(A) Administration i.t. of ALKAL2 (1 μM) promotes thermal hyperalgesia, which is reversed by the administration of lorlatinib (ALKAL2, n = 9; ALKAL2+lorlatinib, n = 8). Statistical analysis was performed using 2-way ANOVA followed by Bonferroni’s post hoc test. *P < 0.05; ***P < 0.001. (B) Representative confocal images illustrating pALK induction in the lamina I and II of the spinal dorsal horn following i.t. infusion of ALKAL2. Activation of pALK is reversed by administration of lorlatinib prior to ALKAL2 administration. Scale bars: 100 μm. (C) Bar graph of the pALK signal intensity represented in B in the spinal dorsal horn (control, n = 7; ALKAL2, n = 8; ALKAL2+lorlatinib, n = 6; 1 hour). Statistical analysis was performed using 1-way ANOVA followed by Tukey’s post hoc test. *P < 0.05. Data are represented as mean ± SEM.