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 Ͻ 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.

Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: A network analysis

“…In particular, consistent reports of sex-related differences in amygdala responses have been reported during anticipation of aversive emotional stimuli in healthy subjects (Buchel et al, 1998;Cahill, 2006;Mackiewicz et al, 2006;Sarinopoulos et al, 2006) and IBS patients (Berman et al, 2008;Naliboff et al, 2003) and amygdala activity is associated with the cognitive and affective modulation of pain (Carrasquillo and Gereau, 2007;Neugebauer et al, 2004).…”

Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging

“…[12][13][14][15]18 Furthermore, resting state fMRI study performed on IBS patients demonstrated increased spontaneous neuronal activity in visceral afferent processing regions, while decreased regional brain activity in cognitive and pain regulatory regions. 21 To date, most neuro-imaging studies performed in response to visceral pain among IBS patients have been carried out in Western countries and female patients [10][11][12][18][19][20][22][23][24][25][26][27][28][29] (Table 1). However, in some Asian countries including India, a large proportion of patients with IBS are males.…”

Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain

“…The pivotal finding from these studies indicated that the central mechanisms mediating the stress-induced phenotypes following chronic intermittent psychological stress involved increased CRF, particularly in limbic brain regions (Myers and Greenwood-Van Meerveld, 2012;Tran et al, 2013). Limbic brain regions of IBS patients, including the amygdala and extended amygdala, exhibit hyperactivity in response to stress, negative effect, and colorectal stimuli when compared with controls (Berman et al, 2008;Bonaz et al, 2002). Interestingly, when IBS patients were challenged with vascular infusions of CRF, there was a greater activation of the extended amygdala in response to colorectal stimuli, suggesting an important role for CRF-mediated mechanisms in the extended amygdala in IBS pathophysiology (Tanaka et al, 2011).…”