SLU scientist examines potential biomarkers for pain linked to debilitating health conditions

With new funding from The Mayday Fund, a Saint Louis University researcher will leverage her discovery of a pain pathway to determine if either of two key molecules can be used as biomarkers for pain associated with four debilitating health conditions: chemotherapy-induced peripheral neuropathy (CIPN), endometriosis, interstitial cystitis and vulvodynia.

SLU scientist and principle investigator Daniela Salvemini, Ph.D., will use the $363,000 grant 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.

Approximately 100 million American adults suffer from chronic pain, costing society around $600 billion annually. This burden will grow with an aging population suffering from diabetes, stroke and cancer.

Further, chronic pain offers a difficult choice for many patients and their doctors: opt to take opioid pain medicines that carry a risk of addiction and severe side effects that can decrease quality of life, or suffer terribly.

The medical community recognizes an urgent need for safer, non-addictive pain medications.

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.

A biomarker is something that can be measured -- a scientific yardstick to see who is suffering from pain via this molecular pathway and, in the future, may be able to tell us if medicines can work to stop or limit this pain. Identifying biomarkers is an important step in the scientific process to find a new painkiller; without a biomarker, it would be difficult to know if a medication is easing pain or if pain is subsiding for another reason. This will also allow doctors to select those patients that will be more likely to respond to the medicine in a personalized approach.

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," Yeung said.

Similarly, chemotherapy-induced peripheral neuropathy is a debilitating burden for patients undergoing cancer treatment.

"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 life saving 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," Lionberger said.

If patients suffering pain have a correlating high level of these molecules in their blood or tissue, these markers may be able to serve as useful measurements to know that the pain pathway is activated and that patients might benefit from a drug that specifically targets these molecules.

In future research, Salvemini aims to expand this work to other study sites and to include patients with multiple sclerosis, traumatic brain and spinal cord injuries, fibromyalgia, diabetes and temporomandibular joint and muscle disorders (TMJ).

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.