells' therapeutic effects in relieving neuropathic pain may occur by removing abnormal sensory axons.What is important is that during this process, NK cells will inevitably work together with other immune cells to restore the dynamic balance of the damaged peripheral nerve microenvironment.Therapeutic immune interventions should be designed to minimize the impact of repair tissue remodeling via phagocytic and autophagic mechanisms, both of which may be equally important in preventing the chronification of pain after nerve injury.To fully realize the therapeutic potential of NK cells for peripheral neuropathy and chronic pain, several important questions regarding the distinct neuroimmune interactions between NK cells, non-neuronal cells, and sensory neurons need to be addressed.Further translational and clinical studies, as well as mechanistic studies in preclinical models, will be needed to uate whether NK cell immunotherapy is a realistic option for the treatment of neuropathic pain.
References：
[1]Lassen J, Stürner KH, Gierthmühlen J, et al. Protective role of natural killer cells in neuropathic pain conditions. Pain. 2021;162(9):2366-2375. doi:10.1097/j.pain.0000000000002274
[2]Kim HW, Wang S, Davies AJ, Oh SB. The therapeutic potential of natural killer cells in neuropathic pain. Trends Neurosci. 2023;46(8):617-627. doi:10.1016/j.tins.2023.05.008
[3]Davies AJ, Kim HW, Gonzalez-Cano R, et al. Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury. Cell. 2019;176(4):716-728.e18. doi:10.1016/j.cell.2018.12.022
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References：
[1]Lassen J, Stürner KH, Gierthmühlen J, et al. Protective role of natural killer cells in neuropathic pain conditions. Pain. 2021;162(9):2366-2375. doi:10.1097/j.pain.0000000000002274
[2]Kim HW, Wang S, Davies AJ, Oh SB. The therapeutic potential of natural killer cells in neuropathic pain. Trends Neurosci. 2023;46(8):617-627. doi:10.1016/j.tins.2023.05.008
[3]Davies AJ, Kim HW, Gonzalez-Cano R, et al. Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury. Cell. 2019;176(4):716-728.e18. doi:10.1016/j.cell.2018.12.022
Disclaimer: Shenzhen Cell Valley is committed to the research of cell and gene therapy, in order to promote emerging technologies, so that more people understand the new development of biomedicine. The content of this article is only used for information exchange, and the platform remains neutral on the content, statements and opinions of the article, and does not represent the position and views of Shenzhen Cell Valley. The relevant information in this article shall not be used for diagnosis or treatment, and cannot replace professional medical advice, and this public platform will not assume any responsibility. The final interpretation of the content of the above statement belongs to the public platform, and this statement will apply to all the articles shared on the platform at all times, thank you for your cooperation!
Copyright note: The copyright of the article belongs to Shenzhen Cell Valley, welcome individuals to forward to the circle of friends, media or institutions without authorization, reproduced in any form to other platforms, will be regarded as infringement. Reprint authorization please reply "Reprint" in the "Shenzhen Cell Valley" wechat public number to obtain reprint instructions.
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