biostudies-literatureIvy ZKNHLBI NIH HHSNCI NIH HHS1918-1927https://www.ebi.ac.uk/biostudies/studies/S-EPMC10731576biostudies-literatureUnknown142(22)Vaso-occlusive pain episodes (VOE) cause severe pain in patients with sickle cell disease (SCD). Vaso-occlusive events promote ischemia/reperfusion pathobiology that activates complement. We hypothesized that complement activation is linked to VOE. We used cold to induce VOE in the Townes sickle homozygous for hemoglobin S (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 Frey filaments applied to the plantar surface of the hind paw to assess mechanical hyperalgesia in HbSS and control Townes mice homozygous for hemoglobin A (HbAA) mice after cold exposure at 10°C/50°F for 1 hour. Cold exposure induced more vaso-occlusion in nonhyperalgesic HbSS mice (3BloodCold exposure induces vaso-occlusion and pain in sickle mice that depend on complement activation.PMC10731576T32 HL007062R01 HL114567R01 CA241627R01 HL147562R01 CA263777Khasabova IAJuliette JPKhasabov SGChen CBeckman JDIvy ZKBelcher JDNguyen JRogness VMTaylor RPAllen KSimone DAVercellotti GMAbdulla FRuan CGupta KfalseCold exposure induces vaso-occlusion and pain in sickle mice that depend on complement activation.Vaso-occlusive pain episodes (VOE) cause severe pain in patients with sickle cell disease (SCD). Vaso-occlusive events promote ischemia/reperfusion pathobiology that activates complement. We hypothesized that complement activation is linked to VOE. We used cold to induce VOE in the Townes sickle homozygous for hemoglobin S (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 Frey filaments applied to the plantar surface of the hind paw to assess mechanical hyperalgesia in HbSS and control Townes mice homozygous for hemoglobin A (HbAA) mice after cold exposure at 10°C/50°F for 1 hour. Cold exposure induced more vaso-occlusion in nonhyperalgesic HbSS mice (32023-01-01T00:00:00Z2023 Nov2025-04-18T16:02:20.893Z2025-04-07T03:02:46.469ZS-EPMC107315763777436910.1182/blood.2022019282