Neuropathic pain develops when nerves are damaged or do not function properly. Unlike pain caused by a cut or an injury, neuropathic pain often persists long after the original damage has occurred. It affects an estimated 7% to 10% of people worldwide, yet diagnosing and treating it remains difficult because doctors largely rely on a patient’s description of their symptoms.

Pain rating scales can be helpful, but they are also influenced by emotional, psychological, and environmental factors. As a result, two people with similar nerve damage may report very different levels of pain, making it challenging to diagnose neuropathic pain accurately and predict which treatments will work best.

Researchers from the Ohio Pain Clinic discuss growing evidence that RNA biomarkers could provide a more objective way to diagnose, classify, and monitor neuropathic pain. They outline how advances in RNA biology and RNA sequencing may eventually support more personalized pain management.

RNA molecules carry important information about how cells are functioning. By examining changes in different types of RNA, researchers can gain insight into the biological processes occurring within nerve cells and immune cells. Several classes of RNA may prove useful as biomarkers, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), RNA editing, and chemical RNA modifications.

The researchers highlight several genes whose activity changes in people with neuropathic pain. Some of these genes are involved in immune system function, while others influence how nerve cells communicate or respond to injury. Together, these molecular signatures may provide a more complete picture of the biological mechanisms responsible for chronic pain.

The researchers also discuss how single-cell RNA sequencing is helping researchers better understand pain at the cellular level. Instead of examining large groups of cells together, single-cell RNA sequencing analyzes individual cells, revealing how specific populations of neurons and immune cells contribute to the development and persistence of neuropathic pain. Resources such as the iPain single-cell atlas are helping researchers map these complex cellular interactions.

Another promising area involves epitranscriptomics, the study of chemical modifications made to RNA molecules after they are produced. The researchers describe how modifications such as m6A methylation may alter the expression of genes involved in pain signaling, potentially contributing to central sensitization, a process in which the nervous system becomes increasingly sensitive to painful stimuli.

Although no RNA-based diagnostic tests for neuropathic pain have yet received FDA approval, the authors describe how rapid, low-input RNA testing technologies could eventually be incorporated into clinical practice. Such tests could help physicians diagnose neuropathic pain earlier, identify biologically distinct patient groups, monitor treatment responses, and evaluate new therapies.

Much of this work remains at the research stage, and the proposed “pain biology score” has not yet been validated in laboratory or clinical studies. Even so, the growing body of evidence suggests that RNA sequencing and other transcriptomic technologies may eventually provide clinicians with objective biological markers that complement traditional pain assessments and support more personalized care for patients living with chronic neuropathic pain.