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Papers of the Week

Papers: 7 Sep 2019 - 13 Sep 2019

Animal Studies


2019 Sep 10

Cell Rep



Editor's Pick

A Midbrain Circuit that Mediates Headache Aversiveness in Rats.


Waung MW, Margolis EB, Charbit AR, Fields HL
Cell Rep. 2019 Sep 10; 28(11):2739-2747.e4.
PMID: 31509737.


Migraines are a major health burden, but treatment is limited because of inadequate understanding of neural mechanisms underlying headache. Imaging studies of migraine patients demonstrate changes in both pain-modulatory circuits and reward-processing regions, but whether these changes contribute to the experience of headache is unknown. Here, we demonstrate a direct connection between the ventrolateral periaqueductal gray (vlPAG) and the ventral tegmental area (VTA) that contributes to headache aversiveness in rats. Many VTA neurons receive monosynaptic input from the vlPAG, and cranial nociceptive input increases Fos expression in VTA-projecting vlPAG neurons. Activation of PAG inputs to the VTA induces avoidance behavior, while inactivation of these projections induces a place preference only in animals with headache. This work identifies a distinct pathway that mediates cranial nociceptive aversiveness.