Format

Send to

Choose Destination
Mol Psychiatry. 2019 Feb 12. doi: 10.1038/s41380-018-0345-5. [Epub ahead of print]

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs.

Author information

1
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. anicules@iupui.edu.
2
Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. anicules@iupui.edu.
3
Indianapolis VA Medical Center, Indianapolis, IN, USA. anicules@iupui.edu.
4
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
5
Indianapolis VA Medical Center, Indianapolis, IN, USA.
6
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
7
Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
8
Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN, USA.

Abstract

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.

PMID:
30755720
DOI:
10.1038/s41380-018-0345-5

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center