Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls

Abstract

Background and aims: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI).

Patients and methods: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal).

Results: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain.

Conclusions: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.

Figure 1

Differences in rectal distension pain ratings (0 = no pain, 10 = unbearable pain) with and without painful heterotopic ice water immersion of the foot in 10 healthy subjects and five constipated (IBS-C) and five diarrhoeic (IBS-D) irritable bowel syndrome (IBS) patients. Negative values denote decreased rectal pain with heterotopic stimulation. Medians, interquartile ranges, and total ranges of repeated two distensions are shown. **p<0.01, healthy subjects versus IBS-C and IBS-D.

Figure 2

Schematic representation of the main volumes of interest (VOI) defined for the functional magnetic resonance imaging analysis (top). Abbreviations: fsup, superior dorsolateral prefrontal cortex; finf, inferior dorsolateral prefrontal cortex; amyg/hipp, amygdala and hippocampus; insa, anterior insula; insp, posterior insula; smrg, secondary sensory cortex; occ, occipital visual cortex; paracen, primary sensory cortex; thal, thalamus; cingp, posterior cingulate cortex; cinga, anterior cingulate cortex. Significantly increased or decreased activations during painful rectal distension without (middle row) or with (bottom row) painful heterotopic stimulation of the foot compared with baseline are shown in healthy controls, and constipated (IBS-C) and diarrhoeic (IBS-D) irritable bowel syndrome (IBS) patients. VOIs significantly activated or deactivated compared with baseline within each group are shaded in pink and light blue, respectively. Significant activations or deactivations compared with other subject groups are depicted in red or dark blue, respectively. For detailed results of all activated VOIs, please refer to table 2 ▶.

Figure 3

Functional magnetic resonance imaging in a representative healthy control, and a constipated (IBS-C) and diarrhoeic (IBS-D) irritable bowel syndrome (IBS) patient during painful rectal distension without (top row) and with painful heterotopic stimulation (bottom row) at sections through the anterior cingulate (A) and insula (B). The anterior cingulate and insula cortices are encircled. Clusters with significant differences from baseline are depicted as colour coded values (see z scale bar).

Figure 4

Averaged functional magnetic resonance imaging time courses (BOLD signal change) for right inferior prefrontal (R inf prefrontal) volumes of interest, right anterior insula (R ant insula), and the left visual cortex (L visual, control region) in healthy controls, and constipated (IBS-C) and diarrhoeic (IBS-D) irritable bowel syndrome (IBS) patients. Black bars mark balloon inflation. Responses to rectal balloon inflation without (left graph) and with (right graph) heterotopic stimulation are shown. Note delay of BOLD responses due to both haemodynamic delay and time needed to inflate/deflate the balloon.