Table 1.

Summary of epigenetic changes involved in visceral hypersensitivity and the effects of pharmacological treatment in rodent models.

Location	Epigenetic modification	Species	Sex	Model	Effect	Downstream gene expression	Pharmacology to reverse visceral hypersensitivity	Ref
Amygdala	DNA methylation	Rat	Male	Repeated WAS	↑GR methylation, ↓CRH methylation	↓GR, ↑CRH	HDAC inhibitor TSA i.c.v.	109
	Histone acetylation	Rat	Male	CORT implant	↓GR promotor acetylation	↓GR	HDAC inhibitor TSA intra-amygdala	110
Spinal cord	miRNA	Rat	Female	Neonatal cystitis	↑miR181a & miR181b	↓GABAAα−1	/	111
		Rat	Female	Neonatal cystitis	↑miR-92–3p	↓KCC2, ↓VGAT	miR-92 lentivirus i.t.	112
	Histone acetylation	Rat	Both	Prenatal + adult HeICS	↑H3 acetylation @BDNF promoter	↑BDNF	BDNF siRNA i.t. HAT inhibitor curcumin p.o. HAT inhibitor anacardic acid i.t.	105
		Rat	Male	Neonatal + adult TNBS	↑H3K9 & H3K12 acetylation @BDNF promoter	↑BDNF	HAT inhibitor garcinol i.t.	113
		Rat	Female	Forced swim test	↓Acetylation mGlu2/3 promoter	↓mGlu2/3	HDAC inhibitor SAHA i.t.	114
		Rat	Male	Maternal separation	↓Global H4K12 acetylation	/	HDAC inhibitor SAHA i.p.	119
DRG	miRNA	Rat	Male	TNBS	↓miR-199a	↑TRPV1	mir-199a lentivirus i.p.	120
	DNA methylation	Rat	Male	Repeated WAS	↑GR, CNR1 methylation	↓GR, ↓CNR1	DNMT1 siRNA i.t.	121
	Histone acetylation	Rat	Male	Repeated WAS	↑TRPV1 acetylation	↑TRPV1	/	121

Downward arrows indicate a decrease whereas upward arrows indicate an increase in epigenetic modifications or gene expression levels. / indicates not examined in the study. Pharmacological inhibitors were infused directly into the targeted area. DRG, dorsal root ganglia; miRNA, microRNA; WAS, water avoidance stress; CORT, corticosterone; HeICS, heterotypic intermittent chronic stress; TNBS, trinitrobenzenesulfonic acid; GR, glucocorticoid receptor; CRH, corticotropin-releasing hormone; H3, histone 3; BDNF, brain derived neurotrophic factor; H3K9, lysine 9 on histone 3; H3K12, lysine 12 on histone 3; mGlu2/3, group II metabotropic glutamate receptor; H4K12, lysine 12 on histone 4; CNR1, cannabinoid receptor 1; TRPV1, transient receptor potential cation channel subfamily V member 1; GABA_Aα−1, gamma-aminobutyric acid type A receptor alpha1 subunit; KCC2, Solute carrier family 12 member 5; VGAT, vesicular GABA transporter; HDAC, histone deacetylase; TSA, trichostatin A; HAT, histone acetyltransferase; SAHA, suberoylanilide hydroxamic acid; DNMT1, DNA methyltransferase 1; siRNA, small interfering RNA