Fig. 5: Continuing nociceptor activity drives tactile allodynia.

a, Time course of von Frey 50% withdrawal threshold (mean ± s.e.m.) before (time = 0) and after injection of PGE2 into the hind paw of mice with silenced Trpv1-lineage nociceptors (red; n = 6) and littermate controls (black; n = 7). PGE2 injection induced mechanical sensitization in controls but not in mice with silenced nociceptors (P < 0.05) over 60 min. b, Violin-plot analysis of expression level (log-normalized single-cell RNA sequencing data)^11,28 showing selective expression of Htr1f in NP3 nociceptors. c, Percentage and level of activation (ΔAUC) of neurons after injection of the selective HTR1F agonist LY344864 into the cheek. d, Heat maps of DRG imaging for mice expressing GCaMP under the control of Sst-Cre. Responses from 200 neurons of six mice showed that Sst-Cre labelled a population of brush cells and a separate population of LY344864-responsive neurons. Below, quantification of LY344864-stimulated activity (mean sum of transient amplitudes ± s.e.m.) for brush and non-brush cells. e, von Frey 50% withdrawal threshold (mean ± s.e.m.) before (time = 0) and after injection of LY344864 into the hind paw of wild-type mice (magenta; n = 7) and littermates with silenced Trpv1-lineage nociceptors (grey; n = 6). LY344864 injection induced mechanical sensitization in wild-type mice for at least 60 min but was ineffective in mice with silenced nociceptors. f, von Frey 60% withdrawal thresholds (mean ± s.e.m.; n = 7) at baseline (grey) and after paw injection of LY344864 in mice expressing KORD⁵³ in Trpv1-lineage nociceptors. Mice received intraperitoneal dimethylsulfoxide (vehicle; magenta) or the selective KORD ligand Salvinorin B (SalB; blue) immediately before paw injection of LY344864. See Supplementary Tables 1 and 2 for full details of statistical tests and numbers; *P < 0.05; **P < 0.01. Scale bar, 10 s.