In Laboratory, SLU Scientist Turns Off Chemo Pain
In a recent paper published in the journal Pain, Saint Louis University researchers describe their success in an animal model in
turning off the excruciating pain that often accompanies a colorectal cancer drug.
Daniela Salvemini, Ph.D., professor of pharmacology and physiology at SLU, studies
pain pathways, the series of interactions between molecular-level components that
lead to pain in the body.
One type of pain she examines is chemotherapy induced neuropathic pain (CINP), a debilitating side effect of chemotherapy that can appear as tingling or
numbness in the hands and feet, shooting or burning pain in the limbs, or can feel
like hot or cold temperature extremes. In addition to causing patients suffering,
CINP is often a limiting factor when it comes to treatment.
“Thanks to the increased efficacy of cancer treatment, there are nearly 14 million
cancer survivors in the United States,” Salvemini said. “Many of these survivors suffer
from long-term side effects of CINP, for which there are no proven strategies for
prevention or treatment.
“This is a huge unmet medical need.”
In her current paper, Salvemini studied the platinum-based chemotherapy drug oxaliplatin
which is widely used to treat colorectal cancer. Over 60 percent of patients who received
oxaliplatin develop CINP, and it can last for years after treatment.
The research team found that the pain pathway associated with this drug was driven
by increased expression of an enzyme, adenosine kinase, in astrocytes (a type of central
nervous system cell) and decreased adenosine signaling at a key receptor, A3AR. By
supplementing this signaling with A3AR agonists, the researchers were able to block
the development of CINP without interfering with the anticancer properties of platinum
These findings advance researchers’ understanding of pain pathways and provide new
information about how drugs may be able to treat chemotherapy pain. Perhaps most encouraging,
existing A3AR agonists currently are being studied in advanced clinical trials as
novel anticancer agents. This paper makes a strong case for evaluating those drugs
for use together with oxaliplatin to limit CINP while treating cancer.
The research was funded by the National Institutes of Health’s National Cancer Institute
(NIH RO1 CA169519) and National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Research Program (Z01 DK031117-26).
Other researchers on the study include Carrie Wahlman, Timothy M. Doyle, Joshua W.
Little, Livio Luongo, Kali Janes, Zhoumou Chen, Emanuela Esposito, Dilip K. Tosh,
Salvatore Cuzzocrea and Kenneth A. Jacobson.
Daniela Salvemini, Ph.D.
Salvemini’s notable career includes studying with a Nobel Laureate, discovering peroxynitrite,
a key molecule in the development of pain and inflammation, and uncovering some of
the reasons why certain chemotherapy drugs can cause patients extreme and lasting
pain. Salvemini was honored in 2014 by the Academy of Science of St. Louis for her
contribution to our understanding of pain with the Fellows Award, which recognizes
a distinguished individual for outstanding achievement in science.
“Dr. Salvemini has contributed more to the eventual control of pain and opioid-induced
tolerance than anyone else currently working in the field,” the Academy noted.
Saint Louis University School of Medicine
Established in 1836, Saint Louis University School of Medicine has the distinction
of awarding the first medical degree west of the Mississippi River. The school educates
physicians and biomedical scientists, conducts medical research, and provides health
care on a local, national and international level. Research at the school seeks new
cures and treatments in five key areas: cancer, liver disease, heart/lung disease,
aging and brain disease, and infectious diseases.