Fig. 1: EP2 receptor activation in Schwann cells mediates PGE₂-evoked sustained hindpaw mechanical allodynia (allodynia).

a,d, f Dose-dependent non-evoked nociception and b, e, g dose- and time-dependent allodynia after intraplantar (i.pl.) injection of PGE₂, L-902,688 (L-902), butaprost (Buta) or vehicle (Veh) in C57BL/6 J mice (B6) (n = 8 mice/group). c Schematic representation of agonists/antagonists targeting EP2 and EP4 receptors. h Non-evoked nociception and i allodynia after i.pl. PGE₂ (1.5 nmol) or Veh in B6 pretreated with PF-04448948 (PF, 5nmol), BGC 20-1531 (BGC, 5 nmol) or Veh (n = 8 mice/group). j RT-qPCR for Ptger2, Ptger4 Avil and S100 mRNA in mouse dorsal root ganglia (DRG) sciatic and cutaneous Schwann cells (SCs) (DRG and sciatic SCs n = 4, cutaneous n = 3 independent experiments). k, l Representative images of EP2, EP4, NeuN and S100B expression in mouse DRG and sciatic nerve tissue (scale bar: 20 μm) (n = 3 subjects). m Representative images of EP2, EP4 and SOX10 expression in mouse sciatic and cutaneous SCs (n = 3 independent experiments). n–r Non-evoked nociception (left panel) and allodynia (right panel) after i.pl. PGE₂ or Veh in Plp-Cre, Adv-Cre or Control mice infected with AAV for selective silencing of EP4 (-Ptger4) (P1p-Ptger4 or Adv-Ptger4) (n,o) or EP2 (-Ptger2) (P1p-Ptger2 or Adv-Ptger2) (p,q) or with AAV for a scrambled shRNA (Plp-scrambled) (r) (n = 8 mice/group). Data are mean ±  s.e.m. a, d, f, h, n, o, p, q, r 1-way or b, e, g, i, n, o, p, q, r 2-way ANOVA, Bonferroni correction. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. Veh ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001, ^††††P < 0.0001 vs. PGE₂/Veh, Control^/ PGE₂. Source data are provided as a Source Data file.