Chronic administration of the sGC stimulator, VL-102, produces both acute and chronic mechanical hyperalgesia in the hindpaw. C57Bl/6J mice were treated every second day with different doses of VL-102 (0-1 mg/kg, ip) for 9 days. (A) Basal responses, as assessed prior to vehicle or VL-102 administration, significantly decreased in groups receiving 0.1 and 1 mg/kg, starting from day 3 onwards (p<0.01), and in 0.01 mg/kg treated animals on days 7 and 9 (p<0.05). p<0.001 effect of dose, time and interaction, 2-way RM ANOVA and Holm-Sidak post-hoc analysis. (B) VL-102 produced significant mechanical hyperalgesia in mice tested 2 hours post-drug or vehicle administration. p<0.01 effect of dose and time, and interaction, 2-way RM ANOVA and Holm-Sidak post-hoc analysis. n=6-12/group. (C) Basal mechanical responses, as assessed prior to vehicle or VL-102 (0.01 and 1 mg/kg, IP) treatment, significantly decreased in the VL-102 group during the treatment period, and took 5 days to recover following the final VL-102 injection. For 1 mg/kg p<0.001 effect of drug, time and interaction, for 0.01 mg/kg p<0.01 effect of drug and time only; 2-way RM ANOVA and Holm-Sidak post-hoc analysis. **p<0.01, n=6/group. Stimulation of soluble guanylyl cyclase causes basal hypersensitivity and acute hyperalgesia.