Cold exposure induces vaso-occlusion and pain in sickle mice that depend on complement activation

Vaso-occlusive pain episodes (VOE) cause severe pain in sickle cell disease (SCD) patients. Vaso-occlusive events promote ischemia/reperfusion (I/R) pathobiology that activates complement. We hypothesized that complement activation is linked to VOE. We used cold to induce VOE in the Townes sickle (HbSS) mouse model and complement inhibitors to determine whether anaphylatoxin C5a mediates VOE. We used a dorsal skinfold chamber to measure microvascular stasis (vaso-occlusion) and von …