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. Author manuscript; available in PMC: 2019 Aug 26.
Published in final edited form as: Cell Rep. 2019 Jul 16;28(3):625–639.e6. doi: 10.1016/j.celrep.2019.06.033

Figure 7. NPY-Y1 Receptor Signaling Determines Sensitivity to Mechanical Itch Stimuli.

Figure 7.

(A) Spontaneous scratching in NPY::Cre; Lbx1FlpO; Tauds-DTR; Ai65ds-tdTom mice 1 week after DT treatment was reduced following injection of NPY (100 μg kg−1, i.p.; n = 9) or the selective Y1 receptor agonist [Leu31, Pro34]-NPY (100 μg kg−1, i.p.; n = 6) when compared with vehicle.

(B) Evoked scratching is reduced when Y1f/f mice (n = 8) but not Lbx1Cre; Y1f/f mice (n = 9) are injected with [Leu31, Pro34]-NPY (100 μg kg−1, i.p., n = 8; vehicle, n = 8).

(C and D) hM3D-mediated activation of the NPY::Cre INs reduces scratching in response to mechanical stimulation of the nape compared with controls (NPY::Cre; Lbx1FlpO; R26ds-hM3D, n = 13; NPY::Cre; R26ds-hM3D controls, n = 11; C) but not when Y1 receptors are inhibited by BIBP 3226 (n = 7; controls, n = 9; D).

(E) Unchanged chloroquine-induced scratching following activation of the NPY::Cre INs (n = 12; controls, n = 12).

(F–H) Activation of NPY::Cre INs reduces sensitivity to von Frey hair (F), brush (G), and pinprick (H) stimulation of the plantar hindpaw (n = 13; controls, n = 11).

(I–K) Activation of NPY::Cre INs does not alter sensitivity to von Frey hair (I), brush (J), and pinprick (K) stimulation following Y1 receptor blockade by BIBP 3226 (n = 9; BIBP 3226-injected controls, n = 7).

(L) Schematic showing proposed dorsal horn circuitry for mechanical and chemical itch. Dyn, dynorphin; Nppb, natriuretic peptide B; NPRA, natriuretic peptide receptor A; PN, projection neuron; Sst2A, Sst 2A receptor. Italics indicate neurotransmitters/neuropeptides.

Two-tailed, paired (A and B) or unpaired (C–K) t tests were used to assess statistical differences. *p < 0.05, **p < 0.01, ***p < 0.001. NS, not significant. Data: mean ± SEM (B–L). See also Figure S7.