Where does nociplastic pain hitch a ride in the amygdala?

Open paper intelligence

In TRAP2 mice, inflammation-tagged parabrachial (elPB) neurons project most densely to posterior capsular central amygdala (pCeC) and form strong synapses with pain-tagged pCeC cells; exciting those CeA neurons recreates bilateral hindpaw sensitization.

Source

The posterior capsular central amygdala showing synaptic coactivation with nociplastic pain-associated parabrachial neurons in mice

Okuda T, Uchiyama S, Sato N, et al. · iScience · 2025

doi.org/10.1016/j.isci.2025.113001 Read the full paper ↗4 citationscc by

Study at a glance

Design: Animal / in-vitro — fosTRAP2 mouse circuit study of nociplastic pain: activity-dependent tagging, optogenetics, and chemogenetics of elPB–CeA neurons after transient inflammation
N: N=9 · Multiple TRAP2 experiments; slice physiology example TRAPed n=39 cells from M=9 mice; tracing/chemogenetics used additional animals
Population: Transgenic TRAP2 (fosTRAP2) mice after transient localized (upper-lip) inflammation
Outcome: Whether pain-tagged elPB neurons synaptically co-activate posterior capsular CeA (pCeC) neurons that drive nociplastic sensitization

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

After transient localized inflammation, they used fosTRAP2 mice to express ChR2-YFP, markers, and DREADDs in pain-activated neurons, then mapped elPB projections, recorded pCeC synapses, and chemogenetically/optogenetically tested behavior.

What they found

NociTRAPed elPB neurons projected widely but most densely to CeA, especially caudal capsular CeA (pCeC, about −1.4 to −1.9 mm from bregma), with robust synapses onto nociTRAPed pCeC neurons. Exciting nociTRAPed CeA neurons reproduced bilateral hindpaw sensitization without ongoing nociceptor drive.

The limits

What it doesn't show

Mouse lip-inflammation TRAP does not prove this circuit is the sole cause of human fibromyalgia-type nociplastic pain, and tagging is activity-history based, not a complete cell-type census.

Key terms

Nociplastic pain: Heightened pain without nociceptor activation or nerve injury; modeled here after transient inflammation.
elPB: External lateral parabrachial nucleus, a major ascending nociceptive relay to CeA.
pCeC: Posterior (caudal) capsular central amygdala, proposed as the co-activation site.
TRAP2 / nociTRAPed: fosTRAP2 activity tagging of neurons that fired during the inflammatory pain window.
ChR2-YFP: Light-gated channel used to map and stimulate pain-tagged axons/cells.
DREADDs: Chemogenetic receptors used to excite nociTRAPed CeA neurons in behaving mice.

Flashcards

1 / 10

Research intelligence for this paper

See its role on concept claims, tensions it is part of, placement history, and related discoveries.

Open paper intelligence

Quiz yourself

1 / 5

Nociplastic pain means:

Common questions

What mice?

fosTRAP2 mice after transient localized inflammation.

Where do tagged elPB axons concentrate?

Most densely in CeA, especially posterior capsular CeA (pCeC).

What happens if tagged CeA cells are excited?

Bilateral hindpaw sensitization is reproduced.

pCeC coordinates?

About −1.4 to −1.9 mm from bregma.