Research program
Nociplastic Pain: Phenotyping and Genetics
What shapes shared susceptibility across chronic pain phenotypes?
Our pain research focuses on nociplastic mechanisms and shared susceptibility across chronic pain conditions. We bring together statistical genetics, electronic health record (EHR) phenotyping, and patient-reported data.
Three mechanisms of pain
Nociceptive, neuropathic, and nociplastic pain describe different mechanistic contributions that can coexist and cut across clinical diagnoses.
| Mechanism | What it means |
|---|---|
| Nociceptive | Pain arising from peripheral nociceptor activation in response to actual or threatened damage to non-neural tissue. |
| Neuropathic | Pain attributable to a lesion or disease of the somatosensory nervous system. |
| Nociplastic | Pain involving altered nociception when nociceptive or neuropathic mechanisms do not adequately account for the pain. |
Definitions follow the International Association for the Study of Pain’s terminology.
Nociplastic mechanisms and overlapping pain conditions
Fibromyalgia and other chronic overlapping pain conditions motivate a view of pain that spans conventional diagnostic boundaries. Amplified sensory processing and altered pain modulation may contribute to these presentations alongside condition-specific mechanisms. This perspective, reviewed by Fitzcharles et al. (2021), informs our interest in shared and distinct genetic contributions across pain phenotypes.
Our work within the Chronic Pain & Fatigue Research Center
Our lab is part of the University of Michigan’s Chronic Pain & Fatigue Research Center, where we collaborate with Daniel Clauw, Sawsan As-Sanie, Andrew Schrepf, and Stephan Frangakis.
Within this shared research setting, our lab contributes statistical genetics and EHR analysis, alongside our collaborators’ clinical and mechanistic expertise.
Dan Clauw’s longstanding work on fibromyalgia and central pain amplification has helped shape our approach to nociplastic pain. His emphasis on mechanisms that extend beyond local pathology provides a conceptual foundation for studying pain across diagnostic categories. Dan and our CPFRC colleagues discuss this perspective in U-M’s overview of nociplastic pain.
Where genetics and phenotyping fit
We are interested in how inherited variation relates to pain susceptibility and overlap across conditions. Phenotype definition is central to this work: diagnostic codes, reported symptoms, and longitudinal clinical records capture different aspects of pain.
We consider ascertainment, care patterns, and cohort differences when interpreting genetic associations. These questions connect our pain collaborations with the lab’s broader work in biobank research and statistical genetics.
Our team
Current work
Projects and collaborations
Pain and women's health
ActiveEndometriosis-associated pelvic pain mechanisms
The project examines whether differences in brain structure and connectivity are related to pelvic pain that persists after endometriosis treatment.
Sawsan As-Sanie and Andrew Schrepf are the principal investigators.
Pain research training
ActiveU-M HEAL PAIN Cohort Program
The U-M HEAL PAIN T90/R90 Cohort Program provides research training and mentoring for early-career chronic pain researchers.
Daniel Clauw, Kelley McLain Kidwell, and Jenna Wiens are the principal investigators.
Publications
Selected papers
Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions
Brain
Why it matters: Combining all chronic pain locations into one phenotype can obscure important biological differences. Genetic contributions were stronger for multisite than single-site pain; nine of 23 multisite loci replicated in HUNT, while functional genomics and brain imaging pointed toward axonogenesis and corticolimbic circuitry. The results also depend on how researchers define the pain phenotype.
Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia
Pain
Why it matters: No single assay is likely to capture all of the biology underlying fibromyalgia. Across patient cohorts, flow cytometry, blood transcriptomics, genetic analyses, and skin biopsy each pointed toward altered natural killer (NK) cell biology, including NK cells near peripheral nerves. Together, the findings support further study of a possible role for NK cells, but they do not show that NK cells cause fibromyalgia.