A model of painful vaso-occlusive crisis in mice with sickle cell disease

In order to better understand mechanisms underlying acute pain during vaso-occlusive crises (VOCs) in patients with sickle cell disease, Khasabova et al report on a clinically relevant model in mice where VOC is stimulated by exposure to cold. Cold exposure produces robust hyperalgesia, stasis, hypoxia, elevated heart rate, and increased levels of the endocannabinoid 2-AG and its synthesizing enzyme, DAGLβ, in plasma and blood cells, respectively. Blocking DAGLβ prevents the development of hyperalgesia. Collectively, these data point to 2-AG signaling as a targetable mediator of VOC pain.