Effects of NB001 and gabapentin on irritable bowel syndrome-induced behavioral anxiety and spontaneous pain

Mol Brain. 2014 Jun 16;7:47. doi: 10.1186/1756-6606-7-47.

Abstract

Irritable bowel syndrome (IBS) is characterized by recurrent abdominal discomfort, spontaneous pain, colorectal hypersensitivity and bowel dysfunction. Patients with IBS also suffer from emotional anxiety and depression. However, few animal studies have investigated IBS-induced spontaneous pain and behavioral anxiety. In this study, we assessed spontaneous pain and anxiety behaviors in an adult mouse model of IBS induced by zymosan administration. By using Fos protein as a marker, we found that sensory and emotion related brain regions were activated at day 7 after the treatment with zymosan; these regions include the prefrontal cortex, anterior cingulate cortex, insular cortex and amygdala. Behaviorally, zymosan administration triggered spontaneous pain (decreased spontaneous activities in the open field test) and increased anxiety-like behaviors in three different tests (the open field, elevated plus maze and light/dark box tests). Intraperitoneal injection of NB001, an adenylyl cyclase 1 (AC1) inhibitor, reduced spontaneous pain but had no significant effect on behavioral anxiety. In contrast, gabapentin reduced both spontaneous pain and behavioral anxiety. These results indicate that NB001 and gabapentin may inhibit spontaneous pain and anxiety-like behaviors through different mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / administration & dosage
  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / pharmacology
  • Adenosine Triphosphate / therapeutic use
  • Amines / administration & dosage
  • Amines / pharmacology
  • Amines / therapeutic use*
  • Animals
  • Anxiety / complications*
  • Anxiety / drug therapy
  • Behavior, Animal* / drug effects
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / pharmacology
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Gabapentin
  • Injections, Intraperitoneal
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pain / complications*
  • Pain / drug therapy
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Up-Regulation / drug effects
  • Visceral Pain / complications
  • Visceral Pain / drug therapy
  • Zymosan / pharmacology
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • 5-((2-(6-Amino-9H-purin-9-yl) ethyl) amino)-1-pentanol
  • Amines
  • Cyclohexanecarboxylic Acids
  • Proto-Oncogene Proteins c-fos
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Adenosine Triphosphate
  • Zymosan