An action networks model for pain reveals cortical neuromodulation targets

Chronic neuropathic pain is a debilitating condition, difficult to treat, and associated with poor outcomes, including addiction and suicide. Neuromodulation of primary motor cortex and dorsolateral prefrontal cortex (dlPFC) alleviates neuropathic pain in some cases, though the mechanism remains unknown. Recent advances in functional MRI led to the identification of the Somato-Cognitive Action Network (SCAN) within the primary motor cortex, and Action Mode Network (AMN) represented in the dlPFC. Both networks are important for pain perception, suggesting the previously baffling analgesic effects of motor cortex stimulation were likely due to modulation of action-relevant pain signals in these newly recognized networks. Inter-individual differences in SCAN and AMN provide a plausible explanation for the varied effectiveness of current neuromodulation targeting methods for chronic pain. Our novel action feedback-loop pain-control model suggests that personalized, precision targeting of the AMN and SCAN will improve chronic pain management, paving the way for future neuromodulatory treatments.