A new study has found that chemotherapy might cause pain by triggering stress and inflammation in immune cells—not just by damaging nerves.
This discovery helps explain why many cancer patients experience serious and long-lasting pain after chemotherapy and points to possible new ways to prevent it.
The study was led by scientists at Weill Cornell Medicine and Wake Forest University School of Medicine. It was published in the journal Science Translational Medicine. The researchers focused on a condition called chemotherapy-induced peripheral neuropathy (CIPN).
This condition affects about half of all people who receive chemotherapy. It causes tingling, numbness, and pain in the hands and feet. For many patients, the discomfort is so bad that they have to stop their cancer treatment early.
The researchers found that the pain is linked to an immune system pathway called IRE1α-XBP1. This pathway works like a stress alarm inside immune cells.
When immune cells become stressed, this alarm goes off, leading to inflammation. Earlier research from the same team showed that this pathway can cause pain after surgery. Now, they’ve shown it also plays a big role in pain caused by chemotherapy.
To study this, scientists used mice to model what happens to nerves during chemotherapy. They gave the mice a common cancer drug called paclitaxel. This drug caused the immune cells to produce harmful molecules called reactive oxygen species.
These molecules created stress inside the cells and triggered the IRE1α pathway. Once activated, the immune cells became inflamed and moved toward an area in the nervous system called the dorsal root ganglia—where sensory nerves connect the limbs to the spine.
Once there, the inflamed immune cells released chemicals that irritated and damaged the nerves. This caused the mice to show signs of pain that are similar to what cancer patients feel: nerve damage, sensitivity to cold, and pain.
But the scientists didn’t stop there. They tried blocking the IRE1α pathway in immune cells using genetic tools, and the mice had much less pain and less nerve damage. Then they tested a drug that also blocks IRE1α.
This drug is already in early clinical trials for treating cancer. When mice were given both paclitaxel and the IRE1α-blocking drug, they showed fewer pain symptoms and healthier nerves.
Dr. Juan Cubillos-Ruiz, one of the lead authors, said this shows chemotherapy pain is not just about nerve damage. It’s also about how the immune system reacts under stress. He added that blocking the IRE1α pathway might help patients stay on their chemotherapy without suffering from nerve pain.
This could be a big deal because it means one drug might both fight cancer and reduce one of the worst side effects of treatment. It could help patients feel better and stick to their treatment plan.
The researchers also ran a small test with women being treated for gynecologic cancers. Blood samples taken during their treatment showed that those who developed severe nerve pain had higher levels of IRE1α activity—even before they felt symptoms.
This means a simple blood test in the future could help doctors know who is more likely to get nerve pain from chemotherapy. Doctors could then take action early to prevent the problem, possibly using IRE1α-blocking drugs.
In summary, this study changes how we think about pain caused by chemotherapy. It’s not just about damaged nerves—it also involves the immune system. The discovery opens the door to new treatments that might reduce pain and improve the lives of cancer patients.
If you care about cancer, please read studies that artificial sweeteners are linked to higher cancer risk, and how drinking milk affects risks of heart disease and cancer.
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