Comparative effects of α2δ-1 ligands in mouse models of colonic hypersensitivity

Figure 2 Mouse model of non-inflammatory colonic hypersensitivity and assessment of pregabalin, gabapentin and carbamazepine treatments. A: After colorectal distension (CRD) test, three mother-separated mice are considered non-sensitized (grey circles) as described in material and methods and are excluded from the analysis. Distribution of visceromotor response (VMR) values to CRD test highlights an increased response in sensitized neonatal mother-separated (sensitized NMS) (black circles n = 23) compared to non-handled (NH) (white circles n = 17) mice; B: Assessment of colonic sensitivity in sensitized NMS (black squares n = 23) and non-handled (white circles n = 17) mice displays significant differences between groups for highest distension volumes (60, 80 and 100 μL). Top right insert represents the area under the curve (AUC) between 80 μL and 100 μL; C: Carbamazepine (CBZ) administration (10 and 30 mg/kg s.c.) has no effect on VMR response in neonatal mother-separated mice (NMS : n = 8; NH : n = 6); D: Both doses (30 and 100 mg/kg s.c.) of gabapentin (GBP) have no effect on CHS induced by neonatal maternal separation (NMS: n = 8; NH: n = 6); E: Only the highest cumulative dose (30 mg/kg s.c.) of pregabalin (PGB) induces a VMR reduction in response to CRD in NMS mice (NMS : n = 8; NH : n = 6). ^aP < 0.05; ^bP < 0.01, ^eP < 0.001, Neonatal Mother-separated vs Non-handled ANOVA 2 Way (Animal housing; Volume) followed by Bonferroni post-hoc test for multiple comparisons and ^cP < 0.05 Pre-injection vs Post-injection; ANOVA 2 Way (Treatment; Volume) followed by Bonferroni post-hoc test for multiple comparisons. NMS: Neonatal maternal separation; NH: Non-handled.