Altered brain activation to colorectal distention in visceral hypersensitive maternal‐separated rats

Abstract

Early life trauma can predispose to increased visceral pain perception. Human neuroimaging studies emphasize that altered brain processing may contribute to increased visceral sensitivity. The aim of our study was to evaluate brain responses to painful visceral stimuli in maternal-separated rats before and after acute stress exposure in vivo. H(2)(15)O microPET scanning was performed during colorectal distention in maternal-separated rats before and after water avoidance stress. Brain images were anatomically normalized to Paxinos space and analyzed by voxel-based statistical parametric mapping (SPM2). Colorectal induced visceral pain was assessed by recording of the visceromotor response using abdominal muscle electromyography. Colorectal distention (1.0-2.0 mL) evoked a volume-dependent increase in visceromotor response in maternal-separated rats. Stress [water avoidance (WA)] induced an increased visceromotor response to colorectal distention in awake and anesthetized rats. In pre-WA rats, colorectal distention evoked significant increases in regional blood flow in the cerebellum and periaquaductal gray (PAG). Colorectal distention post-WA revealed activation clusters covering the PAG as well as somatosensory cortex and hippocampus. At maximal colorectal distention, the frontal cortex was significantly deactivated. WA stress induced increased pain perception as well as activation of the somatosensory cortex, PAG, and hippocampus in maternal-separated rats. These findings are in line with human studies and provide indirect evidence that the maternal separation model mimics the cerebral response to visceral hypersensitivity in humans.