Send to

Choose Destination
Neurogastroenterol Motil. 2015 Dec;27(12):1831-6. doi: 10.1111/nmo.12675. Epub 2015 Sep 25.

Early-life stress-induced visceral hypersensitivity and anxiety behavior is reversed by histone deacetylase inhibition.

Author information

Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork, Cork, Ireland.
Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.


Stressful life events, especially in childhood, can have detrimental effects on health and are associated with a host of psychiatric and gastrointestinal disorders including irritable bowel syndrome (IBS). Early-life stress can be recapitulated in animals using the maternal separation (MS) model, exhibiting many key phenotypic outcomes including visceral hypersensitivity and anxiety-like behaviors. The molecular mechanisms of MS are unclear, but recent studies point to a role for epigenetics. Histone acetylation is a key epigenetic mark that is altered in numerous stress-related disease states. Here, we investigated the role of histone acetylation in early-life stress-induced visceral hypersensitivity. Interestingly, increased number of pain behaviors and reduced threshold of visceral sensation were associated with alterations in histone acetylation in the lumbosacral spinal cord, a key region in visceral pain processing. Moreover, we also investigated whether the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could reverse early-life stress-induced visceral hypersensitivity and stress-induced fecal pellet output in the MS model. Significantly, SAHA reversed both of these parameters. Taken together, these data describe, for the first time, a key role of histone acetylation in the pathophysiology of early-life stress-induced visceral hypersensitivity in a well-established model of IBS. These findings will inform new research aimed at the development of novel pharmaceutical approaches targeting the epigenetic machinery for novel anti-IBS drugs.


SAHA; epigenetics; histone acetylation; irritable bowel syndrome; stress; visceral pain

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center