Our vision is that we need a test that will quantify pain—at point of care and at home. While many factors contribute to this complex phenomenon, many of the fundamental mechanisms of the sensation of pain converge on specific metabolites—chemicals made in our bodies. Many human sensations are mediated by molecules (happy: serotonin; hungry: ghrelin; sleepy: melatonin). Pain may have specific molecular signatures as well. A test that measures the levels of these key molecules may guide a number of crucial decisions:
- a medical provider will be able to determine whether to send a post-op patient home with 30 or 3 oxycontin pills, or none at all;
- a clinical researcher will be better equipped to find the difference between a new drug and a placebo;
- a migraneur will get an objective evidence of whether or not a new treatment regimen is working.
One of the major success stories in metabolite-focused pain management is calcitonin gene-related peptide (CGRP), a neurotransmitter involved in the transmission of pain. Blocking this molecule with monoclonal antibodies was hypothesized to relieve pain. Three independent products (Aimovig, Amgen/Novartis; Ajovy, Teva; Emgality, Eli Lilly) reached FDA approval in 2018.
The comprehensive measurement of multiple metabolites in body fluids is called metabolomics. Two key technologies that make it possible are nuclear magnetic resonance (NMR) and mass-spectrometry (MS). NMR relies on the same physical effect as MRI, but instead of placing the whole body in a big magnet, a sample of a biofluid (urine or blood) is used. NMR measures the metabolite levels with great precision, but is not very sensitive, limiting the number of molecules that can be measured to less than 100. In MS, molecules in a sample are weighed and counted. MS is sensitive down to parts-per-billion levels, and thousands of molecules can be measured from a small drop of biofluid. Tremendous progress over the last 20 years has been made with NMR and MS instrumentation, and both methods find increasing use both in research and clinical labs. Metabolomics has been used previously to find biomarkers associated with cancer pain, rheumatoid arthritis, chronic fatigue syndrome, fibromyalgia, complex regional pain syndrome, interstitial cystitis/bladder pain syndrome, and migraines.
In order for these exciting findings to become a widely used clinical test, a number of hurdles must be overcome.
- biological variability: the chemical composition of human body changes when we eat and throughout the day. Even though samples are commonly collected first thing in the morning, after fasting or a standardized meal, the differences between people are so great that statistically sound interpretation can be difficult to make.
- sample acquisition: it is difficult and expensive to collect a large number of samples. A general-purpose test that will need to be validated on thousands or even tens of thousands of samples;
- data sharing and processing: modern mass-spectrometry generates an enormous of data that to date remains difficult to share and analyze independently. The sample processing and data processing methods vary from lab to lab, and two different studies cannot be compared to each other;
The goal of Aumics is to overcome these challenges and create an affordable, robust, and objective body chemistry test that guides the personalized management of pain.
Coming soon
Tatiana Award: a prize for researchers who work on genomic, proteomic, metabolomic, or other quantitative studies of pain. Call for nominations: June 15, 2019
Omics of Pain Conference
The Aumics Test
Pain is not your destiny 