Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception.
Natl Sci Rev
; 11(7): nwae195, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-39045468
ABSTRACT
Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEAMOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEAMOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Natl Sci Rev
Year:
2024
Document type:
Article
Affiliation country:
China
Publication country:
CHINA
/
CN
/
REPUBLIC OF CHINA