Figure 1. Mechanical Pain Defects Do Not Arise from DRG or Brain.

(A) Cartoon of Avil^Cre mice showing Cre (red) is restricted to primary afferents.

(B) All DRG neurons express tomato in lsl-tdTom;Avil^Cre mice.

(C) VGLUT3-IR is not detected in primary afferents (arrows) of VGLUT3^fl/fl;Avil^Cre in the adult.

(D) Paw withdrawal thresholds (PWT) of VGLUT3^fl/fl;Avil^Cre mice do not differ from control mice after carrageenan (n=12 both groups) or SNI (n=7 and n=9 respectively). Randall-Selitto thresholds also do not differ from controls (n=8 and n=6 respectively).

(E) Cartoon of Hoxb8^Cre mice showing Cre (red) is expressed by spinal cord and DRG neurons, but not brain.

(F) VGLUT3^fl/fl;Hoxb8^Cre mice lack VGLUT3-IR in the dorsal horn at p10.

(G) VGLUT3-IR is still present in the striatum of VGLUT3^fl/fl;Hoxb8^Cre mice.

(H) PWTs of VGLUT3^fl/fl;Hoxb8^Cre mice are significantly greater than controls after carrageenan (n=11 and n=9 respectively) and SNI (n=9 and n=4 respectively). Randall-Selitto thresholds are also significantly elevated compared to controls (n=9 and n=7).

(I) Cartoon of KRT14^Cre mice showing Cre (red) is restricted to keratinocytes and Merkel cells.

(J) As expected, tomato and the Merkel cell marker TROMA1-IR co-localize (arrowhead) in hindpaw glabrous skin of lsl-tdTom;KRT14^Cre mice.

(K) Tomato and TROMA1-IR also co-localize (arrowheads) in hindpaw glabrous skin of lsl-tdTom;VGLUT3^Cre mice.

(L) PWTs do not differ between VGLUT3^fl/fl;KRT14^Cre and control mice before or after carrageenan (n=10 and n=6 respectively) or SNI (n=3 both groups). Randall-Selitto thresholds also do not differ (n=7 and n=6 respectively).

All scale bars = 100 μm except in G (50 μm). Data are mean ± SEM. *p < 0.05, **p ≤ 0.01, ***p ≤ 0.001.