Cutaneous mechanical hypersensitivity results from enhanced TRPV1, not TRPA1, function. (A) Representative recordings of mechanically evoked action potentials in HbSS mice treated with vehicle (0.1% N-methyl-2-pyrrolidone [NMP]; top), a TRPA1 antagonist (100μM HC-030031; middle), and a TRPV1 antagonist (10μM A-425619; bottom). Action potential waveforms are presented on the right. (B) Acute treatment of receptive fields of C fibers from HbSS mice with the TRPV1 antagonist A-425619 substantially reduced the response to mechanical force to control levels (***P < .0001; repeated measures 2-way ANOVA). (C) Vehicle for A-425619 had no effect on the mechanical response of C fibers from HbSS mice (P > .05). (D) The TRPV1 antagonist A-425619 had no effect on the C fiber response to mechanical force in HbAA control mice, indicating that the TRPV1 inhibition effect was selective for sickle cell–induced mechanical sensitization (P > .05). (E) The TRPA1 antagonist HC-030031 had no effect on the mechanical firing in C fibers from HbSS mice (P > .05).