Figures & data
Figure 1 Induction of acute visceral hypersensitivity. Infusion of dilute acetic acid into the rat colon (i.c.) (n=7) increased colonic sensitivity quantified as an increase in the number of abdominal contractions when compared to saline controls (n=7). Data are expressed as mean ± SEM. Statistical significance was determined using Two-Way Repeated Measure ANOVA followed by a Bonferroni post-test: ####p<0.0001, compared to Saline control.
Figure 2 Effect of HM01 (1, 3, 10, 30 mg/kg, p.o.) (n= 4–6/group) on acetic acid (AA) induced visceral hypersensitivity. (A) Administration of HM01 reversed the colonic hypersensitivity as shown by the significant reduction of the visceral motor response (VMR) to colorectal distention (CRD). (B) In a separate cohort of animals, administration of ghrelin antagonist H0900 (30 mg/kg, p.o.) reversed the antinociceptive effects of HM01 (1.0 mg/kg, p.o.) (n=7). Data are expressed as mean ± SEM. Statistical significance was determined using Two-Way Repeated Measure ANOVA followed by a Bonferroni post-test: *p<0.05, **p<0.01, ***p<0.001, compared to AA+Vehicle; +p<0.05, compared to AA+HM01+H0900.
Figure 3 Effect of ipamorelin (IPAM) (0.01, 0.1, 1.0 mg/kg, i.v.) (n= 4–6/group) on acetic acid (AA) induced visceral hypersensitivity. (A) Administration of IPAM (1.0 mg/kg, i.v.) reversed the colonic hypersensitivity as shown by the significant reduction of the visceral motor response (VMR) to colorectal distention (CRD). (B) In a separate cohort of animals, administration of ghrelin antagonist H0900 (30 mg/kg, p.o.) reversed the antinociceptive effects of IPAM (1 mg/kg, i.v.) (n=7). Data are expressed as mean ± SEM. Statistical significance was determined using Two-Way Repeated Measure ANOVA followed by a Bonferroni post-test ***p<0.001, ****p<0.0001, compared to AA+Vehicle; ++p<0.01, +++p<0.001 compared to AA+IPAM+H0900.
Figure 4 Effects of HM01 and ipamorelin (IPAM) on acetic acid (AA) induced increased somatic hypersensitivity. (A) Rats that received colonic acetic acid infusion (n=9) had a significantly decreased in withdrawal threshold to probing with the von Frey filament when compared to rats receiving colonic saline infusions (n=9). Treatment with HM01 (1.0 mg/kg, p.o.) (n=9) restored the withdrawal threshold, whereas administration of the selective ghrelin antagonist H0090 (30 mg/kg, p.o.) (n=9) reversed the antinociceptive effects of HM01. (B) Rats that received colonic acetic acid infusion (n=9) had a significantly decreased in withdrawal threshold to probing with the von Frey filament when compared to rats receiving colonic saline infusions (n=9). Treatment with IPAM (1.0 mg/kg, i.v.) (n=9) significantly increased the withdrawal threshold, whereas administration of the selective ghrelin antagonist H0090 (30 mg/kg, p.o.) (n=9) reversed the antinociceptive effects of IPAM. Data are expressed as mean ± SEM. Statistical significance was determined using One-Way ANOVA followed by a Tukey’s multi-comparisons post-test, ####p<0.0001 compared to Saline; ***p<0.001, ****p<0.0001 compared to AA+Vehicle, ++p<0.01, ++++p<0.0001 compared to AA+HM01+H0900 or AA+IPAM+H0900.
