Figure 6. δOR on MrgprD⁺ sensory neurons is required for mTreg mediated anti-nociception.

(A) Schematic representation of AAV-induced ablation of Oprd1 in the PNS (B-C) or CNS. (B) Nociceptive thresholds of female mice lacking Oprd1 in the PNS after mTreg expansion compared to controls. (C) Anti-nociceptive efficacy of mTreg expansion. (D) No difference in nociceptive thresholds in female mice lacking Oprd1 in the CNS after mTreg expansion compared to controls. (E) Heatmap of row normalized expression from DRG sensory neurons clusters from combined GSE139088 and GSE201653. (F) Proportions of sensory neuron clusters expressing Oprd1 from E. (G) Representative flow cytometry plot of δOR-GFP (green) expression on IB4⁺ MrgprD⁺ DRG sensory neurons compared to cells from non-reporter mice (purple). Overlaid are lymphoid CD45⁺ CD90.2⁺ cells and myeloid CD45⁺ CD11b⁺ cells from the DRG. (H-I) Percent response to 0.008 g von Frey fiber stimulation after SNI in female (H) or male (I) mice conditionally lacking δOR on MrgprD⁺ neurons (pink) or controls (white). (J) Nociceptive thresholds after mTreg expansion in female mice lacking Oprd1 in MrgprD⁺ neurons compared to controls. (K) Anti-nociceptive efficacy of mTreg expansion. SA-LTMR= Slowly adapting low-threshold mechanoreceptor, RA-LTMR= rapidly-adapting low-threshold mechanoreceptor, MrgprD= Mas-related G protein-coupled receptor D, Prop.= proprioceptor, SST: somatostatin, Trpm8= Transient receptor potential cation channel subfamily M member 8, TAM= Tamoxifen, cKO= Conditional KO, ns = not significant, *p<0.05, **p<0.01,***p<0.001.