Why your DNA matters in using the right pain medication

Managing pain is not just about picking the right drug, but matching the right medication to your DNA. A simple genetic test, done before prescribing, could help doctors predict which pain medicine will work best for you and which might cause dangerous side effects.

Pain treatment has always been a trial-and-error process, but a new study shows it does not have to be.

“Despite advances in pharmacologic options, interindividual variability in response and susceptibility to adverse effects continues to challenge clinicians,” wrote the researchers, including first author Ivan Martin da Silva.

The role of pharmacogenetics

Even with progress in medications and medical technology, many patients continue to experience severe pain, particularly following surgery. Persistent pain affects not only the body but also emotional well-being.

It can affect other systems, leading to complications. How one person reacts to analgesics differs from another, not only in effects, but also in side effects.

However, for better pain relief, doctors often combine multiple drugs. Certain combinations can cause further adverse reactions in the body.

Pharmacogenetics paves the way for better pain management by predicting a patient’s response to specific drugs. This approach analyzes genes responsible for the secretion of enzymes that metabolize medications.

Matching pain medication and DNA

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for acute and chronic pain, including musculoskeletal, cancer-related, and post-surgical pain. They are also effective at reducing swelling and fever.

Pain, inflammation, and fever are caused by compounds called prostaglandins. NSAIDs block or lower the levels of prostaglandins to reduce these effects. 

Since they are highly effective, doctors widely prescribe NSAIDs. But their pharmacokinetics, that is, how the drug works in the body, and potential side effects vary among individuals.

This variation results from genetic differences in the enzymes that break down these drugs. For example, if the enzyme acts slowly, the drug can build up in the body, causing severe side effects. The faster the enzyme works, the quicker the drug is cleared.

Genetic differences in drug metabolism

Researchers have studied the CYP2C9 gene to better understand why NSAID metabolism varies among individuals. This gene provides instructions for making the enzyme CYP2C9, which metabolizes NSAIDs. 

Variations in the gene can increase or decrease enzyme production. In individuals with reduced CYP2C9 function, NSAID metabolism is slower.

Doctors must then prescribe a lower dose or choose a different medication, which can benefit patients on long-term NSAID treatment, especially older adults or those with kidney or heart issues.

Personalized opioid therapy

While NSAIDs are often the first step in managing pain, some patients need stronger medications. In those cases, opioids may be prescribed, often to treat nerve pain, post-surgical pain, or cancer-related pain. 

The CYP2D6 enzyme in the liver metabolizes most opioids. Studies support genotyping CYP2D6 for opioids such as codeine and tramadol.

According to researchers, more gene-drug associations with opioid drugs may exist, but are not yet confirmed. Testing the CYP2D6 genotype before prescribing opioids can help avoid treatment failure or adverse drug reactions.

In the future, testing broader genes like CYP3A4, OPRM1, or COMT could be beneficial for treatments with opioids, but further validation is needed. 

Genetic testing for nerve pain medicine

Genetics also influence how people respond to nerve pain drugs such as antidepressants, anticonvulsants, and gabapentinoids.

These medications are prescribed for first- or second-line treatment for nerve pain. Most of the drugs have a narrow therapeutic index (NTI), meaning the safe dose is very close to the toxic dose.

Nerve pain drugs can cause adverse side effects. ​​CYP2D6 and CYP2C19 are the main enzymes that metabolize various opioids. Genotyping the enzymes helps doctors adjust dosages for effectiveness and reduce adverse drug reactions (ADRs).

Human Leukocyte Antigen (HLA) is a set of genes that play a critical role in the immune system. In some individuals, certain HLA variants recognize opioid drugs as threats, causing life-threatening hypersensitivity reactions.

Genotyping HLA before prescribing these drugs can prevent such reactions. Using genetics to guide drug choice can make nerve pain treatment more precise and safer.

Challenges of pharmacogenetics

The cost of pharmacogenetic tests has decreased recently. However, healthcare reimbursement and accessibility factors remain challenging. 

Interpreting the test results requires expert knowledge, which means additional training for healthcare professionals is necessary. Effective collaboration among specialists from relevant fields is also essential to implement this extra step in clinical practice. 

Engaging all stakeholders is necessary to integrate the new genetic testing process into existing healthcare routines. Additionally, healthcare professionals need to monitor the outcomes to track the effectiveness of the new approach. 

The future of pain management

In the future, pharmacogenetics in pain management may move beyond single-gene tests to multigene panels analyzing multiple genes affecting drug metabolism. 

It may also enable assessment of polygenic risk scores, which are numerical values indicating an individual’s susceptibility to diseases and ADRs. 

Advanced technologies for gene sequencing, machine learning, and data analysis could help predict the mechanism of action of the drug. 

Pharmacogenetics can also be combined with proteomics, metabolomics, and epigenomics to understand the variations in responses to pain medicines. Overall, it can make pain management treatments safer and more effective, reducing side effects and minimizing opioid use. 

With pharmacogenetics, your next pain prescription could be tailored to your DNA.

The research is published in the journal Biomedicines.

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