Fig. 1: Opioid-induced itch is mediated by MOR on the NPY+ interneurons.

A In situ hybridization RNAscope images of MOR mRNA (Oprm1, white) and NPY mRNA (Npy, red) in mouse spinal dorsal horn (SDH). Yellow arrows indicate Oprm1 double-labeled with Npy, cells containing ≥ 5 RNAscope puncta were considered positive expression. Scale bar = 20 μm. B The percentage of co-expression between MOR and NPY neurons in the SDH, 12 spinal cord sections from 6 mice were analyzed. C Time course (left) and total scratch bouts (right) following intrathecal injection 10 nmol CNO (30 min before) and 0.3 nmol morphine in NpyCre;hM3Dq or WT mice, student’s unpaired two-tailed t-test. D Time course (left) and total scratch bouts (right) after intrathecal injection of 0.1, 0.3, 1 nmol morphine in NpyCre;Oprm1fl/fl mice, two-way ANOVA, Bonferroni’s multiple comparisons. E Time course (left) and total scratch bouts (right) after intrathecal injection of various doses of EM-1 (0.3, 1, 3, 10 nmol) in WT mice. One-way ANOVA, Dunnett’s multiple comparisons. F Intrathecal EM-1 (10 nmol)-induced scratching was significantly inhibited in NpyCre;Oprm1fl/fl mice, student’s unpaired two-tailed t test. Data are shown as means ± SEM. P values are indicated in the figures. Sample sizes are presented in parentheses. Source data are provided as a Source Data file. Created in BioRender. Wang, Z. (2025) https://BioRender.com/u0x7q3a.