Summary: Researchers have identified biomarkers in the blood which can help determine the severity of a person’s pain level. The findings could help doctors to accurately measure pain and stem the opioid crisis.
Source: Indiana University.
A breakthrough test developed by Indiana University School of Medicine researchers to measure pain in patients could help stem the tide of the opioid crisis in Indiana, and throughout the rest of the nation..
A study led by psychiatry professor Alexander Niculescu, MD, PhD and published this week in the high impact Nature journal Molecular Psychiatry tracked hundreds of participants at the Richard L. Roudebush VA Medical Center in Indianapolis to identify biomarkers in the blood that can help objectively determine how severe a patient’s pain is. The blood test, the first of its kind, would allow physicians far more accuracy in treating pain–as well as a better long-term look at the patient’s medical future.
“We have developed a prototype for a blood test that can objectively tell doctors if the patient is in pain, and how severe that pain is. It’s very important to have an objective measure of pain, as pain is a subjective sensation. Until now we have had to rely on patients self-reporting or the clinical impression the doctor has,” said Niculescu, who worked with other Department of Psychiatry researchers on the study. “When we started this work it was a farfetched idea. But the idea was to find a way to treat and prescribe things more appropriately to people who are in pain.”
During the study, researchers looked at biomarkers found in the blood–in this case molecules that reflect disease severity. Much like as glucose serves as a biomarker to diabetes, these biomarkers allow doctors to assess the severity of the pain the patient is experiencing, and provide treatment in an objective, quantifiable manner. With an opioid epidemic raging throughout the state and beyond, Niculescu said never has there been a more important time to administer drugs to patients responsibly.
“The opioid epidemic occurred because addictive medications were overprescribed due to the fact that there was no objective measure whether someone was in pain, or how severe their pain was,” Niculescu said. “Before, doctors weren’t being taught good alternatives. The thought was that this person says they are in pain, let’s prescribe it. Now people are seeing that this created a huge problem. We need alternatives to opioids, and we need to treat people in a precise fashion. This test we’ve developed allows for that.”
In addition to providing an objective measure of pain, Niculescu’s blood test helps physicians match the biomarkers in the patient’s blood with potential treatment options. Like a scene out of CSI, researchers utilize a prescription database–similar to fingerprint databases employed by the FBI–to match the pain biomarkers with profiles of drugs and natural compounds cataloged in the database.
“The biomarker is like a fingerprint, and we match it against this database and see which compound would normalize the signature,” said Niculescu, adding that often the best treatment identified is a non-opioid drug or compound. “We found some compounds that have been used for decades to treat other things pair the best with the biomarkers. We have been able to match biomarkers with existing medications, or natural compounds, which would reduce or eliminate the need to use the opioids.”
In keeping with the IU Grand Challenge Precision Health Initiative launched in June 2016, this study opens the door to precision medicine for pain. By treating and prescribing medicine more appropriately to the individual person, this prototype may help alleviate the dilemmas that have contributed to the current opioid epidemic.
“In any field, the goal is to match the patient to the right drug, which hopefully does a lot of good and very little harm,” Niculescu said. “But through precision health, by having lots of options geared toward the needs of specific patients, you prevent larger problems, like the opioid epidemic, from occurring.”
Additionally, study experts discovered biomarkers that not only match with non-addictive drugs that can treat pain, but can also help predict when someone might experience pain in the future–helping to determine if a patient is exhibiting chronic, long-term pain which might result in future emergency room visits.
“Through precision medicine you’re giving the patient treatment that is tailored directly to them and their needs,” Niculescu said. “We wanted first to find some markers for pain that are universal, and we were able to. We know, however, based on our data that there are some markers that work better for men, some that work better for women. It could be that there are some markers that work better for headaches, some markers that work better for fibromyalgia and so on. That is where we hope to go with future larger studies.”
The study was supported by an NIH Director’s New Innovator Award and a VA Merit Award. Moving forward, Niculescu’s group looks to secure more funding through grants or outside philanthropy to continue and accelerate these studies–with the hopes of personalizing the approach even more and moving toward a clinical application. A self-described longshot at the start, Niculescu said that the work his group has done could have a major impact on how doctors around the world treat pain in the future.
“It’s been a goal of many researchers and a dream to find biomarkers for pain,” Niculescu said. “We have come out of left field with an approach that had worked well in psychiatry for suicide and depression in previous studies. We applied it to pain, and we were successful. I give a lot of credit for that to my team at IU School of Medicine and the Indianapolis VA, as well as the excellent environment and support we have.”
Other investigators involved in the study were Helen Le-Niculescu, PhD, Daniel Levey, Kyle Roseberry, Katherine Soe, MD, Jordan Rogers, Faisal Khan, MD, Tammy Jones, Seth Judd, Morgan McCormick, MD, Ann Wessel, Andrea Williams, Sunil Kurian and Fletcher White, MS, PhD.
The study supports an initiative established in 2017 by Indiana University. To build on IU’s existing expertise and research regarding addictions, IU President Michael McRobbie, along with Indiana Gov. Eric Holcomb and IU Health President and CEO Dennis Murphy, announced the Responding to the Addictions Crisis Grand Challenge initiative. This Grand Challenge initiative engages a broad array of IU’s world-class faculty, as well as IU’s business, nonprofit and government partners. The initiative aims to implement a collaborative, applied and comprehensive plan to reduce deaths from addiction, ease the burden of drug addiction on Hoosier communities, and improve health and economic outcomes. This statewide initiative is one of the nation’s largest and most comprehensive state-based responses to the opioid addiction crisis–and the largest led by a university.
Funding: The research was supported by the National Institutes of Health under Award Number IDP20D007363 and VA Merit Award 2I01CX000139. The content is solely the responsibility of Indiana University School of Medicine and does not necessarily represent the official views of the National Institutes of Health or the VA.
Source: Katie Duffey – Indiana University
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Open access research for “Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs” by A. B. Niculescu, H. Le-Niculescu, D. F. Levey, K. Roseberry, K. C. Soe, J. Rogers, F. Khan, T. Jones, S. Judd, M. A. McCormick, A. R. Wessel, A. Williams, S. M. Kurian & F. A. White in Molecular Psychiatry. Published February 12 2019.
Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs
We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.