Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome

Abstract

Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls (p < 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.

Figure 1.

Trial design. In each session, 20–30 moderate intensity rectal distentions (15 s at 45 mmHg) were randomly intermingled with an equal number of mild distentions (25 mmHg) and sham distentions (5 mmHg).

Figure 2.

Group functional activation maps. BOLD responses (p < 0.01) within the ROIs (outlined in yellow) in female IBS-C patients and healthy controls in response to the cue light and the subsequent 5 (sham), 25, and 45 mmHg distentions are superimposed on a structural MRI representative of MNI space for a sagittal slice 5 mm from the midline in each hemisphere (left side, left hemisphere), a coronal slice 6 mm behind the anterior commissure, and a transaxial slice through the anterior commissure. All figures depict neurological orientation (left = left).

Figure 3.

Covariation of negative affect with anticipatory BOLD response. Higher BOLD signal during the cue period (less deactivation) was directly correlated with negative affect (p < 0.01; shown in red) in LCC-PBN (location of crosshairs) and left amygdala (for anger and stress), depicted within an MNI space sagittal slice 4 mm to the right of the anterior commissure and a transaxial slice 24 mm inferior to the anterior commissure.

Figure 4.

Covariation of LCC-PBN anticipatory BOLD response with BOLD response during visceral distention. Cue-related deactivation of LCC-PBN (blue circle) was associated with greater activation (p < 0.01; shown in green) during subsequent 45 mmHg distention in ACC and right, but not left, OFC. Coordinates of slices depicted: L ACC (x = −6; y = 34), R ACC (x = 6; z = −4), R OFC (x = 36; y = 42).