J Neurogastroenterol Motil.  2016 Oct;22(4):558-574. 10.5056/jnm16001.

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

• Farzaei MH
• Bahramsoltani R
• Abdollahi
• Rahimi R

• KMID: 2433449
• DOI: http://doi.org/10.5056/jnm16001

Abstract

Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH.

Keyword

Hyperalgesia; Irritable bowel syndrome; Pain perception; Pain; visceral; Visceral hypersensitivity

MeSH Terms

Abdominal Pain
Central Nervous System
Gonadal Steroid Hormones
Humans
Hyperalgesia
Hypersensitivity*
Irritable Bowel Syndrome*
Ligands
Pain Perception
Pathology
Phosphotransferases
Receptors, Adrenergic
Receptors, Cannabinoid
Receptors, Glutamate
Receptors, Opioid
Receptors, Proteinase-Activated
Receptors, Serotonin
Tachykinins
Tyrosine
Visceral Pain
Gonadal Steroid Hormones
Ligands
Phosphotransferases
Receptors, Adrenergic
Receptors, Cannabinoid
Receptors, Glutamate
Receptors, Opioid
Receptors, Proteinase-Activated
Receptors, Serotonin
Tachykinins
Tyrosine