Early-life stress induces visceral hypersensitivity in mice

Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork, Ireland.
Neuroscience Letters (Impact Factor: 2.03). 03/2012; 512(2):99-102. DOI: 10.1016/j.neulet.2012.01.066
Source: PubMed


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.

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    • " ; Lippmann et al . 2007 ; Aisa et al . 2008 ; Gareau et al . 2008 ; Oines et al . 2012 ) , anxiety - like behaviour ( Varghese et al . 2006 ; Lippmann et al . 2007 ; Desbonnet et al . 2010 ; O ' Mahony et al . 2011 ; Abelaira et al . 2013 ; Li et al . 2013 ) , visceral hypersensitivity ( Eutamene et al . 2007 ; O ' Mahony et al . 2011 ; Moloney et al . 2012 ; Felice et al . 2014 ) and altered cholinergic activity in the gut ( Gareau et al . 2007b ; O ' Malley et al . 2010 ) accompanied by increased intestinal permeability ( Söderholm et al . 2002 ; Barreau et al . 2004a ; García - R ´ odenas et al . 2006 ; Eutamene et al . 2007 ; Gareau et al . 2007b ; Oines et al . 2012 ) . Maternally sep"
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    The Journal of Physiology 04/2014; 592(14). DOI:10.1113/jphysiol.2014.273995 · 5.04 Impact Factor
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    • "Previous animal studies have demonstrated that acute and chronic stress is associated with the development of allodynia, hyperalgesia or unaltered nociceptive sensitivity [17,18,39,40]. For example, 10–20 min forced swimming daily for 3 days induces hyperalgesia to thermal and chemical stimuli 8 to 9 days after the last swim session [17]. "
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    Molecular Pain 07/2013; 9(1):35. DOI:10.1186/1744-8069-9-35 · 3.65 Impact Factor
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    • "Besides a small effect of developmental fluoxetine on ipsilateral PWT at 8 weeks, we did not find any significant effect of prenatal stress and/or developmental fluoxetine exposure on basal nociceptive thresholds to mechanical and thermal stimuli in juvenile and adult male offspring. Although these parameters were previously not specifically investigated, research has shown that basal hypersensitivity in response to mechanical stimulation of muscles or viscera can occur in adult offspring following repeated postnatal stress, via maternal separation or exposure to limited bedding material [6], [52], [53]. The impact of SSRIs during development on basal sensory thresholds has not been widely investigated. "
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    PLoS ONE 02/2013; 8(2):e57608. DOI:10.1371/journal.pone.0057608 · 3.23 Impact Factor
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