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

What Decode Shows You

Find out why you needed more medication after surgery, or why pain hits harder for you. Decode analyzes four genes — OPRM1, COMT, BDNF, and ANKK1 — 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. We also explain the well-established CYP2D6 link to codeine and tramadol response — but CYP2D6 needs a specialized caller a consumer DNA array doesn't provide, so Decode tells you that honestly rather than invent a result.

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 because of CYP2D6 genetics. Decode cannot call your CYP2D6 status from array data, so for this specific pathway we explain the science and CPIC guidance rather than claim a personal result.
• 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 — OPRM1, the receptor gene Decode analyzes, has been studied mainly for morphine dose requirements; the same receptor binds oxycodone and fentanyl, but the genetic evidence for those is weaker still (see the evidence section below). Codeine, tramadol, and hydrocodone depend on CYP2D6, which Decode cannot call from your raw data — we tell you this directly rather than guess.

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 OPRM1, COMT, BDNF, and ANKK1 and assign genotypes, diplotypes, and phenotype classifications. CYP2D6 cannot be called from a genotyping array, so it is not included in this step.
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) has been studied for its effect on post-operative morphine requirements. The CPIC guideline covering OPRM1 describes the effect as modest — on the order of a 10% increase in some studies for G-allele carriers — and judged the evidence insufficient to support a specific dosing recommendation on its own (Crews et al., 2021; 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 analyzes four genes with clinical evidence for pain sensitivity and analgesic response:

• 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.

What about CYP2D6? CYP2D6 metabolizes codeine, tramadol, hydrocodone, and oxycodone, and is central to why codeine doesn't work for some people. But CYP2D6 needs a specialized caller that a consumer genotyping array does not provide — Decode does not call your CYP2D6 status. Rather than guess, we tell you the truth and point you to CPIC guidance and clinical CYP2D6 testing for codeine- and tramadol-related decisions.

Limitations

• Decode analyzes four genes for pain & anesthesia — OPRM1, COMT, BDNF, and ANKK1. Pain is complex and influenced by many additional genetic and non-genetic factors including inflammation, psychological state, and prior pain history.
• Your key gene CYP2D6 cannot be called from a genotyping array. CYP2D6 needs a specialized caller that a consumer array does not provide, so Decode does not report a CYP2D6 result rather than invent one it cannot support.
• 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 — Check your HLA-DQ2/DQ8 status 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: 33387367.
2. Crist RC, Berrettini WH. Pharmacogenetics of OPRM1. Pharmacol Biochem Behav. 2014;123:25-33. PMID: 24201053.
3. Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Klein T, Leeder JS. Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med. 2017;19(1):69-76. PMID: 27388693.
4. Zubieta JK et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240-3. PMID: 12595695.
5. Hwang IC et al. OPRM1 A118G gene variant and postoperative opioid requirement: a systematic review and meta-analysis. Anesthesiology. 2014;121(4):825-34. PMID: 25102313.
6. Trescot AM, Faynboym S. A review of the role of genetic testing in pain medicine. Pain Physician. 2014;17(5):425-45. PMID: 25247900.
7. PharmGKB. Codeine and CYP2D6. Clinical Annotation. Available at: https://www.pharmgkb.org/gene/PA128/clinicalAnnotation.

Frequently Asked Questions