Fig. 2.

(A) PS was infused into the bladder and 24 hours later, we observed a significant increase in the number of withdrawal responses to suprapubic stimulation in vehicle-treated rats (n = 7) compared with sham controls (n = 5). (B) In rats (n = 7), pretreatment with linaclotide for 7 days significantly decreased the average withdrawal response frequencies to suprapubic stimulation compared with vehicle-treated animals. (C) An increase in colonic sensitivity was shown as an exaggerated visceromotor response to CRD in vehicle-treated rats (n = 9) compared with sham controls (n = 9). (D) Pretreatment with linaclotide for 7 days (n = 9) reversed the effect of PS-induced colonic hypersensitivity, as shown in the significant reduction of the visceromotor response to CRD. Data are expressed as the mean ± S.E.M. Statistical significance was determined using two-way repeated-measures ANOVA followed by a Bonferroni post-test. **P < 0.01; ***P < 0.001; ****P < 0.0001 (compared with sham controls plus vehicle); ^†P < 0.05; ^††P < 0.01; ^††††P < 0.0001 (compared with PS plus vehicle). LIN, linaclotide; VEH, vehicle.