Published online Jun 14, 2013. doi: 10.3748/wjg.v19.i22.3487
Revised: May 15, 2013
Accepted: May 22, 2013
Published online: June 14, 2013
AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity.
METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/nucleobindin-2 (NUCB2), 50 μg of α-helical corticotropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made.
RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05).
CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, which may be implicated in brain CRF/CRF1 signaling pathways.
Core tip: This is a well conducted experimental study on the possible effect of nesfatin-1 in visceral hypersensitivity. Currently no reports have been published concerning the role of nesfatin-1 in irritable bowel syndrome (IBS). In a well-established visceral hypersensitivity animal model, we found an elevated nesfatin-1 level in the serum, and there was a reduction in evoked abdominal electromyography and abdominal withdrawal reflex scores after treatment with nesfatin-1 antibody, a non-selective corticotropin releasing factor (CRF) receptor antagonist, or a selective CRF1 receptor antagonist. These results suggest that nesfatin-1 may be associated with visceral hypersensitivity in model rats and implicated in brain CRF/CRF1 signaling pathways, which contribute to the visceral hypersensitivity of IBS.