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

Ming-Ming Zhang,Yun-Qing Li,Ting Zhang,Kohei Koga,Min Zhuo,Shui-Bing Liu,Tao Chen

doi:10.1186/1756-6606-7-47

Ming-Ming Zhang, Yun-Qing Li + Show 5 more

Open Access

https://doi.org/10.1186/1756-6606-7-47

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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.

Highlights

Visceral pain occurs after mechanical or chemical stimulation in and around the internal organs
Zymosan increases the expression of Fos protein in the central nervous system First, we sought to determine whether Irritable bowel syndrome (IBS) activates sensory and emotion related brain areas
In the present study, we examined the neurobehavioral manifestations of zymosan-induced colitis in mice and the effects of NB001 and gabapentin on mice treated with zymosan

Summary

Introduction

Visceral pain occurs after mechanical or chemical stimulation in and around the internal organs. This form of pain is vague and poorly localized [1,2,3,4]. Recent studies indicate that an enhanced primary sensory afferent derived from the colorectum maintained IBS-related pain and Cortical and subcortical areas, such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), insular cortex and amygdala, are important for processing pain, discomfort and emotional responses [16,17,18,19,20,21,22,23]. Calcium-stimulated adenylyl cyclase subtype 1 (AC1) plays important roles in pain-related LTP in the ACC as well as in injury-induced plastic changes [33,34,35,36]

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