Low Frequency Oscillations in the Medial Orbitofrontal Cortex Mediate Widespread Hyperalgesia Across Pain Conditions

Widespread hyperalgesia, characterized by pain sensitivity beyond the primary pain site, is common across chronic pain conditions, yet it is unknown if there are shared neural mechanisms that can function as a biosignature for this condition. We used high-density electroencephalography (EEG) to examine noxious stimulus-evoked cortical activity at both disease and disease-free sites in patients with chronic low back pain (cLBP) and chronic pancreatitis (CP). Compared with healthy controls and patients with localized pain, cLBP patients with widespread hyperalgesia exhibited altered delta, theta, and alpha oscillations in the bilateral medial orbitofrontal cortex (mOFC). To test if this neural signature for widespread hyperalgesia is shared across pain conditions, we applied this mOFC-derived neural signature to an independent cohort of CP patients. We found that this signature not only successfully distinguished CP patients with widespread hyperalgesia but also predicted their pain response to peripherally-targeted interventions. These findings suggest that altered mOFC oscillatory responses may reflect a shared neural mechanism of widespread hyperalgesia across chronic pain conditions.