A researcher from Saint Louis University has discovered a pain pathway, and is now determining if either of two key molecules can be used as biomarkers for pain associated with chemotherapy-induced peripheral neuropathy (CIPN), endometriosis, interstitial cystitis and vulvodynia.
SLU scientist and principal investigator Daniela Salvemini, Ph.D., received a $363,000 grant from The Mayday Fund to advance her work to understand pain in order to develop new painkillers.
“It is exciting to reach the moment when you can take your research from the laboratory to the clinic,” said Salvemini, who is professor of pharmacology and physiology at SLU.
In previous work, Salvemini discovered pain pathways – the molecular series of events that lead to pain – that helped researchers understand how pain occurs. The pain pathways are dependent on two molecules: S1PR1 and A3AR (sphingosine 1-phosphate receptor subtype 1 and A3 adenosine receptor subtype). By modulating these molecules, scientists were able to block and reverse pain. This finding is particularly encouraging because a drug that modulates S1PR1 is already on the market and one that modulates A3AR is in advanced clinical trials.
Salvemini’s next goal is to see if S1PR1 and A3AR can serve as biomarkers in the clinic.
Based on her previous work, Salvemini believes that higher levels of S1PR1 and/or A3AR correlate with chronic pain incidence and intensity and predict the development of chronic pain syndromes, suggesting these receptors may be good targets for new drugs that target these pathways to treat or prevent chronic pain syndromes.
“Our goal is to take this exciting basic science work a step further and study to see if these molecules can serve as biomarkers in people, helping us to identify patients who would and who would not benefit from drugs that target this pathway and providing a more personalized approach to pain treatment,” Salvemini said. “This study focuses on high impact, high potential chronic pain-associated conditions.”
In the newly funded study, Salvemini and her team will partner with Saint Louis University clinicians in the SLUCare practice to study patients with four different conditions that cause pain: chemotherapy-induced neuropathic pain (CIPN), with Jack Lionberger, M.D., Ph.D., assistant professor of hematology and medical oncology; endometriosis with Patrick Yeung Jr., M.D., associate professor of obstetrics, gynecology and women’s health; interstitial cystitis with E. Cristian Campian, M.D., Ph.D., assistant professor of obstetrics, gynecology and women’s health; and vulvodynia with Cherie LeFevre, M.D., associate professor of obstetrics, gynecology and women’s health.
“The direct and indirect economic costs of endometriosis, which is mostly from pain and lost productivity, is estimated to be upwards of $20 billion annually in the US alone. Having a better way to treat endometriosis-related pain that does not just treat symptoms and without the negative side effects of high-dose anti-inflammatories or narcotics, is long overdue. We must do better do better for women, and this research collaboration has great potential,” said Patrick Yeung Jr., M.D., associate professor of obstetrics, gynecology and women’s health, who is partnering with Salvemini on the endometriosis study.
“The problem of chemotherapy-induced pain is a critical unmet need that severely impacts our patients struggling with cancer and their ability to receive potentially lifesaving treatment. While SLU has had an enduring commitment to managing chronic pain, Dr. Salvemini’s work represents an important, innovative approach that will directly benefit the population that our Cancer Center serves. This ‘bench to bedside’ project is central to the clinical research mission of our hematology and oncology division, and I am excited to be a part of this work,” said Jack Lionberger, M.D., Ph.D., assistant professor of hematology and medical oncology, who is working on the chemotherapy-induced pain study.
If one or both of these two molecules does prove to be a useful biomarker, researchers will have laid the groundwork for a proof-of-concept trial to test a drug that interferes with the molecular pathways engaged by these molecules and could serve as a new non-narcotic painkiller.