Fig. 2
From: Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking
Loss of EndoA2 in sensory neurons inhibits touch and mechanical allodynia. a Tamoxifen (TAM)-inducible EndoA2 knockout in sensory neurons was generated by crossing EndoA2fl/fl mice to AvCreERT2 mice. The EndoA2fl/fl and EndoA2fl/fl × AvCreERT2 mice received 150 mg/kg TAM intraperitoneal injection (i.p.) for 5 d. Somatosensory behavioral assays were performed on mice 7–21 d after TAM injections. b The percentage of withdrawal for von Frey filaments under various forces in EndoA2fl/fl and EndoA2fl/fl × AvCreERT2 mice after TAM injection. n = 12. ##P < 0.01, ###P < 0.001 compared with EndoA2fl/fl group. The behaviors of EndoA2fl/fl and EndoA2fl/fl × AvCreERT2 mice were evaluated by cotton (c), back tape (d) and foot tape (e) tests after TAM injection. n = 12. The effects of EndoA2 knockout in sensory neurons on the punctate and dynamic mechanical allodynia induced by SNL (f–h), CFA (i–k) and VCR (l–n). n = 8–9. o Schematic of the CPA device and experimental design. The dark chamber is labeled A, and the bright chamber is labeled B. The amounts of time that mice spent in the dark A chamber during 15-min periods on Day 1 and Day 6 were measured. On Days 2–5, the mouse was placed in the indicated chamber for 20 min, with or without punctate, dynamic, and Hargreaves stimulation. p The effect of deletion of EndoA2 in DRG neurons on the CPA scores induced by punctate training in SNL mice (the CPA score was defined as the difference in the amount of time that the mice stayed in the dark A chamber before and after training: pre–post). n = 6. q The effect of deletion of EndoA2 in DRG neurons on the CPA scores induced by dynamic training in SNL mice. n = 6. The effect of deleting EndoA2 in DRG neurons on the CPA scores induced by punctate (r) and dynamic (s) training in CFA mice. n = 6. Two-tailed independent Student’s t test (c–e, p–s); Two-way ANOVA followed by Bonferroni’s multiple comparisons test (b, g, h, j, k, m, n). *P < 0.05, **P < 0.01, ***P < 0.001, ns non-significant. The error bars indicate the SEMs. EndoA2 endophilin A2, TAM tamoxifen, SNL spinal nerve ligation, CFA complete Freund’s adjuvant, VCR vincristine, CIPN chemotherapy-induced peripheral neuropathy