Light your candles and cross your fingers

And CCK-8S application at the lPAG enhances pain sensitivity

When we activate these CCK+ ACC projections at the lPAG, we can detect increased mechanical sensitivity.

When we silenced CCK-expressing ACC projections at the lPAG, this disrupted the enhanced pain in both the social and conditioned models

We asked what regions send CCK projections into the lPAG, and through retrograde tracing in CCK-Cre mice we found this awesome set of long-range ACC neurons that send projections to the lPAG.

And we found that antagonizing CCK receptors at the lPAG but not the dmPAG blocks the enhanced pain in both paradigms

We chose to look at the effect of miroinfusing the CCK antagonist at the dmPAG and lPAG because, according to the beautiful micrographs from Bandler and Shipley 1994, these two regions send projections to the descending pain circuit through the RVM (Credit to PMID: 7817403)

Interestingly, a greater number of cells are activated in the intermediate PAG in pain-expecting mice compared to the anterior-most PAG region and a very posterior PAG region from bregma. The PAG is usually treated as a singular blob, so this is a really cool aspect of the study.

We show that a systemic antagonist of cholecystokinin (CCK) receptors blocks the expectation of pain, whether the source of the enhanced expectations of pain was a social source or an environmental source.

We independently developed two mouse models of nocebo hyperalgesia, one a social source (often studied as emotional contagion or social fear learning) and one a conditioned source of information enhancing expectations of pain.