Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.
Jarret Ap Weinrich, Cindy D Liu, Madison E Jewell, Christopher R Andolina, Mollie X Bernstein, Jorge Benitez, Sian Rodriguez-Rosado, Joao M Braz, Mervyn Maze, Mikhail I Nemenov, Allan I. Basbaum
bioRxiv : the preprint server for biology April 3, 2023 preprint DOI: 10.1101/2023.04.03.534475 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (in vivo imaging in mice) |
|---|---|
| Population | Mice |
| Interventions | Nitrous oxide Isoflurane |
| Key findings | Nitrous oxide increases baseline ACC activity, reducing the relative stimulus-evoked change, which the authors propose as a neural signature of affective pain. This signature persists under isoflurane anesthesia, potentially explaining connected consciousness. |
Abstract
The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain's negative affect. Here, using in vivo 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.