Fig 1.
Scanning and distention protocol.
A barostat bag was inserted into the colorectum and was inflated with baseline (0 mmHg), no distention (0 mmHg), mild (20mmHg), or intense (40 mmHg) distention for 80s. The time interval between two stimuli was 15 min to allow for radiotracer decay. Conditions were in random order, but baseline was always first. CRH (2μg/kg) or placebo was then injected and same distention protocol was repeated. Radioactive H2[15O] was injected at bag inflation and then the PET scan was acquired. Blood sampling and ordinate scales for subjective symptoms were measured immediately after each stimulation. Column: baseline, no distention, 20 mmHg or 40 mmHg stimulation.
Fig 2.
Regions showing significant activation changes.
(Left) IBS patients showed significantly more activity than controls in the right amygdala at baseline after CRH injection compared with that at baseline before CRH injection. (Right) Controls showed significantly greater activation than IBS patients in the right amygdala at intense distention after CRH injection compared with saline injection than IBS patients. Results are shown rendered on a single-subject MRI template with axial sections using the threshold PFWE-corrected < 0.05 (voxel level, ROI analysis).
Table 1.
Effect of CRH on brain activation in response to colonic distentions.
Fig 3.
Effects of CRH on the hypothalamic-pituitary-adrenocortical axis.
(A) Plasma ACTH (pg/ml) at baselines between before and after CRH injection in controls with CRH (n = 8) and IBS patients with CRH (n = 8). iv, intravenous injection. Results represent mean ± SD. †P < 0.05, compared with each baseline, paired t-test. (B) A significant drug effect and drug × distention interaction in plasma ACTH (pg/ml) during random distention after drug injection was noted between controls with saline (n = 8), IBS patients with saline (n = 8), controls with CRH (n = 8) and IBS patients with CRH (n = 8), analyzed by GEE. (C) Serum cortisol (μg/ml) at baselines between before and after CRH injection. †P < 0.05, compared with each baseline. (D) Serum cortisol (μg/ml) during random distention after drug injection had a significant drug effect, drug × distention interaction and drug × distention × group interaction by GEE analysis.
Fig 4.
Effects of CRH on the noradrenaline responses.
(A) Increased basal levels of plasma noradrenaline (pg/ml) were found in IBS patients. IBS patients also showed a significant CRH response compared with basal levels between before and after CRH injection. iv, intravenous injection. Results represent mean ± SD. *P < 0.05, independent samples t-test between controls with CRH (n = 8) and IBS patients with CRH (n = 8). †P < 0.05, compared with each baseline, paired t-test. (B) Plasma noradrenaline (pg/ml) responses during random distention after CRH or saline injection between controls with saline (n = 8), IBS patients with saline (n = 8), controls with CRH (n = 8) and IBS patients with CRH (n = 8) showed significant group effect, drug × distention interaction and drug × distention × group interaction by GEE analysis.