Manipulation of receptor tyrosine kinase-like orphan receptor ROR2 in the spinal cord regulates pain behaviours and neuronal sensitisation. (a) Validation of ROR2 small interfering RNA (siRNA) transfection efficiency in vivo. ***P<0.001, n=6. (b and c) effect of ROR2 siRNA (10 μg in 0.5 μl) on development of CCI-induced thermal hyperalgesia (b) and mechanical allodynia (c). **P<0.01, ***P<0.001, Scramble siRNA-Sham vs Scramble siRNA-CCI; #P<0.05, ##P<0.01, ###P<0.001, Scramble siRNA-CCI vs ROR2 siRNA-CCI; n=8. (d and e) Effect of ROR2 siRNA (10 μg in 0.5 μl) on maintenance of CCI-induced thermal hyperalgesia (d) and mechanical allodynia (e). **P<0.01, ***P<0.001, Sham-Scramble siRNA vs CCI-Scramble siRNA; #P<0.05, ##P<0.01, ###P<0.001, CCI-Scramble siRNA vs CCI-ROR2 siRNA; n=8. (f and g) Fos expression after intrathecal injection of ROR2 siRNA (10 μg in 0.5 μl) or scramble siRNA in CCI mice; representative immunocytochemical staining is shown in (f) and quantitative data are shown in (g). Dotted lines in the above behaviour test figures indicate Fos evaluation times. *P<0.05, ***P<0.001, n=6. (h) Tyrosine phosphorylation of ROR2 after spinal administration of Wnt5a (0.5 μg in 0.5 μl). *P<0.05, ***P<0.001, n=6. (i and j) Effect of Wnt5a (0.5 μg in 0.5 μl) on the thermal hyperalgesia (i) and mechanical allodynia (j) in naïve mice. **P<0.01, ***P<0.001, Scramble siRNA-Saline vs Scramble siRNA-Wnt5a; #P<0.05, ##P<0.01, ###P<0.001, Scramble siRNA-Wnt5a vs ROR2 siRNA-Wnt5a; n=8. (k) Fos expression after intrathecal injection of Wnt5a (0.5 μg in 0.5 μl) or saline in naïve mice. Fos was assessed 2 h after Wnt5a injection. ***P<0.001, n=6.