A breakthrough test developed researchers to measure pain in patients could help stem the tide of the opioid crisis.

A study published in the journal Molecular Psychiatry tracked hundreds of participants 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 the senior author of 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, the author said never has there been a more important time to administer drugs to patients responsibly.

The authors 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 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.

In addition to providing an objective measure of pain, the 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 the author, 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."

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. 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). 

"Through precision medicine you're giving the patient treatment that is tailored directly to them and their needs," the author 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."

Moving forward, the 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.

https://medicine.iu.edu/news/2019/02/iu-school-of-medicine-makes-breakthrough-towards-developing-blood-test-for-pain/

https://www.nature.com/articles/s41380-018-0345-5

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Ftowards-precision&filter=22