Pain & Anesthesia and Your DNA — Why Pain Medications Work Differently for You

What Decode+ Shows You

Find out why codeine didn't work, why you needed more medication after surgery, or why pain hits harder for you. Decode+ analyzes five genes that shape how you experience pain and respond to pain medications — then translates that into plain-language findings you can share with your doctor or anesthesiologist.

Rather than starting with gene names, your results are organized around the experiences that bring people here: medications that didn't provide relief, post-surgical pain that was harder to manage than expected, or a sense that you feel pain more intensely than others.

What Decode+ Covers

Your results are framed around clinical scenarios, not gene names. They address:

• Whether certain pain medications may be ineffective for you — Some people cannot convert codeine or tramadol into their active forms. Your results identify whether your genetics affect this pathway.
• Whether standard opioid doses may provide less relief — Genetic variation in the mu-opioid receptor can mean you need higher morphine doses to achieve the same pain relief as others.
• Whether you may experience pain more intensely than average — Variants affecting catecholamine metabolism and central sensitization pathways can influence baseline pain perception.
• Which opioid medications may be affected — Codeine, tramadol, hydrocodone, and oxycodone are all metabolized through pathways covered in Decode+.

How It Works

1. Upload your DNA data from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA (or use data you've already uploaded).
2. Your raw data is analyzed to extract variants in CYP2D6, OPRM1, COMT, BDNF, and ANKK1 and assign genotypes, diplotypes, and phenotype classifications.
3. See your results in Decode+ with personalized findings organized by clinical scenario and published research citations.

Key Clinical Evidence

• OPRM1 and morphine dosing: The OPRM1 A118G variant (rs1799971) is associated with significantly higher morphine dose requirements for adequate post-operative pain control. Patients with the G allele may need 30-50% more morphine equivalents (Crist & Berrettini, 2014).
• CYP2D6 and codeine: CPIC guidelines recommend avoiding codeine in CYP2D6 poor metabolizers (no analgesic effect) and ultrarapid metabolizers (risk of toxicity). This is one of the most established drug-gene interactions in pharmacogenomics (Crews et al., 2021).
• COMT and pain sensitivity: The COMT Val158Met polymorphism (rs4680) affects catecholamine metabolism and has been consistently associated with differences in pain perception. Met/Met carriers show increased pain sensitivity in experimental and clinical settings (Zubieta et al., 2003).

Learn More

• See a sample — preview what your results look like before you start
• Why doesn't codeine work for me? — the CYP2D6 explanation for codeine non-response

Genes Analyzed

Decode+ focuses on five genes with clinical evidence for pain sensitivity and analgesic response:

• CYP2D6 — Metabolizes codeine, tramadol, hydrocodone, and oxycodone. Metabolizer status determines whether prodrug opioids are converted to their active forms.
• OPRM1 — Encodes the mu-opioid receptor, the primary target of morphine and most opioid analgesics. The A118G variant affects receptor binding and dose requirements.
• COMT — Catechol-O-methyltransferase regulates catecholamine levels in the brain. The Val158Met variant is associated with differences in baseline pain sensitivity.
• BDNF — Brain-derived neurotrophic factor modulates central sensitization and pain processing. The Val66Met variant has been linked to altered pain perception in clinical studies.
• ANKK1 — Located near the DRD2 dopamine receptor gene. The Taq1A variant affects dopamine receptor density and has been associated with differences in analgesic response and pain modulation.

Limitations

• Decode+ analyzes five genes for pain & anesthesia. Pain is complex and influenced by many additional genetic and non-genetic factors including inflammation, psychological state, and prior pain history.
• Consumer genotyping arrays cannot detect CYP2D6 gene deletions or duplications, which affect some metabolizer phenotype classifications.
• Pharmacogenomic results do not predict how much pain you will experience. They indicate how your genetics may affect pain sensitivity and opioid metabolism.
• This is not medical advice. All pain management and anesthesia decisions should be made with your healthcare provider. See the full limitations page.

Important Disclaimer

Decode+ is for educational and informational purposes only. It does not constitute medical advice, diagnosis, or treatment recommendations. Pharmacogenomic information is one factor among many that clinicians consider when making pain management and anesthesia decisions. Do not change, stop, or start any medication based on these results without consulting your healthcare provider. Decode+ does not address opioid addiction risk, which involves different genetic and environmental factors.

Related

• Psychiatric Medication — CYP2D6 also metabolizes antidepressants and ADHD medications. If you take psychiatric medications, your genetics affect those too.
• Cannabis & CBD — The same CYP enzymes that affect pain medication also determine how you process THC and CBD.
• Celiac & Gluten Screening — Rule out celiac disease from your existing DNA data.

References

1. Crews KR et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clin Pharmacol Ther. 2021;110(4):888-896. PMID: 33368148.
2. Crist RC, Berrettini WH. Pharmacogenetics of OPRM1. Pharmacol Biochem Behav. 2014;123:25-33. PMID: 24220019.
3. Zubieta JK et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240-3. PMID: 12595695.
4. Hwang IC et al. OPRM1 A118G polymorphism and postoperative opioid consumption: a meta-analysis. Anesthesiology. 2014;121(4):825-34. PMID: 25102313.
5. Trescot AM, Faynboym S. A review of the role of genetic testing in pain medicine. Pain Physician. 2014;17(5):425-45. PMID: 25247901.
6. PharmGKB. Codeine and CYP2D6. Clinical Annotation. Available at: https://www.pharmgkb.org/gene/PA128/clinicalAnnotation.

Frequently Asked Questions