It's not just neurons that cause pain, there are another type of cell!

Pain is an ongoing symptom of cancer that can turn a patient's life
upside down.
Researchers have relied on opioids for decades to provide relief, while trying to find alternative solutions due to the side effects of the drugs, with little
success.

Now, researchers at Chinese University in Hong Kong have discovered a new mechanism that they say could be the center of
cancer pain.
They found that macrophages (white blood cells that are part of the body's immune system) have penetrated into lung tumors and can begin to mimic neurons and really sense pain
.
In a study published Oct.
7 in Science Advances, the team dubbed the phenomenon a "macrophage-to-neuron-like transition," or MNT, which may explain why some cancer patients are unable to relieve pain by using traditional painkillers, said
co-author Patrick Tang, a biochemist at Chinese University in Hong Kong.

Tracey Ignatowski, a pathologist at the University of Buffalo, said: "A lot of neuropathic pain is difficult to treat
.
" She was not involved in the current study
.
"We are looking for new ways to manage or reduce pain more effectively, and [MNT] offers a potentially unique target
for therapeutic potential.
"

Previous research in the field has found that innervation, the site where the nervous system begins to communicate with tumor cells, plays an important role
in tumor growth and cancer progression.
To understand the origin of pain-sensing neurons in lung cancer, Tang and his colleagues began their study, using RNA sequencing technology to study
tumor cells obtained from mice with lung cancer.
That's when they realized that these supposed neurons were actually neuron-like cells
that resembled macrophages.
Other studies have shown that macrophages can mimic many other types of cells, adding credibility to the new findings, but how these cells accomplish this transition remains a mystery
.

Therefore, the team used chromatin immunoprecipitation to analyze genomic changes occurring in macrophages to obtain neurophenotypes
.
Based on the alterations in gene expression revealed by this technique, they speculated that a transcription factor called SMAD3 might have initiated the transition
.
When the researchers used gene deletions and drugs to suppress SMAD3 activity, immunodeficient mice had fewer neuron-like cells than control mice, and the animals also showed fewer pain-driven behaviors such as licking and withdrawing
.

As a researcher who has studied neuron-macrophage interactions for more than 20 years, Ignatowski says she's excited
about the potential to use the findings to further work in the field.
However, she said she also doubts whether the results apply to humans and whether the same mechanism occurs in other types of
cancer.
"Eventually, they may find that, under the right conditions, macrophages can actually undergo this transition
to neuron-like phenotypes in every disease," she said.
So this is something
that needs to be investigated.
”

Daniel Adams, a molecular biologist at Maryland-based biotech company Creatv MicroTech, who was not involved in the study, has reservations
.
He told The Scientist: "I'm always a little hesitant to jump to conclusions
about mouse models.
" Studying the immune system in immunodeficient animals is counterintuitive
.
"But you have to start somewhere," he acknowledged, adding that the work is interesting and involves the use of many cutting-edge technologies, but how that translates to humans remains to be seen
.

Tang and his colleagues agree that these are the limitations of
their work.
But for them, there's a bigger limitation is their focus: "When we detect pain, we're trying to demonstrate how to demonstrate that association in rodents," Tang said
.
For this reason, the team now plans to conduct a study in cancer patients to better understand how their new mechanism is associated with cancer pain and whether there are ways to manage or reduce it
.

"I want cancer patients to feel hopeful," Tang said
.
"Some of them are really frustrated
with the pain and the quality of life.
I just want them to know that someone is doing this
.
”