Graphs are replotted with data sorted into male (blue) and females (red). (A–C) There were no significant sex differences following intramedullary microinjection of saline or SP for histamine- (A, n=9, SP: F1,7 = 11.49 p=0.0116, Sex: F1,7 = 4.325 p=0.0761, SP*Sex: F1,7 = 1.682 p=0.2357) or chloroquine-evoked scratching (B, n=9, SP: F1,7 = 5.64 p=0.0493, Sex: F1,7 = 2.094 p=0.1911, SP*Sex: F1,7 = 1.969 p=0.2033), or for thermal withdrawal latencies (C, n=8, SP: F1,6 = 0.153 p=0.7092, Sex: F1,6 = 2.208 p=0.1878, SP*Sex: F1,6 = 0.7851 p=0.4097). (D) Males exhibited a significantly higher mechanical withdrawal threshold following intramedullary saline ($, n=10, SP: F1,8 = 84.72 p = <0.001, Sex: F1,8 = 31.28 p=0.005, SP*Sex: F1,8 = 2.599 p=0.1456), while both sexes showed a significant reduction in withdrawal threshold following intramedullary SP. (E) Suppression of histamine-evoked scratching following clozapine was significantly greater in males (#; n=14, Clozapine: F1,12 = 49.73 p = <0.0001, Sex: F1,12 = 1.84 p=0.2, Clozapine*Sex: F1,12 = 21.6 p=0.0006). (F–H) There were no sex differences for chloroquine-evoked scratching (F, n=15, Clozapine: F1,13 = 22.09 p=0.0004, Sex: F1,13 = 0.1533 p=0.7018, Clozapine*Sex: F1,13 = 0.5548 p=0.4696), thermal withdrawal latency (G, n=15, Clozapine: F1,13 = 1.921 p=0.844, Sex: F1,13 = 0.0403 p=0.844, Clozapine*Sex: F1,13 = 0.6736 p=0.4266) or mechanical withdrawal threshold (H, n=15, Clozapine: F1,13 = 0.006799 p=0.9355, Sex: F1,13 = 1.51 p=0.2409, Clozapine*Sex: F1,13 = 1.116 p=0.3101). (I–L) We did observe a higher number of histamine-evoked scratch bouts in female mice when compared to male -(I, $, n=9, Clozapine: F1,7 = 0.5241 p=0.4926, Sex: F1,7 = 10.74 p=0.0135, Clozapine*Sex: F1,7 = 2.429 p=0.1631) and a higher mechanical withdrawal threshold for female versus male mice (L, $, n=10, Clozapine: F1,8 = 0.1487 p=0.7099, Sex: F1,8 = 8.878 p=0.0176, Clozapine*Sex: F1,8 = 1.671 p=0.2322). In the Hargreaves test there was no significant effect of clozapine administration or sex on thermal withdrawal latency, but we did observe a significant interaction (K, n=10, Clozapine: F1,8 = 0.3303 p=0.5813, Sex: F1,8 = 0.0842 p=0.7791, Clozapine*Sex: F1,8 = 6.277 p=0.0366). We did not observe any sex differences for chloroquine- evoked scratch bouts (J, #, n=10, Clozapine: F1,8 = 0.147 p=0.4061, Sex: F1,8 = 0.00381 p=0.9523, Clozapine*Sex: F1,8 = 0.147 p=0.7114),.