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Click on the blue letters to pay attention to our peripheral nerve damage induces pro-inflammatory reactions in the spinal cord of rodents and humans, and can cause chronic neuropathic pain.
The microglia of the spinal cord are involved in this pro-inflammatory response.
However, the treatment of microglia is not effective for patients with neuropathic pain.
This indicates that there may be other types of cells that affect neuroimmune responses and pain hypersensitivity.
In addition, while powerful analgesics play an analgesic effect, they also bring some side effects.
This is related to a basic biological fact: the pathogenesis of pain involves many types of cells, and current treatments lack cell type specificity.
Therefore, these analgesics are solving the unfavorable changes of certain cells to relieve pain, but this may change the specific functions of other cells and cause undesirable side effects.
On March 4, 2021, the MarkJ.
Zylka research team of the University of North Carolina published an article in Neuron and found that there is a class of macrophages expressing Mrc1 in animal models of neuropathic pain.
The anti-inflammatory function of macrophages is weakened, which can promote the expression of CD163.
Re-enhance its anti-inflammatory function.
The researchers used single-cell sequencing technology to analyze the lumbar spinal cords of nerve-injured mice and sham-operated mice, and found 7 major types of cells and 66 cell subtypes.
Furthermore, the number of macrophages expressing Macro1 and Macro2 in the spinal cord of mice with nerve injury was significantly reduced.
These two types of macrophages express mannose receptor (Mrc1, also known as CD206), but do not express specific microglia.
Sex receptor Tmem119.The number of Mrc1+ macrophages in the nerve injury model decreases.
According to their spatial expression, Mrc1 positive macrophages are further subdivided into Mrc1+ meningeal macrophages (MMs) distributed in the subdural surrounding the spinal cord, and those in the perivascular space of the spinal cord.
Mrc1+ perivascular macrophages (PVMs) and Mrc1+ macrophages in the dorsal root.
They found that the number of meningeal macrophages in the neuropathic pain model was significantly reduced, while the perivascular macrophages and macrophages in the dorsal root remained unchanged.
CD163 is a type I membrane protein, a member of the scavenger receptor superfamily, marking anti-inflammatory macrophages.
In the sham operation group, the expression of CD163 on Mrc1+meningeal macrophages and Mrc1+perivascular macrophages increased with the passage of injury time, but the co-expression of Mrc1+meningeal macrophages and CD163 in the neural pain model appeared obstacles.
This indicates that the number of anti-inflammatory Mrc1+ meningeal macrophages is reduced in the neuropathic pain model.
After the researchers specifically cleared Mrc1+ macrophages, the mice in the sham-operated group were significantly similar to the pain abnormalities of the neural pain model mice.
In addition, microglia were activated in large numbers.
Previous studies have shown that the typical feature of peripheral nerve injury is the activation of microglia.
This indicates that the balance between anti-inflammatory (Mrc1+ macrophages) and pro-inflammatory (microglia) is destroyed after nerve injury.
Since the above studies found that the expression of CD163 in Mrc1+ meningeal macrophages in the neural pain model is reduced, what will happen to promote the expression of CD163? Therefore, the research team loaded the expression of CD163 on mannosylated polyethyleneimine nanoparticles (mPEIs) to specifically promote the expression of CD163 (mpCD163) in Mrc1+ meningeal macrophages.
Promoting the expression of CD163 to alleviate the inflammatory response of nerve injury.
They found that the injection of mpCD163 after nerve injury can significantly reduce mechanical pain sensitivity, and this pain relief effect can last for about a month.
In addition, the injection of mpCD163 can also reduce the number of microglia and astrocytes after nerve injury.
In general, this article found that the balance of anti-inflammatory cells and pro-inflammatory cells in the spinal cord after nerve injury was broken: Mrc1+ macrophages decreased, and microglia increased.
After promoting the expression of CD163 by Mrc1+ macrophages, it can effectively restore this balance and relieve pain.
This answers why some painkillers that specifically target microglia do not work.
[References] 1.
https://doi.
org/10.
1016/j.
neuron.
2021.
02.
018 The pictures in the article are all from the references
The microglia of the spinal cord are involved in this pro-inflammatory response.
However, the treatment of microglia is not effective for patients with neuropathic pain.
This indicates that there may be other types of cells that affect neuroimmune responses and pain hypersensitivity.
In addition, while powerful analgesics play an analgesic effect, they also bring some side effects.
This is related to a basic biological fact: the pathogenesis of pain involves many types of cells, and current treatments lack cell type specificity.
Therefore, these analgesics are solving the unfavorable changes of certain cells to relieve pain, but this may change the specific functions of other cells and cause undesirable side effects.
On March 4, 2021, the MarkJ.
Zylka research team of the University of North Carolina published an article in Neuron and found that there is a class of macrophages expressing Mrc1 in animal models of neuropathic pain.
The anti-inflammatory function of macrophages is weakened, which can promote the expression of CD163.
Re-enhance its anti-inflammatory function.
The researchers used single-cell sequencing technology to analyze the lumbar spinal cords of nerve-injured mice and sham-operated mice, and found 7 major types of cells and 66 cell subtypes.
Furthermore, the number of macrophages expressing Macro1 and Macro2 in the spinal cord of mice with nerve injury was significantly reduced.
These two types of macrophages express mannose receptor (Mrc1, also known as CD206), but do not express specific microglia.
Sex receptor Tmem119.The number of Mrc1+ macrophages in the nerve injury model decreases.
According to their spatial expression, Mrc1 positive macrophages are further subdivided into Mrc1+ meningeal macrophages (MMs) distributed in the subdural surrounding the spinal cord, and those in the perivascular space of the spinal cord.
Mrc1+ perivascular macrophages (PVMs) and Mrc1+ macrophages in the dorsal root.
They found that the number of meningeal macrophages in the neuropathic pain model was significantly reduced, while the perivascular macrophages and macrophages in the dorsal root remained unchanged.
CD163 is a type I membrane protein, a member of the scavenger receptor superfamily, marking anti-inflammatory macrophages.
In the sham operation group, the expression of CD163 on Mrc1+meningeal macrophages and Mrc1+perivascular macrophages increased with the passage of injury time, but the co-expression of Mrc1+meningeal macrophages and CD163 in the neural pain model appeared obstacles.
This indicates that the number of anti-inflammatory Mrc1+ meningeal macrophages is reduced in the neuropathic pain model.
After the researchers specifically cleared Mrc1+ macrophages, the mice in the sham-operated group were significantly similar to the pain abnormalities of the neural pain model mice.
In addition, microglia were activated in large numbers.
Previous studies have shown that the typical feature of peripheral nerve injury is the activation of microglia.
This indicates that the balance between anti-inflammatory (Mrc1+ macrophages) and pro-inflammatory (microglia) is destroyed after nerve injury.
Since the above studies found that the expression of CD163 in Mrc1+ meningeal macrophages in the neural pain model is reduced, what will happen to promote the expression of CD163? Therefore, the research team loaded the expression of CD163 on mannosylated polyethyleneimine nanoparticles (mPEIs) to specifically promote the expression of CD163 (mpCD163) in Mrc1+ meningeal macrophages.
Promoting the expression of CD163 to alleviate the inflammatory response of nerve injury.
They found that the injection of mpCD163 after nerve injury can significantly reduce mechanical pain sensitivity, and this pain relief effect can last for about a month.
In addition, the injection of mpCD163 can also reduce the number of microglia and astrocytes after nerve injury.
In general, this article found that the balance of anti-inflammatory cells and pro-inflammatory cells in the spinal cord after nerve injury was broken: Mrc1+ macrophages decreased, and microglia increased.
After promoting the expression of CD163 by Mrc1+ macrophages, it can effectively restore this balance and relieve pain.
This answers why some painkillers that specifically target microglia do not work.
[References] 1.
https://doi.
org/10.
1016/j.
neuron.
2021.
02.
018 The pictures in the article are all from the references