Tac2 Mutant mice did not exhibit defects in pain and itch sensation. A: In situ hybridization analyses of wildtype and mutant spinal cords using Tac2 and somatostatin antisense probes demonstrated the loss of Tac2 expression in mutant mice, while the expression of the somatostatin neuropeptide gene was unaffected. B-I: Responses to nociceptive and pruritic stimuli were normal in homozygous Tac2-Cre mice. Mutant (mut) Tac2-Cre mice were indistinguishable from wildtype (wt) littermates in terms of latency of hindpaw withdrawal upon application of various noxious temperatures (B, p = 0.19, 0.33, 0.09, 0.71, 0.39, 0.40; 3 female controls, 3 male controls, 4 female mutants, 3 male mutants); in mechanical threshold for eliciting hindpaw withdrawal following application of graded pressure by von Frey fibers (C, p = 0.48; 12 female controls, 7 male controls, 9 female mutants, 12 male mutants), and to the tail by the Randall-Selitto apparatus (D, p = 1.0; 3 female controls, 2 female mutants, 2 male mutants). Licking and biting responses to hindpaw formalin injections were unaffected in the first phase, the first 10 minutes post-injection, and the second phase, 10-60 minutes post-injection (E, p = 0.32; 4 female controls, 3 male controls, 5 female mutants, 2 male mutants). Furthermore, there was no significant difference in itch-related scratching responses following administration at the indicated dosages of pruritic agents including Compound 48/80 (F, p = 0.65; 4 female controls, 1 male control, 4 female mutants, 4 male mutants); PAR2 agonist (G n = 8; p = 0.29; 8 female controls, 8 male controls, 8 female mutants, 8 male mutants); Chloroquine (H, p = 0.64; 4 female controls, 4 female mutants, 3 male mutants); and Me-5-HT (I, p = 0.33; 8 female controls, 8 male controls, 8 female mutants, 8 male mutants).