The central neuroanatomical correlates of visceral pain in irritable bowel syndrome: An activation -likelihood estimation meta-analysis of functional neuroimaging studies

In irritable bowel syndrome (IBS), chronic visceral pain without underlying abdominal disease is the main symptom causing repeated in-hospital treatment and resulting in reduced quality of life in 5-10% of the general population. The multifactorial pathophysiology of visceral pain in IBS can be explained within the concept of visceral hypersensitivity in which biopsychological stressors lead to a reduced sensory threshold by the mechanism of central sensitization in predisposed individuals. This can be measured psychophysically with balloon distension experiments in which IBS is associated with both the sensation of pain induced by normally non-painful stimulus intensity (allodynia) and a subjectively stronger pain sensation compared to healthy controls (hyperalgesia). Visceral pain can be characterized by sensory-discriminative and affective-motivational qualities correlating with the activation of distinguishable neuronal pathways which can be visualized using functional neuroimaging. An ALE (activation likelihood estimation) meta-analysis including a total of 32 studies with balloon distention experiments during either PET or fMRI was performed to demonstrate the neuroanatomical correlates of visceral pain in IBS. ALE maps for patients with IBS and healthy controls were calculated separately and a contrast analysis between both groups was conducted. The ALE meta-analysis was performed using the GingerAle software version 3.0.2 and was displayed with the Mango software version 4.1 on an anatomical MNI template. Experimentally induced visceral pain correlated with bilateral activation in the thalamus, the insula, the cingulate cortex and the right postcentral gyrus inferior parietal lobe in healthy controls. For patients with IBS, bihemispheric activation of the insula and medio-frontal gyrus/cingulate cortex, left thalamus and parahippocampal gyrus/amygdala was observed. Contrast analysis revealed statistically significant stronger activation of the bilateral thalamus, the left insula, the right inferior parietal lobe/postcentral gyrus and the right precentral gyrus/inferior frontal gyrus in healthy controls. Patients with IBS showed stronger activation of the bilateral insula, the left superio-medial frontal gyrus, the left inferior frontal gyrus and the left parahippocampal gyrus/amygdala. Conjoint analysis showed statically significant overlapping activation in the bilateral insula and left thalamus. This ALE meta-analysis substantiates the idea of two distinguishable neuronal pathways of pain processing. The observed activity patterns are consistent with an enhanced sensitivity to pain in patients with IBS which is associated with neuronal activation in the insula and cingulate cortex. Visceral hypersensitivity may therefore be related to a sensitization of the homeostatic-autonomous pathway of pain processing resulting from convergence of peripheral input as well as cognitive and emotional modulation.