Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on Genetics & Nerve Health. Browse all Genetics & Nerve Health education

Neuropathic pain — the burning, shooting, or electric-shock sensations that come from damaged or misfiring nerves — affects millions of people and often resists the treatments that work for ordinary pain. Part of what makes it so variable from person to person is genetics. The way your nerves generate and transmit pain signals, and how your brain processes them, is shaped by inherited variation. Understanding those genetic traits can help explain why neuropathic pain differs so widely and why management usually takes a personalized, provider-guided approach.

What makes neuropathic pain different

Unlike the pain of a cut or a bruise, neuropathic pain comes from the nervous system itself — nerves that have been injured, compressed, or altered by conditions like diabetes, shingles, or nerve entrapment. These nerves can fire spontaneously or overreact to normal touch. Because the problem lives in the signaling machinery of the nerves, small differences in the genes that build and regulate that machinery can produce large differences in how much pain someone feels.

SCN9A and the sodium channel that sets pain intensity

One of the most important pain genes is SCN9A, which encodes the Nav1.7 sodium channel found in pain-sensing neurons. Nav1.7 acts like a volume dial for pain signals. Rare gain-of-function variants in SCN9A cause severe inherited pain disorders, while loss-of-function variants can make people unable to feel pain at all. More common SCN9A variants sit between these extremes and are associated with everyday differences in pain sensitivity. For neuropathic pain specifically, SCN9A variation helps explain why some people's damaged nerves fire far more intensely than others'.

COMT and how the brain processes pain

Pain is not just generated at the nerve — it is amplified or dampened in the brain, and the COMT gene plays a major role there. COMT breaks down dopamine and norepinephrine, neurotransmitters involved in mood, stress, and pain modulation. The well-studied Val158Met variant changes how quickly COMT works. People with slower-acting versions often show heightened pain sensitivity and can be more prone to chronic pain conditions. This is why two people with similar nerve damage may report very different pain levels and respond differently to the same strategies.

Other genes and the bigger pain picture

Neuropathic pain is polygenic, meaning many genes each contribute a little. Variants in genes such as GCH1, which affects a signaling molecule involved in pain pathways, and other ion-channel genes add to individual differences. Inflammatory and nerve-growth genes shape how nerves repair and how much ongoing irritation they produce. No single gene determines someone's experience; instead, this genetic tuning combines with the underlying cause of nerve damage to set each person's baseline.

Where genetics fits in management

Genetic testing does not diagnose neuropathic pain and does not tell you which treatment to use — those decisions belong to a qualified provider who can evaluate the cause, examine your nerves, and weigh evidence-based options such as physical therapy, nerve-targeting medications, and lifestyle measures. What genetic insight adds is context about your pain-signaling and processing pathways. The Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights across systems including nerve signaling and inflammation. Bring that context to your provider as one input, not an answer. Genetics is a guide, not a guarantee.

Frequently Asked Questions

Do genes affect how much neuropathic pain I feel?

Yes. Genes like SCN9A shape how strongly pain-sensing nerves fire, and COMT influences how the brain amplifies or dampens pain. These inherited traits help explain why people with similar nerve damage can experience very different pain levels and respond differently to the same management strategies.

Can a genetic test choose my pain treatment?

No. A genetic test does not diagnose neuropathic pain or select medications or doses, and it is not a pharmacogenomic test. It offers pathway-level context about nerve signaling and pain processing. A qualified provider evaluates the cause and recommends evidence-based, individualized management based on your full clinical picture.

Why does neuropathic pain resist normal painkillers?

Neuropathic pain comes from the nervous system's own signaling rather than tissue injury, so ordinary anti-inflammatory or over-the-counter painkillers often help little. It typically responds better to therapies that target nerve signaling itself. A provider can determine the underlying cause and build a management plan suited to that mechanism.

Is neuropathic pain always caused by an identifiable condition?

Often, but not always. Common causes include diabetes, shingles, injury, and nerve compression, yet some cases have no clear trigger. Genetic factors influence susceptibility and intensity in both situations. A qualified provider works to identify any underlying cause, which guides the most effective, evidence-based management approach.

Know your biology before you act on it. The Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights so you can bring a clearer picture of your genetic landscape to a conversation with a qualified provider. Genetics is a guide, not a guarantee — test before you invest in any protocol.

This article is part of the PlexusDx Education Hub. Browse all Genetics & Nerve Health education

The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not diagnose any condition and does not recommend, prescribe, or determine which peptides you should use. Consult a qualified healthcare provider before beginning any peptide protocol or making changes to your care.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.