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A recurrent neural network model of chronic pain development and recovery

Huang, K.; Marmor, G.; van der Molen, T.; Zhang, Z.; Gicqueau, P.; Reveles, J.; Morrissey, K.; Tang, J.; Lu, L.; Ilmi, K.; Lue, J.; Barba Zuniga, G.; Miller, M. B.; Kosik, K. S.; Yang, H.; Santander, T.; Bullo, F.; Hansma, P. K.

2026-04-22 neuroscience
10.64898/2026.04.18.719337 bioRxiv
Show abstract

Chronic pain presents a leading challenge in the world today for both clinicians and researchers. Because chronic pain is difficult to explain and treat, it is often managed with opioids despite providing limited relief and contributing to dependence and misuse. Persistent pain can be maintained by altered central nervous system processing even in the absence of distinct tissue damage or disease, which may limit the efficacy of conventional pharmacological therapies that target nociceptive signal transmission rather than maladaptive central nervous system dynamics often present in those with chronic pain. Although neuroimaging studies have identified this shift from nociceptive to emotional circuits during pain chronification, a quantitative framework linking these neural changes to longitudinal pain trajectories or recovery is lacking. We present a parsimonious firing-rate model that can account for the development of and recovery from chronic pain, which is based on the theoretical framework established by Wilson and Cowan. The model provides a quantitative explanation of how sensitization, anxiety, and fear maintain pain even after an injury has healed, and how calming stimulus downregulates these processes to facilitate recovery. A study applying the same principles as the model produced an average pain decrease of 3.5 on the Visual Analog Scale (VAS), with all subjects experiencing a reduction in pain. These results, coupled with our model and findings in prior studies, suggest that increasing calming stimulus can reduce pain without necessitating pharmacological or invasive, resource-intensive interventions.

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