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Scaling Up Cortical Control Inhibits Pain
Jahrane Dale (New York University), Haocheng Zhou (Central South University, Third Xiangya Hospital), Qiaosheng Zhang (New York University), Erik Martinez (New York University), Sile Hu (NYU Langone Health, New York University), Kevin Liu (New York University), Louise Urien (New York University), Zhe Sage Chen (NYU Langone Health, New York University), Jing Wang (NYU Langone Health, New York University)
Résumé : Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC) is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain.