By Ashley Brenton, PhD
Have you ever noticed that people feel pain differently? One person stubs a toe and has to stay
home from work for a week, whereas another person gets kicked by a horse, stands up and
walks off. It turns out one reason for this is individual differences in our genes. Additionally,
how people respond to pain medications is also affected by differences in our genes. This
makes pain an obvious focus for precision medicine.
There are over 100 million Americans suffering from chronic pain, according to National
Academy of Medicine (formerly the Institute of Medicine). Chronic pain is a major burden on
the healthcare system, patients, and caretakers. Costs associated with chronic pain exceed
$635 billion annually.
One gene that has been implicated in individual pain perception is the Catechol-O-
methyltransferase (COMT) gene. COMT degrades neurotransmitters, like epinephrine,
dopamine and norepinephrine. Mutations in the COMT gene can result in less enzyme activity,
which results in higher levels of neurotransmitters. There are a number of well-replicated
studies that have implicated COMT activity with pain perception. Those with high levels of
COMT activity have lower levels of catecholamines and experience lower pain sensitivity. On
the other hand, those with the lowest COMT activity have the highest levels of catecholamine
neurotransmitters and thus, the highest pain sensitivity.
In addition to influencing how an individual feels pain, our genes also affect how we respond to
pain medications. There are well known genetic variants, such as those in the cytochrome P450
gene family, that determine how a person metabolizes medications. Mutations in these genes
determine how quickly a drug is broken down, what the therapeutic dose should be and the
risk of side effects. Beyond how we metabolize medications, our genes also determine how we
respond to the medication. In fact, these genetic mutations are so well established, that the
FDA has a number of pharmacogenomics biomarkers listed on their website. These biomarkers
are drug-specific and may affect the dosing information, indications for use and warnings. In
some cases, the FDA recommends pharmacogenetic testing of specific mutations before a
medication is prescribed. One example of this is the black box warning for HLA-B*1502 testing
prior to carbamazepine use. A patient carrying the HLA-B*1502 allele is susceptible to serious
and sometimes fatal dermatological side effects if exposed to carbamazepine.
SOTERIA is available to help our clients understand their individual pain perception, how this
affects expectations following surgery or recovery, and managing chronic or oncological pain
conditions. SOTERIA provides expertise in interpreting genomic sequence data to identify the
best medications for each patient.
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Dr. Ashley Brenton is a precision medicine veteran. A classically trained molecular biologist, Dr.
Brenton’s career has focused on applying genomics to public health issues and she has a proven
track record in building scientific evidence for precision medicine, as well as bringing successful
precision medicine tests to commercialization. Dr. Brenton began her career at Johns Hopkins
and her background in public health and genomics led her to Soteria, where she strives to help
patients and their families navigate the often-complicated world of medicine through clear
communication and an expert understanding of cutting-edge medical testing.