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Papers of the Week

Papers: 15 Apr 2023 - 21 Apr 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

2023 Apr 03



Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.


Weinrich JA, Liu CD, Jewell ME, Andolina CR, Bernstein MX, Benitez J, Rodriguez-Rosado S, Braz JM, Maze M, Nemenov MI, Basbaum AI


The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain’s negative affect. Here, using imaging of neuronal calcium dynamics in mice, we report that nitrous oxide, a general anesthetic that reduces pain affect, paradoxically, increases ACC spontaneous activity. As expected, a noxious stimulus also increased ACC activity. However, as nitrous oxide increases baseline activity, the relative change in activity from pre-stimulus baseline was significantly less than the change in the absence of the general anesthetic. We suggest that this relative change in activity represents a neural signature of the affective pain experience. Furthermore, this signature of pain persists under general anesthesia induced by isoflurane, at concentrations in which the mouse is unresponsive. We suggest that this signature underlies the phenomenon of connected consciousness, in which use of the isolated forelimb technique revealed that pain percepts can persist in anesthetized patients.