Depletion of nociceptors predisposes SCD mice to VOE. (A) Diagram of experimental design. (B) Tail flick assay 4 mo after transplantation confirming the absence of hot sensation in the SCD → Trpv1-Cre; iDTA mice (n = 4/group). (C–F) Number of adherent leukocytes (C), rolling leukocytes (D), and WBC-RBC heterotypic interactions (E) and blood flow rate (F) in in the postcapillary collecting venues of cremaster muscle in SCD → iDTA mice (n = 34 venules from five mice) mice and SCD →Trpv1-Cre; iDTA mice (n = 35 from seven mice) analyzed by intravital microscopy. (G) Survival time of SCD → iDTA mice (n = 5) and SCD → Trpv1-Cre; iDTA mice (n = 7) in TNFα-induced acute vaso-occlusion. (H and I) Percentage of aged neutrophils (H) and absolute number of aged neutrophils (I) in peripheral blood of SCD → iDTA mice (n = 8) and SCD →Trpv1-Cre; iDTA (n = 4) mice. Error bars, mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Data represent at least two independent experiments analyzed using unpaired Student’st test in B–F, H, and I and Mantel–Cox test (log-rank) for the survival analysis in G.