Early-life stress induces visceral hypersensitivity in mice.
Early-life stress is a risk factor for irritable bowel syndrome (IBS), a common and debilitating functional gastrointestinal disorder that is often co-morbid with stress-related psychiatric disorders. In the rat, maternal separation (MS) stress has been shown to induce visceral hypersensitivity in adulthood and thus has become a useful model of IBS. However, development of mouse models of maternal separation has been difficult. Given the advent of transgenic mouse technology, such models would be useful to further our understanding of the pathophysiology of IBS and to develop new pharmacological treatments. Thus, the present study aimed to develop a mouse model of MS stress-induced visceral hyperalgesia as measured using manometric recordings of colorectal distension (CRD). Moreover, since the GABA(B) receptor has been reported to play a role in pain processes, we also assessed its role in visceral nociception using novel GABA(B(1b)) receptor subunit knockout mice. CRD was performed in adult male wildtype and GABA(B(1b)) receptor knockout mice that had undergone unpredictable MS combined with unpredictable maternal stress (MSUS) from postnatal day 1 through 14 (PND 1-14). MSUS induced visceral hypersensitivity in both wildtype and GABA(B(1b)) receptor knockout mice when compared with non-stressed mice. Wildtype and GABA(B(1b)) receptor knockout mice did not differ in baseline or stress-induced visceral sensitivity. To the best of our knowledge, this is the first study to show that early-life stress induces visceral hypersensitivity in a mouse model. These findings may provide a novel mouse model of visceral hypersensitivity which may aid our understanding of its underlying mechanisms in future studies.
Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork, Ireland.
Rachel D
RD
Moloney
Olivia F
OF
O'Leary
Daniela
D
Felice
Bernhard
B
Bettler
Timothy G
TG
Dinan
John F
JF
Cryan
D000818:Animals; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D018345:Mice, Knockout; D018080:Receptors, GABA-B / Q000235:genetics; D013315:Stress, Psychological / Q000150:complications*; D059265:Visceral Pain / Q000209:etiology*
D018080:Receptors, GABA-B