Science: Indispensable!

Click on the blue word to focus on our noxious stimuli that activate the Aδ and C fibers of nociceptors, and subsequent transmission of excitatory information through these fibers to the dorsal horn of the spinal cord (SDH) activates nociceptive projection neurons in this area
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Neuropathic pain from peripheral nerve injury is persistent, even if the cause of the injury goes away
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Previous studies have shown that after peripheral nerve injury, the number of microglia in the SDH area increases, the morphology changes to an activated state, and inflammatory factors are released
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Integrin αX (Itgax), also known as CD11c, is a subunit of complement protein C3 receptor 4, which binds to β 2 chain to form leukocyte-specific integrin, which can be used as a marker for dendritic cells
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The number of CD11c-positive microglia is increased in Alzheimer's disease and multiple sclerosis
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On April 1, 2022, the research team of Makoto Tsuda of Kyushu University in Japan revealed that CD11c-positive microglia are a key factor in the self-healing and recurrence of neuropathic pain
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Figure 1: The number of CD11c-positive microglia increases after injury.
The Itgax-cre mouse tool found that the number of CD11c-positive microglia in the SDH region was low in normal physiological conditions, but this number increased sharply after peripheral nerve injury.
It peaked on the 14th day after injury and then gradually decreased until it remained high until 2 months after injury
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However, no increase in the number of CD11c-positive microglia was observed in the inflammatory pain model
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Under normal circumstances, the paw withdrawal threshold of mice gradually began to increase after 2 weeks of peripheral nerve injury, which was a process of natural recovery in pain hypersensitivity
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However, after specifically inducing the death of CD11c-positive microglia in the SDH region by diphtheria toxin, the above-mentioned self-healing process could not be performed until one and a half months, which indicated that CD11c-positive microglia played a key role in the process of pain relief
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Figure 2: Specific knockout of Igf1 in CD11c-positive microglia inhibits the process of pain self-healing Further molecular experiments showed that Igf1 expression in CD11c-positive microglia increased after peripheral nerve injury, reaching a peak at 5 weeks after injury
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Mice with specific knockout of CD11c-positive microglia Igf1 by the tool or intramyelin injection of anti-Igf1 antibody were also unable to self-heal from pain
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The tyrosine kinase receptor AXL has been implicated in the phagocytosis of myelin debris
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Immunofluorescence experiments and immunoelectron microscopy experiments found that CD11c-positive microglia phagocytosed myelin, and this phagocytosis was enhanced after peripheral nerve injury, and the level of AXL protein increased
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AXL knockout can further aggravate the decrease in Igf1 expression caused by peripheral nerve damage, and at the same time, the pain self-healing process in mice is also hindered
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Figure 3: Depletion of microglia causes pain recurrence Either specific knockout of Igf1 on microglia or intramyelin injection of anti-Igf1 antibodies can re-evoke pain responses that persist for longer periods of time
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Overall, this paper found that changes in the number of CD11c-positive microglia caused by peripheral nerve injury are crucial for subsequent pain self-healing and recurrence, which provides new research ideas for the treatment of pain diseases
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【Reference】1.
A spinal microglia population involved in remitting and relapsing neuropathic pain The pictures in the text are from the reference