Widespread hyperalgesia, characterized by pain sensitivity beyond the primary pain site, is a common yet under-characterized feature across chronic pain conditions, including chronic pancreatitis (CP). In this exploratory study, we identified a candidate neural biosignature of widespread hyperalgesia using high-density electroencephalography (EEG) in patients with chronic low back pain (cLBP). Specifically, stimulus-evoked delta, theta, and alpha oscillatory activity in the bilateral medial orbitofrontal cortex (mOFC) differentiated cLBP patients with widespread hyperalgesia from healthy controls. To examine cross-condition generalizability and advance predictive biomarker development for CP, we applied this mOFC-derived EEG biosignature to an independent cohort of patients with CP. The biosignature distinguished CP patients with widespread hyperalgesia and predicted individual treatment responses to peripherally targeted endoscopic therapy. These preliminary findings provide early support for a shared cortical signature of central sensitization across pain conditions and offer translational potential for developing EEG-based predictive tools for treatment response in CP.

JW is the founder and scientific advisor for Pallas Technologies; the remaining authors have no competing interests to declare.

NCT06267365

National Institutes of Health grant UG3NS135170 (LVD, ZSC, TAG, HGP, JW)

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

We analyzed data from 85 pooled sessions of QST and simultaneous high-density EEG recordings, drawn from two prospective cohort studies. Both studies were approved by the NYU Grossman School of Medicine IRB (8/22/2019, #i19-01088; 9/18/2023, #i23-00766) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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All code and processed data used in this study are available at https://github.com/syhyunpark/mOFC-EEG-biosignature-hyperalgesia. The repository includes scripts and data necessary to reproduce all analyses, figures, and tables presented in this preprint. Data from the CP cohort will be deposited in the NIMH Data Archive as part of our funded study.